Vaccine Effectiveness Of Bivalent HPV Vaccination Against Genital HPV Of A Catch-Up Campaign And 12 Years Routine Vaccination For Girls-Only: A Biennial Repeated Cross-Sectional Study

Vaccine Effectiveness Of Bivalent HPV Vaccination Against Genital HPV Of A Catch-Up Campaign And 12 Years Routine Vaccination For Girls-Only: A Biennial Repeated Cross-Sectional Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Vaccine Effectiveness Of Bivalent HPV Vaccination Against Genital HPV Of A Catch-Up Campaign And 12 Years Routine Vaccination For Girls-Only: A Biennial Repeated Cross-Sectional Study Johannes MA Kusters, Maarten F Schim Loeff, Birgit HB Benthem, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4330011/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Oct, 2024 Read the published version in BMC Medicine → Version 1 posted 10 You are reading this latest preprint version Abstract Background The Netherlands is one of few countries worldwide which has used the bivalent HPV vaccine for girls-only for over a decade. This allows assessment of vaccine effectiveness (VE) against female genital HPV DNA-positivity of this vaccine in an observational post-licensing real-world setting. Additionally, it is unclear whether catch-up vaccination campaigns result in similar VE as routine vaccination. Therefore, type-specific and grouped VE were assessed and compared for women who had been eligible for catch-up vaccination at 13–16 years with those who had been eligible for routine vaccination at 12 years. Methods PASSYON is a Dutch biennial repeated cross-sectional (2011-21) study among sexual health clinic clients aged 16–24 years old. Women provided self-collected vaginal samples, questionnaires on demographics and sexual behaviour were administered, and women self-reported HPV vaccination status. Samples were analysed using a PCR-based assay (SPF 10 -LiPA 25 ). Type-specific and grouped VE estimates, adjusted with propensity score stratification, were assessed against genital positivity for 14 HPV-types. VE for targeted and non-targeted genotypes were compared between women who had been eligible for the catch-up and those who had been eligible for routine vaccination. Results The study included 4,488 female participants who had been eligible for HPV vaccination and provided genital swabs (1,561 eligible for catch-up, 2,927 for routine vaccination). Very high VE against genital HPV-16 and HPV-18 was observed (resp. 93.5% and 89.5%) and significant cross-protection against six other genotypes (HPV-31/33/35/45/52/58), varying from 18.0% (HPV-52) to 79.6% (HPV-45). VE estimates were comparable between women who had been eligible for the catch-up campaign and those eligible for routine vaccination: VE HPV-16/18: 92.2% (95%CI: 87.9–94.9) vs. 91.8% (95%CI: 86.0-95.2). Conclusions In real-world settings, the VE of bivalent vaccine is high against targeted genotypes, with cross-protection against 6 other genotypes. Catch-up campaigns up to age 16 years can be as effective as routine vaccination at age 12. This may inform countries considering catch-up campaigns when introducing or extending the use of HPV vaccination within their national immunisation programmes. human papillomavirus vaccine effectiveness prophylactic vaccination bivalent vaccine catch-up campaign observational study propensity score Figures Figure 1 Figure 2 Figure 3 Background Persistent human papillomavirus (HPV) infections could lead to anogenital warts (AGWs) or cancer[ 1 ]. Approximately 5% of new cancer cases worldwide are attributable to HPV, approximately 3-3.5% by genotype HPV-16 alone[ 2 ]. Several prophylactic vaccines are proven to be effective against persistent HPV infections and CIN2 + and are available across the world. All protect against the two most oncogenic genotypes (HPV-16/18), responsible for about 71% of cervical cancers[ 3 ], and some vaccines offer additional protection to two low-risk HPV (lrHPV) genotypes, and to five additional high-risk HPV (hrHPV) genotypes. The bivalent vaccine Cervarix® is targeted against HPV-16 and HPV-18[ 4 ], and has shown cross-protection effectiveness against other hrHPV genotypes[ 5 ]. Post-licencing observational vaccine effectiveness (VE) studies are important after introduction of a vaccine, to understand the effectiveness in real-world settings. Up to date, several observational studies have been conducted to assess the VE for the bivalent vaccine[ 5 ]. However, some of those studies did not assess VE type-specifically[ 6 , 7 ], or were from countries that offered more than one vaccine type at the same time[ 8 , 9 ]. Herd-immunity provided by another HPV vaccine may influence observed VE of the bivalent vaccine. Other observational studies (including from our own group) used mostly data of women vaccinated within a catch-up campaign[ 10 – 14 ]. In catch-up campaigns it is more likely that some girls have become sexually active before receiving a vaccine than in routine vaccination; therefore VE estimates based on catch-up data might not represent VE in routine vaccination settings. Studies comparing catch-up campaign VE with routine vaccination VE are scarce, and are mostly modelling studies rather than observational studies[ 15 – 17 ]. As more countries start HPV vaccination or start gender-neutral vaccination, mostly introduced in combination with catch-up campaigns, this comparison could inform catch-up strategies. Real-world comparisons of effectiveness between catch-up campaigns and routine vaccination are hence needed. Since the introduction of HPV vaccination in the National Immunisation Programme (NIP) of the Netherlands, the bivalent HPV vaccine has exclusively been used. This started with a catch-up campaign in 2009 targeting girls born in 1993–1996[ 18 ], and became part of routine vaccination in 2010, starting with birth cohort 1997. The Netherlands is one of the few countries which started with bivalent HPV vaccination, and has continued doing so for girls-only until 2022. This makes the Dutch setting unique, and suitable for assessing VE of the bivalent vaccine in real-world post-licencing settings. It additionally provides an opportunity to compare VE of the bivalent HPV vaccine between birth cohorts vaccinated in the catch-up campaign and those vaccinated in the routine vaccination programme. In this study we aimed to (1) assess the type-specific and grouped VE of the bivalent HPV vaccine against female genital HPV DNA-positivity during the 12 year girls-only vaccination period. Additionally, (2) we aimed to compare VE between women offered vaccination during the catch-up campaign to those offered vaccination during routine HPV vaccination. Methods and materials Study setting The PApillomavirus Surveillance among Sti clinic YOungsters in the Netherlands (PASSYON) study is a biennial repeated cross-sectional study among young adult sexual health clinic (SHC) clients[ 19 ]. During each study round, for approximately 2 months SHC clients from 10–14 SHCs aged 16–24 years were asked to participate. After signing a written consent, participants were asked to self-collect a genital swab sample for HPV testing. Women were instructed to collect the cervicovaginal swab sample, by inserting a swab (Copan Diagnostics, Italy) about 4 cm into the vagina, until resistance was felt, and to turn the swab around along the walls of the vagina for about 15 seconds. All swabs were placed in a tube with 1 ml universal transport medium (Copan Diagnostics, Italy) immediately after the swab was taken. Additionally, participants were asked to complete a written questionnaire on demographics and sexual behaviour (such as number of sexual partners lifetime and in preceding 6 months, age of sexual debut, and history of STI). Participants also reported whether they had been vaccinated against HPV. Finally, diagnoses from routine STI testing were available for analyses. For the current analyses, data from the second through seventh study round of PASSYON (2011-21) were used, as these study rounds cover the era in which only girls were invited for HPV vaccination. Only women who had been eligible for HPV vaccination were included, based on their year of birth. Having been eligible for HPV vaccination was defined as being born in 1993 or later, as this was the first birth cohort which had been invited for the catch-up vaccination. Other inclusion criteria were provision of a genital swab and having reported HPV vaccination status in the questionnaire. This study was approved by Medical Ethics Committee of the University of Utrecht, The Netherlands (reference number: 08/397). Laboratory methods All cervicovaginal swabs were stored at -20°C until processing. Samples were analysed within 12 months of collection, to ensure the quality of the sample. After thawing and vortexing, 200 µl of the material was used for DNA extraction using the MagnaPure platform (Total Nucleic Acid Isolation Kit, Roche, the Netherlands). Total DNA was eluted in 100 µl elution buffer and 10 µl was used to amplify HPV-DNA with the SPF 10 primer set. HPV-specific amplicons were detected using enzyme-linked immunoassay (HPV-DEIA, DDL Diagnostic Laboratory, the Netherlands). Positive samples were subsequently genotyped with the Line probe assay (HPV-LiPA, DDL Diagnostic Laboratory, the Netherlands), which is able to identify 25 genotypes (6, 11, 16, 18, 31, 33–35, 39, 40, 42–45, 51–54, 56, 58, 59, 66, 68, 70, 74). Statistical analyses The current report is an updated and elaborated follow-up of previous VE reports with data of the PASSYON study[ 11 , 20 , 21 ]. First, study population characteristics were described and compared by vaccination status. Type-specific and grouped genital HPV DNA-positivity prevalence was calculated for unvaccinated and vaccinated (≥ 1 dose) women, separately. Characteristics were also compared between women of birth cohort 1993-6 (these women had been eligible for catch-up vaccination) and women of birth cohort 1997 and later (these women had been eligible for routine vaccination). Finally, characteristics were compared between women who were excluded from the analyses because of missing genital sample or vaccination status, and those included in the analyses. Type-specific and grouped VE estimates were calculated using the relative risk (RR) for genital HPV DNA-positivity comparing vaccinated and unvaccinated women. VE was calculated as 1 minus the RR times 100%. First, unadjusted, crude VE estimates were calculated. Next, VE was calculated based on propensity score (PS) adjusted (see further) RRs. Type-specific estimates were made for the high-risk genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59, and for the low-risk genotypes 6 and 11. We also assessed prevalences of five different HPV groupings, defined as being DNA-positive for at least one of (1) the bivalent vaccine genotypes (HPV-16/18), (2) the cross-protected genotypes as observed previously[ 22 ] and widely reported in other studies (HPV-31/33/45), (3) the cross-protected types found in the current analysis, (4) the hrHPV genotypes covered by the nonavalent vaccine (HPV-16/18/31/33/45/52/58), and finally (5) all hrHPV genotypes (HPV- 16/18/31/33/35/39/45/51/52/56/58/59). These groupings were also used for other estimates in this study To adjust for differences in study population characteristics over the study rounds, and differences between unvaccinated and vaccinated women, PS stratification (also called subclassification) was used[ 23 – 25 ]. PS was calculated as the propensity of having been vaccinated based on study round, geographical location of the SHC, demographics (age, migration background and education), sexual behaviour (currently having a steady partner, history of hormonal anticonception use, number of sexual partners lifetime and in preceding 6 months) and having a history of other STIs. For each VE calculation, strata were created of the total study population based on quintiles of the PS distribution. Having defined strata, we assessed balance in co-variates in each stratum between the vaccinated and unvaccinated groups. If for each covariate the standardised mean difference between vaccinated and unvaccinated was smaller than 0.10, the balance was considered adequate. If this was not reached, a smaller number of strata was used. Within each stratum the RR risk was established using generalised linear regression models with binomial distribution and log link function[ 26 ]. In these models, HPV DNA-positivity was the dependent variable and self-reported vaccination status the independent variable. The overall effect was obtained by pooling the stratum-specific RR’s using stratum specific weights, which are based on the total number of included participants in that stratum. Stratified analyses Four stratified VE analyses were conducted. Stratified analyses were conducted by (1) birth cohort, where we distinguished women who had been eligible for the catch-up campaign (birth cohort 1993–1996, 13–16 years old at eligibility) from women who had been eligible for routine vaccination in the NIP (birth cohort ≥ 1997, 12 years old at eligibility). For women who had been eligible for the catch-up campaign, an additional stratified analysis was conducted: (2) we compared the VE for women who were, to women who were not, sexually active before, or at the same age the vaccine was offered, indicating being potentially sexually active around the time of vaccination. This was based on self-reported age at sexual debut and the age women had been eligible for vaccination based on their year of birth. For assessing generalisability of the VE estimates, VE analyses were conducted (3) stratified by number of sexual partners in the preceding 6 months (two categories, based on median), and (4) by years sexually active (age at inclusion minus age at sexual debut; three categories, based on tertiles). This was done as our study population might have been more sexually active than the general population. To test whether VE across the assessed strata differed, an interaction term between the stratifying variable and vaccination variable was added to the main VE model, to test for effect modification. All stratified analyses were done type-specifically for HPV-16 and HPV-18, and for all HPV-groupings as mentioned above. For each stratum, propensity scores were calculated and PS stratification was executed for that specific stratum. Sensitivity analyses Two sensitivity analyses were conducted. First, First, instead of adjusting for confounding using PS stratification, we adjusted VE estimated with multivariable logistic regression, adjusting for variables associated with vaccination (being study round, age, education, migration background, age at sexual debut, history of STI). All women offered vaccination during the catch-up campaign (birth cohort 1993-6) were offered a three-dose schedule (0, 1 and 6 months). All women of birth cohort 1997–2000 were offered HPV vaccination at age 12 years, in the same three-dose schedule. Women of birth cohort 2001 and later were offered vaccination in a two-dose schedule (0 and 6 months)[ 18 ]. In order to eliminate any potential differences in VE due to different dosing schedules, we performed a sensitivity analysis restricted to women who had been eligible for 3 doses. All analyses were performed using R RStudio (Version 1.3.959) with help of the cobalt and survey packages. For all analyses, statistical significance was defined as p < 0.05. Results Study population In the PASSYON study a total 13,535 adolescents participated, of whom 9,099 were female. Of those, 5,006 women had been eligible for vaccination. As 518 women had not indicated their vaccination status and/or did not provide a genital swab (422 women without reporting vaccination status, 96 without genital swab, eight missed both), these women were excluded (Supplementary table 1 ). Therefore, 4,488 women were eligible for the current analysis. The majority participated in the three study rounds 2017, 2019 and 2021 (75.7%). 34.8% reported to be unvaccinated (n = 1,561) and 65.2% to be vaccinated (n = 2,927) (Table 1 ). Eligible for the catch-up campaign (birth cohort 1993–1996) in our study population had been 2,345 women (54.2%) and eligible for routine HPV vaccination within the NIP (birth cohort ≥ 1997) had been 1,988 women (45.8%) (Table 2 ). The median number of sex partners in the preceding 6 months was 2 (IQR 1–4), 29.9% had a history of an STI (n = 1,332), and 17.4% had a current Chlamydia trachomatis infection (n = 775). More information on study population characteristics can be found in Tables 1 and 2 . Table 1 Characteristics of the female study population of the PASSYON study who had been eligible for HPV vaccination in the Netherlands, by self-reported vaccination status, the Netherlands, 2011–2021 Total Unvaccinated Vaccinated Variable n (%) or median (IQR) n (%) or median (IQR) n (%) or median (IQR) p-value Total 4,488 1,561 2,927 Study round < 0·001 2011 61 (1·4) 35 (2·2) 26 (0·9) 2013 325 (7·2) 139 (8·9) 186 (6·4) 2015 701 (15·6) 264 (16·9) 437 (14·9) 2017 1,122 (25·0) 404 (25·9) 718 (24·5) 2019 1,115 (24·8) 368 (23·6) 747 (25·5) 2021 1,164 (25·9) 351 (22·5) 813 (27·8) Location SHC 0·13 Amsterdam 1,315 (29·3) 456 (29·2) 859 (29·3) Rotterdam 663 (14·8) 231 (14·8) 432 (14·8) Utrecht 469 (10·5) 148 (9·5) 321 (11·0) Northern Netherlands 1 426 (9·5) 157 (10·1) 269 (9·2) Middle Netherlands 2 534 (11·9) 209 (13·4) 325 (11·1) Southern Netherlands 3 1,081 (24·1) 360 (23·1) 721 (24·6) Age (years) 21 (19, 22) 21 (19, 22) 21 (19, 22) 0·68 Age (years) 0·85 16–18 655 (14·6) 224 (14·3) 431 (14·7) 19–21 2,375 (52·9) 822 (52·7) 1,553 (53·1) 22–24 1,458 (32·5) 515 (33·0) 943 (32·2) Migration background < 0·001 None (Dutch) 3,522 (78·8) 1,148 (73·9) 2,374 (81·4) Migrant 257 (5·7) 112 (7·2) 145 (5·0) Child of migrant 692 (15·5) 294 (18·9) 398 (13·6) Education 4 < 0·001 (Pre)university 3,442 (76·8) 1,102 (70·6) 2,340 (80·0) Other 1,042 (23·2) 458 (29·4) 584 (20·0) Eligibility for HPV vaccination 5 < 0·001 Catch-up 2,432 (54·2) 934 (59·9) 1,498 (51·2) Routine vaccination 2,056 (45·8) 626 (40·1) 1,430 (48·8) Partner 0·03 No steady partner 2,917 (65·6) 977 (63·3) 1,940 (66·9) Steady partner 1,395 (31·4) 523 (33·9) 872 (30·1) Open relationship 132 (3·0) 44 (2·8) 88 (3·0) History of hormonal contraceptive use < 0·001 No 169 (3·8) 90 (5·8) 79 (2·7) Yes 4,163 (92·8) 1,415 (90·6) 2,748 (93·9) Unknown/missing 156 (3·5) 56 (3·6) 100 (3·4) Sexual behaviour 0·32 WSM 4,157 (92·6) 1,437 (92·1) 2,720 (92·9) WSW 331 (7·4) 124 (7·9) 207 (7·1) Age sexual debut (years) 16 (15, 17) 16 (15, 17) 16 (15, 17) 0.02 Age sexual debut (years) 0·001 ≤ 14 580 (13·1) 240 (15·6) 340 (11·8) 15–16 2,099 (47·4) 719 (46·8) 1,380 (47·8) ≥ 17 1,745 (39·4) 578 (37·6) 1,167 (40·4) No. sex partners lifetime 7 (4, 11) 7 (4, 11) 7 (4, 11) 0·15 No. sex partners lifetime 0·13 0–4 1,241 (27·9) 458 (29·7) 783 (27·0) 5–9 1,610 (36·2) 536 (34·7) 1,074 (37·0) ≥ 10 1,592 (35·8) 549 (35·6) 1,043 (36·0) No. sex partners preceding 6 mos. 2 (1, 4) 2 (1, 3) 2 (1, 4) 0·01 No. sex partners preceding 6 mos. 0·02 0–1 1,189 (26·5) 451 (28·9) 738 (25·2) 2–3 2,939 (65·5) 996 (63·8) 1,943 (66·4) ≥ 4 359 (8·0) 113 (7·2) 246 (8·4) History of STI 0·06 No 2,238 (50·2) 741 (47·8) 1,497 (51·4) Yes 1,332 (29·9) 482 (31·1) 850 (29·2) Never tested 891 (20·0) 328 (21·1) 563 (19·3) Current Ct infection 6 0·92 Negative 3,682 (82·6) 1,283 (82·7) 2,399 (82·6) Positive 775 (17·4) 268 (17·3) 507 (17·4) Current Ng infection 6 0·98 Negative 4,367 (97·3) 1,518 (97·2) 2,849 (97·3) Positive 45 (1·0) 16 (1·0) 29 (1·0) Not tested 76 (1·7) 27 (1·7) 49 (1·7) HPV-16/18 7 299 (6·7) 256 (16·4) 43 (1·5) < 0·001 hrHPV 8 2,532 (56·4) 959 (61·4) 1,573 (53·7) < 0·001 Note: P-value based on a chi-squared test for categorical variables and Wilcoxon rank-sum test for continuous, due to their non normal distributed nature. Totals may vary due to missings. Migration background: 17 missings; education: 4 missings; partner 44 missings; age sexual debut 64 missings; no. sexual partners lifetime 45 missings; no. sexual partners preceding 6 months: 3 missings. Abbreviations: Ct Chlamydia trachomatis; Ng Neisseria gonorrhoeae; hrHPV high-risk HPV; HPV human papilloma virus; IQR interquartile range; SHC sexual health clinic; STI sexually transmitted infection; WSM women having sex with men only; WSW women having sex with women. 1: Multiple SHCs from the provinces Friesland, Groningen and Drenthe. 2: Multiple SHCs from the provinces Overijssel and Gelderland. 3: Multiple SHC from the provinces Noord-Brabant and Limburg. 4: (Pre)univerisity is defined as higher general secondary education, pre-university education, university for applied sciences and university. Other is defined as all other levels of education. 5: Eligibility is based on birth cohorts. Catch-up consisted of birth cohort 1993–1996, routine vaccination of birth cohort ≥ 1997. 6: Diagnosis at the same visit to the SHC at which the participant was included in this study. 7: DNA-positive for at least one of HPV-16/18. 8: DNA-positive for at least one of HPV-16/18/31/33/35/39/45/51/52/56/58/59. Table 2 Characteristics of the female study population of the PASSYON study who had been eligible for HPV vaccination in the Netherlands, by eligibility for catch-up or routine HPV vaccination based on birth cohort, the Netherlands, 2011–2021 Total Catch-up campaign Routine vaccination Variable n (%) or median (IQR) n (%) or median (IQR) n (%) or median (IQR) p-value Total 4,488 2,432 2,056 Study round < 0·001 2011 61 (1·4) 61 (2·5) 0 (0·0) 2013 325 (7·2) 325 (13·4) 0 (0·0) 2015 701 (15·6) 648 (26·6) 53 (2·6) 2017 1,122 (25·0) 850 (35·0) 272 (13·2) 2019 1,115 (24·8) 468 (19·2) 647 (31·5) 2021 1,164 (25·9) 80 (3·3) 1,084 (52·7) Location SHC < 0·001 Amsterdam 1,315 (29·3) 735 (30·2) 580 (28·2) Rotterdam 663 (14·8) 402 (16·5) 261 (12·7) Utrecht 469 (10·5) 252 (10·4) 217 (10·6) Northern Netherlands 1 425 (9·5) 221 (9·1) 204 (9·9) Middle Netherlands 2 534 (11·9) 236 (9·7) 298 (14·5) Southern Netherlands 3 1,082 (24·1) 586 (24·1) 496 (24·1) Age (years) 21 (19, 22) 21 (20, 23) 20 (19, 21) < 0·001 Age (years) < 0·001 16–18 655 (14·6) 272 (11·2) 383 (18·6) 19–21 2,373 (52·9) 1,146 (47·1) 1,227 (59·7) 22–24 1,460 (32·5) 1,014 (41·7) 446 (21·7) Migration background 0·19 None (Dutch) 3,522 (78·8) 1,900 (78·6) 1,622 (79·0) Migrant 257 (5·7) 128 (5·3) 129 (6·3) Child of migrant 692 (15·5) 390 (16·1) 302 (14·7) Education 4 0·56 (Pre)university 3,442 (76·8) 1,874 (77·1) 1,568 (76·3) Other 1,042 (23·2) 556 (22·9) 486 (23·7) Self-reported vaccination status < 0·001 Unvaccinated 1,560 (34·8) 934 (38·4) 626 (30·4) Vaccinated 2,928 (65·2) 1,498 (61·6) 1,430 (69·6) Partner < 0·001 No steady partner 2,917 (65·6) 1,588 (65·8) 1,329 (65·4) Steady partner 1,395 (31·4) 780 (32·3) 615 (30·3) Open relationship 132 (3·0) 45 (1·9) 87 (4·3) History of hormonal contraceptive use < 0·001 No 169 (3·8) 90 (5·8) 79 (2·7) Yes 4,163 (92·8) 1,415 (90·6) 2,748 (93·9) Unknown/missing 156 (3·5) 56 (3·6) 100 (3·4) Sexual behaviour < 0·001 WSM 4,157 (92·6) 2,283 (93·9) 1,874 (91·1) WSW 331 (7·4) 149 (6·1) 182 (8·9) Age sexual debut (years) 16 (15, 17) 16 (15, 17) 16 (15, 17) 0·01 Age sexual debut (years) 0·01 ≤ 14 1,745 (39·4) 902 (37·5) 843 (41·8) 15–16 581 (13·1) 329 (13·7) 252 (12·5) ≥ 17 2,098 (47·4) 1,175 (48·8) 923 (45·7) No. sex partners lifetime 7 (4, 12) 8 (4, 12) 6 (4, 11) < 0·001 No. sex partners lifetime < 0·001 0–4 1,241 (27·9) 612 (25·5) 629 (30·8) 5–9 1,610 (36·2) 858 (35·7) 752 (36·8) ≥ 10 1,592 (35·8) 932 (38·8) 660 (32·3) No. sex partners preceding 6 mos. 2 (1, 4) 2 (1, 4) 2 (1, 3) 0·11 No. sex partners preceding 6 mos. 0·28 0–1 1,189 (26·5) 623 (25·6) 566 (27·5) 2–3 2,937 (65·5) 1,603 (66·0) 1,334 (64·9) ≥ 4 359 (8·0) 203 (8·4) 156 (7·6) History of STI 0·46 No 2,239 (50·2) 1,216 (50·1) 1,023 (50·2) Yes 1,332 (29·9) 739 (30·5) 593 (29·1) Never tested 890 (20·0) 470 (19·4) 420 (20·6) Current Ct infection 5 < 0·001 Negative 3,682 (82·6) 2,052 (84·9) 1,630 (79·9) Positive 775 (17·4) 364 (15·1) 411 (20·1) Current Ng infection 5 < 0·001 Negative 4,367 (97·3) 2,348 (96·5) 2,019 (98·2) Positive 45 (1·0) 24 (1·0) 21 (1·0) Not tested 76 (1·7) 60 (2·5) 16 (0·8) HPV-16/18 6 299 (6·7) 205 (8·4) 94 (4·6) < 0·001 hrHPV 7 2,533 (56·4) 1,427 (58·7) 1,106 (53·8) 0·001 Note: Eligibility for HPV vaccination is based on birth cohorts. Catch-up consisted of birth cohort 1993–1996, routine vaccination of birth cohort ≥ 1997. P-value based on a chi-squared test for categorical variables and Wilcoxon rank-sum test for continuous, due to their non normal distributed nature. Totals may vary due to missings. Migration background: 17 missings; education: 4 missings; partner 44 missings; age sexual debut 64 missings; no. sexual partners lifetime 45 missings; no. sexual partners preceding 6 months: 3 missings. Abbreviations: Ct Chlamydia trachomatis; Ng Neisseria gonorrhoeae; hrHPV high-risk HPV; HPV human papilloma virus; IQR interquartile range; SHC sexual health clinic; STI sexually transmitted infection; WSM women having sex with men only; WSW women having sex with women. 1: Multiple SHCs from the provinces Friesland, Groningen and Drenthe. 2: Multiple SHCs from the provinces Overijssel and Gelderland. 3: Multiple SHC from the provinces Noord-Brabant and Limburg. 4: (Pre)university is defined as higher general secondary education, pre-university education, university for applied sciences and university. Other is defined as all other levels of education. 5: Diagnosis at the same visit to the SHC at which the participant was included in this study. 6: DNA-positive for at least one of HPV-16/18. 7: DNA-positive for at least one of HPV-16/18/31/33/35/39/45/51/52/56/58/59. Overall, 6.7% of the participants tested positive for HPV-16 and/or HPV-18 (n = 299) and 56.4% for at least one hrHPV genotype (n = 2,532) (Table 1 ). The type-specific and grouped HPV prevalences for the twelve hrHPV genotypes and the lrHPV genotypes 6/11 by vaccination status can be found in Fig. 1 . There were important differences between women who had been vaccinated and those who had not been vaccinated (Table 1 ). Compared to unvaccinated women, vaccinated women were more likely to have no migration background, to have done (pre)university education, to have an older age at sexual debut and to have no history of STI. Compared to women who had been eligible for routine vaccination, those who had been eligible for catch-up HPV vaccination were more likely to be of older age at inclusion, to be unvaccinated, to have an older age at sexual debut, and higher number of sexual partners lifetime and preceding 6 months (Table 2 ). VE estimates Unadjusted VE against at least one of the bivalent genotypes was 91.2% (95% confidence interval (CI): (87.9; 93.7). VE against HPV-16 was 92.7% (95%CI: (88.9; 95.4), and 88.5% (95%CI: (82.0; 93.0) against HPV-18. More details on other type-specific and grouped VE can be found in Supplementary table 2. The PS stratification adjusted VE against genital HPV-16 DNA-positivity was 93.5% (95%CI: 89.8; 95.9); for HPV-18 this was 89.5 (95%CI: 83.0; 93.6) (Fig. 2 ). Next to the vaccine targeted genotypes, statistically significant protection was found against HPV-31 (63.9%; 95%CI: 54.1; 71.6), HPV-33 (51.5%; 95%CI: 32.6; 65.0), HPV-35 (48.5%; 95%CI: 23.0; 65.5), HPV-45 (79.6%; 95%CI: 64.7; 88.2), HPV-52 (18.0%; 95%CI: 6.2; 28.4) and HPV-58 (31.4%; 95%CI: 8.7; 48.5) (Fig. 2 ). Significant negative VE was found against HPV-59: -42.6% (95%CI: -92.9; -5.4). The VE against grouped genital DNA-positivity of at least one of the bivalent genotypes was 92.1% (95%CI: 88.9; 94.3). Grouped VE against any hrHPV was 12.8% (95%CI: 7.9; 17.4). More grouped estimates can be found in Fig. 1 . Stratified VE estimates No statistically significant differences were found in VE estimates of the birth cohort that had been eligible for the catch-up campaign (birth cohort 1993–1996, eligible at age 13–16 years) and VE estimates of the birth cohort which had been eligible for routine HPV vaccination within the NIP (birth cohort ≥ 1997, eligible at age 12) (Fig. 3 A, Supplementary table 3). VE against genital HPV-16 was 92.1% (95%CI: 86.6; 95.4) for the birth cohort of the catch-up campaign, and 94.9% (95%CI: 87.8; 97.8) for the birth cohort of routine vaccination (p for interaction = 0.54). For HPV-18 this was 92.2% (95%CI: 84.1; 96.2) and 86.8 (95%CI: 74.0; 93.3) (p for interaction = 0.37). More details can be found in Fig. 3 A and Supplementary table 3. For women who had been eligible for catch-up vaccination, stratified analyses by age of sexual debut relative to the year they had been offered HPV vaccination, i.e. by having been potentially sexually active at time of vaccination eligibility (Fig. 3 B, Supplementary table 4). VE estimates were slightly lower for five of the seven VE estimates for women who were sexually active before or in the same year as being eligible for vaccination, although none of these differences were statistically significant. The VE against genital HPV-16 and/or HPV-18 was 94.5% (95%CI: 89.9; 97.0) for women who were not sexually active before having been eligible for vaccination, and 87.5% (95%CI: 76.1; 93.4) for those who were sexually active before or at the same age as being eligible for vaccination (p for interaction 0.07). In the VE analyses stratified by number of sex partners in the preceding 6 months, and by years sexually active, also no significant differences were observed in type-specific and grouped VE between the strata (Supplementary Fig. 1). Sensitivity analyses: In the sensitivity analyses, no differences were found in VE estimates between the two methods used for adjustment for differences in characteristic between vaccinated and unvaccinated women and differences in study population over the study rounds. Type-specific and grouped VE were comparable for unadjusted estimates, estimates adjustments with multivariable logistic regression, and estimates with PS stratification (Supplementary Fig. 2). 4002 women were included in the sensitivity analysis restricted to women who were offered a 3-dose vaccination schedule (all born in 1993–2000), and 331 were excluded as they were born in 2001 or later. No statistically significant differences were observed between VE of the catch-up cohort and the routine vaccination cohort (Supplementary Fig. 3). Discussion This study demonstrated a very high VE of the bivalent HPV vaccine against female genital HPV positivity for the targeted HPV genotypes HPV-16 and HPV-18 during the girls-only HPV vaccination period in the Netherlands. Significant cross-protection was found against 6 other hrHPV genotypes, being HPV-31, 33, 35, 45, 52 and 58. No significant differences were found in VE between women in our study who had been eligible for the 2009 catch-up campaign for girls aged 13–16 and women who had been eligible for routine vaccination at age 12 as part of the Dutch NIP. A strength of our study was the large study population, of whom 4,488 were included in the main analyses. This is substantially more than the preceding VE analysis based on PASSYON data of 1,087 women[ 11 ]. Additionally, data from multiple geographical locations were used, resulting in a high coverage and representativity for the country. Furthermore, the Dutch setting is uniquely suited to assess VE of the bivalent vaccine post-licencing, as the Netherlands is one of the few high-income countries that uses only the bivalent vaccine[ 27 ], and has done so since the start of HPV vaccination within the NIP. Lastly, the study population was aged 16–24 years old, the age span in which the incidence of female genital HPV infections is at its peak[ 28 ]. Some limitations should be mentioned. First, several variables were self-reported, such as sexual behaviour and vaccination status, possibly leading to recall or social desirability bias. However, sexual behaviour is hard to measure otherwise, and previous analyses from the PASSYON study showed that self-reported vaccination status of women correlated very well with high antibody levels[ 11 ]. Second, vaccination status was not reported, or genital swab not provided by 518 women, who were otherwise eligible for analyses. This might have led to selection bias. Based on variables such as age, age at sexual debut and number of sexual partners, there is no indication to expect this. Third, the study population consisted of SHC clients. As these women are likely more sexually active than their peers not visiting SHCs, this might limit the generalizability of the results. Nevertheless, stratified analyses showed that VE estimates were comparable across strata of sexual behaviour, which favours generalizability. Fourth, to minimise confounding caused by differences in study populations between study rounds and vaccination status of women, we used PS stratification to adjust. Nevertheless, this only adjusts for measured variables. We had no information on type of sexual practices and smoking behaviour, so we were not able to adjust for these variables. Finally, we were unable to conduct a comparison of VE of administering two doses vs. three doses. Due the pseudonymized study design, we could not link our data to a national vaccination database. Considering evidence suggesting that a single dose provides comparable efficacy to three doses of bivalent HPV vaccination against HPV infection[ 29 – 31 ], we would not expect large differences in VE between different doses groups. We therefore defined being vaccinated as 'having received at least one dose'. The VE estimates of type-specific and grouped VE against genital HPV-16 and/or HPV-18 of this study are in agreement with previous literature; the estimates are in line with previous vaccine efficacy trials of the bivalent HPV vaccine[ 4 , 32 ], and with post-licensing observational studies among young women[ 6 , 8 , 10 ]. Some of these studies assessed persistent infection instead of HPV positivity, but reported comparable VE estimates against female genital HPV. We found significant cross-protection against 6 genotypes, being HPV-31, 33, 35, 45, 52 and 58. These genotypes are associated with an additional 18% of cervical cancers worldwide[ 3 ]. Cross-protection against these genotypes had been observed before in HPV vaccine studies, although never before all these 6 genotypes within one study. The PATRICIA trial, the largest phase III trial, observed significant cross-protection against persistent infection with HPV-31, 33, 45 and 52 with comparable estimates, and against incident infection with HPV-35[ 33 , 34 ]. Another large clinical trial, the Costa Rica HPV vaccine Trial, assessed cross-protection of the bivalent HPV vaccine against incident infection[ 35 ]. They observed not only cross-protection against previously mentioned genotypes (HPV-31/33/35/45), but also against HPV-58 of 21.2% (95%CI: 4.2; 35.3), somewhat lower than our estimate. In a systematic review on cross-protective effects of the bivalent HPV vaccine, outcomes of 17 observational studies were compared[ 5 ], either as VE or prevalence over time. Of these studies, being from Japan, Luxembourg, Scotland, Finland and the Netherlands, 11 observed cross-protection: nine against HPV-31, eight against HPV-45, five against HPV-31, and two against HPV-52[ 5 ]. Finally, a previous analysis of the PASSYON study[ 11 ] did not observe the significant cross-protection against HPV-33 and HPV-58 observed in our current analysis study, which is probably explained by the greater power of the current analyses due to the larger study population. A statistically significant negative VE for HPV-59 was observed. The SPF 10 -DEIA-LiPA 25 is known to detect HPV-59 less well in the presence with co-infection of other hrHPV genotypes[ 36 ]. Effective vaccination leads to a decrease in co-infections with other genotypes, making it more likely for HPV-59 to be detected in vaccinated compared to unvaccinated women[ 36 ]. This might lead to a biased VE estimate as shown previously[ 36 ]. In this study, VE estimates were similar for women who had been eligible for the catch-up campaign in 2009 at the age 13–16 years and for women who had been eligible from 2010 onwards for routine HPV vaccination at 12 years as part of the Dutch NIP. Even for women whom were potentially sexually active at the time they had been offered HPV vaccination, the VE was very high. Only one other study, also conducted in the Netherlands, compared routine vaccination to the catch-up, but did not report VE estimates[ 37 ]. That study did not find different hrHPV positivity rates for women vaccinated in the catch-up campaign compared to those vaccinated in routine vaccination, in line with findings of the current study[ 37 ]. Our results are strongly suggestive that catch-up campaigns up to the age of 16 is probably as effective, in terms of VE, as routine vaccination at an earlier age. This is in line with other studies that found that vaccination up to age 16 years was associated with reduced risk of cervical cancer protection; protection was much lower for females vaccinated at the age of 17 years and above[ 38 , 39 ]. Therefore it seems that catch-up campaigns up to the age of 16 years might be most effective in terms of protection. Conclusions In our study a high VE of bivalent HPV vaccination was demonstrated against genital HPV-16 and HPV-18 DNA-positivity for young women in the Netherlands. Additionally, significant cross-protection was found for six other hrHPV genotypes. Together, these eight genotypes are responsible for 89% of cervical cancers worldwide. These findings should be used in cost-effectiveness studies when deciding about the choice of vaccine in NIPs. Moreover, this study demonstrated that catch-up campaigns focussed on girls up to age 16 years is likely to be as protective as routine vaccination at an earlier age. List Of Abbreviations CI Confidence interval hrHPV high–risk HPV HPV Human papillomavirus IPW Inverse probability weighting IQR Interquartile range lrHPV low–risk HPV NIP National immunisation programme PS propensity score RR Relative risk SHC Sexual health clinic STI Sexually transmitted infection VE Vaccine effectiveness Declarations The PASSYON study group Helmie van der Meijden, Karlijn Kampman, Elske Hoornenborg, Annet Bak, Marga Smit, Harriette van Buel, Ferna Neienhuijsen, Marlot Ippel, Dianne Schriemer, Inez Swart, and Denise Twisk. Acknowledgements The authors would like to thank the following for their valuable contributions to the design or execution of the study: Hein Boot (deceased), Elske van Logchem, Naomi van Marm, Suzan Leussink, Tim Severs, Rutger Schepp, Kahren van Eer, Thomas Langenburg, Najima Lamkaraf, Maarten Schipper, Petra Woestenberg, Rianne Vriend and Marianne van der Sande. Furthermore, the centres for sexual health, including all nurses and physicians, within the Public Health Services and the hospitals are acknowledged for their permission to collect data from their clients and for their efforts. The authors acknowledge the medical microbiologic laboratories and their staff for storage and testing of the samples. Ethics approval and consent to participate This study was approved by Medical Ethics Committee of the University of Utrecht, The Netherlands (reference number: 08/397). Participants gave informed consent to participate in the study before taking part. Consent for publication Not applicable Availability of data and materials This study collected data which has been pseudonymised. Pseudonymised individual participant data can be requested for scientific use with a methodologically sound proposal. In case of data sharing, receivers of data will need to sign a data transfer agreement. Competing interests The institution of M.F. Schim van der Loeff and J.C.M Heijne received study funding for an investigator-initiated study from GSK. M.F. Schim van der Loeff served on advisory boards of MSD and Novosanis. All other authors report no conflict of interest. Funding This work was supported by the Ministry of Health, Welfare and Sport, the Netherlands. The funders had no role in study design, data collection and analysis, interpretation of data, decision to publish, or preparation of the manuscript. Author’s contributions BH van Benthem was the principal investigator of the PASSYON study, and together with HE de Melker responsible for funding acquisition. AJ King was responsible for supervising the genital sample analyses and the interpretation of the HPV DNA-sample analyses. JMA Kusters, AJ King and BH van Benthem were responsible for validation and verification of the data. JMA Kusters, MF Schim van der Loeff, JCM Heijne and BHB van Benthem were responsible for the conception, methodology and design of the current study. JMA Kusters was responsible for conducting the formal analyses. All authors participated in the interpretation of the results. The original manuscript draft, including figures and tables, was created by JMA Kusters, and all authors contributed to editing of the manuscript and approving the final draft. Finally, BH van Benthem, JCM Heijne and MF Schim van der Loeff were responsible for supervising JMA Kusters. References de Sanjose S, Brotons M, Pavon MA. 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Supplementary Files VEJMAKustersSupplementsBMC.docx Cite Share Download PDF Status: Published Journal Publication published 15 Oct, 2024 Read the published version in BMC Medicine → Version 1 posted Editorial decision: Revision requested 11 Jul, 2024 Reviews received at journal 19 Jun, 2024 Reviews received at journal 19 Jun, 2024 Reviewers agreed at journal 10 Jun, 2024 Reviewers agreed at journal 10 Jun, 2024 Reviewers agreed at journal 22 May, 2024 Reviewers invited by journal 07 May, 2024 Editor assigned by journal 29 Apr, 2024 Submission checks completed at journal 29 Apr, 2024 First submitted to journal 26 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4330011","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":325631115,"identity":"3663ecec-5f3e-4f9f-a05d-f737cf92dcb4","order_by":0,"name":"Johannes MA Kusters","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIie3OMQrCMBiG4YTA71KdWzp4hYSCIBTPIhS6iOjoGBHiYp3r5BV0c6wUdFGzFlwUwd1RqKBWRRwaHR3yLh9JeCAI6XR/GOaPpc+ziyDb9k+E3Nd/EpoH3r1I/D7nRfrBfneaIYdKOT90UtkqmY06aSsIHiwdNlqhCk08wtZiWxVmc0JCFQl9sIsCuTQhYHX5loKxnhBDRcZHsC93IuPCmaebH0gIYGNx+1jkAeYQUSgEX8jAJywQpmMlnmN1hZeRWEVYf4F3Z+GyoZzvTzyt0XKvOD0YHQXh2Zift1E+QKisetTpdDpd1hXwRUf6+beNDwAAAABJRU5ErkJggg==","orcid":"","institution":"National Institute for Public Health and the Environment (RIVM)","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Johannes","middleName":"MA","lastName":"Kusters","suffix":""},{"id":325631116,"identity":"da848711-95ee-4305-b0ed-c1d9e28dba98","order_by":1,"name":"Maarten F Schim Loeff","email":"","orcid":"","institution":"Amsterdam UMC","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maarten","middleName":"F Schim","lastName":"Loeff","suffix":""},{"id":325631117,"identity":"9337b925-44ef-4ba7-ad19-5e3ebf06bfdc","order_by":2,"name":"Birgit HB Benthem","email":"","orcid":"","institution":"National Institute for Public Health and the Environment (RIVM)","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Birgit","middleName":"HB","lastName":"Benthem","suffix":""},{"id":325631118,"identity":"586d0d3a-dcbb-4fb3-a032-c8ea0e3d8bb1","order_by":3,"name":"Audrey J King","email":"","orcid":"","institution":"National Institute for Public Health and the Environment (RIVM)","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Audrey","middleName":"J","lastName":"King","suffix":""},{"id":325631119,"identity":"79ddf435-7010-4a25-9e13-17f469ec3bf4","order_by":4,"name":"Hester E Melker","email":"","orcid":"","institution":"National Institute for Public Health and the Environment (RIVM)","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hester","middleName":"E","lastName":"Melker","suffix":""},{"id":325631120,"identity":"5ad7531e-accd-49ed-a4f1-ab212632db8e","order_by":5,"name":"Titia Heijman","email":"","orcid":"","institution":"Public Health Service of Amsterdam","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Titia","middleName":"","lastName":"Heijman","suffix":""},{"id":325631121,"identity":"bd6fa2ad-da29-4082-98c2-bd7726906489","order_by":6,"name":"Janneke CM Heijne","email":"","orcid":"","institution":"Public Health Service of Amsterdam","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Janneke","middleName":"CM","lastName":"Heijne","suffix":""}],"badges":[],"createdAt":"2024-04-26 13:53:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4330011/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4330011/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12916-024-03686-4","type":"published","date":"2024-10-15T15:57:31+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":60707330,"identity":"f423d8b3-1d14-4202-ad86-72b1a0921bfc","added_by":"auto","created_at":"2024-07-19 19:32:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":853355,"visible":true,"origin":"","legend":"\u003cp\u003eType-specific and grouped prevalences and 95% confidence intervals of genital HPV DNA-positivity among female participants who had been eligible for HPV vaccination in the Netherlands from the PASSYON study (2011-2021), by vaccination status\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFootnote: 2vHPV is DNA-positive for at least one of HPV-16/18; crosstypes 1 is DNA-positive for at least one of HPV-31/33/45; crosstypes 2 is DNA-positive for at least one of HPV-31/33/35/45/52/58; 9vhrHPV is DNA positive for at least one of HPV-16/18/31/33/45/52/58; \u0026nbsp;hrHPV is DNA-positive for at least one of \u003c/em\u003e16/18/31/33/35/39/45/51/52/56/58/59\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations: 2vHPV bivalent HPV; 9vhrHPV nonavalent high-risk HPV; HPV human papillomavirus; hrHPV high-risk HPV.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"VEFigure1prevalencebyvaccinationBMC.png","url":"https://assets-eu.researchsquare.com/files/rs-4330011/v1/1820b3ffeff217ac0944fffb.png"},{"id":60707332,"identity":"105719be-a90b-4d91-b504-f0227eaed628","added_by":"auto","created_at":"2024-07-19 19:32:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":832146,"visible":true,"origin":"","legend":"\u003cp\u003eType-specific and grouped vaccine effectiveness of the bivalent HPV vaccine against genital HPV DNA-positivity for female participants who had been eligible for HPV vaccination included in the PASSYON study, the Netherlands, 2011-2021.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFootnote: 2vHPV is DNA-positive for at least one of HPV-16/18; crosstypes 1 is DNA-positive for at least one of HPV-31/33/45; crosstypes 2 is DNA-positive for at least one of HPV-31/33/35/45/52/58; 9vhrHPV is DNA positive for at least one of HPV-16/18/31/33/45/52/58; hrHPV is DNA-positive for at least one of \u003c/em\u003e16/18/31/33/35/39/45/51/52/56/58/59\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations: 2vHPV bivalent HPV; 9vhrHPV nonavalent high-risk HPV; CI confidence interval; HPV human papillomavirus; hrHPV high-risk HPV; VE vaccine effectiveness.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"VEFigure2VEestimationsnostratBMC.png","url":"https://assets-eu.researchsquare.com/files/rs-4330011/v1/b71251cbf528b5202e8dcf6e.png"},{"id":60707333,"identity":"7e286cb9-756b-4c5b-802d-e93a9c5df796","added_by":"auto","created_at":"2024-07-19 19:32:32","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":693075,"visible":true,"origin":"","legend":"\u003cp\u003eStratified analyses of type-specific and grouped vaccine effectiveness of the bivalent HPV vaccine against genital HPV DNA-positivity for female participants who had been eligible for HPV vaccination within the catch-up campaign and routine vaccination included in the PASSYON study, the Netherlands, 2011-2021.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFootnote: Panel A presents stratified VE analyses by birth cohort, where birth cohort 1993-1996 had been eligible for the catch-up campaign and birth cohort ≥1997 for routine vaccination. Panel B presents stratified analyses by having been sexually active before or at the same age as having been eligibility for HPV vaccination for women of the catch-up cohort.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e2vHPV is DNA-positive for at least one of HPV-16/18; crosstypes 1 is DNA-positive for at least one of HPV-31/33/45; crosstypes 2 is DNA-positive for at least one of HPV-31/33/35/45/52/58; 9vhrHPV is DNA positive for at least one of HPV-16/18/31/33/45/52/58; hrHPV is DNA-positive for at least one of \u003c/em\u003e16/18/31/33/35/39/45/51/52/56/58/59\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations: 2vHPV bivalent HPV; 9vhrHPV nonavalent high-risk HPV; HPV human papillomavirus; hrHPV high-risk HPV; VE vaccine effectiveness.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"VEFigure3VEestimationsstratifiedanalysesBMC.png","url":"https://assets-eu.researchsquare.com/files/rs-4330011/v1/ce9b26877879b9632e343082.png"},{"id":67148976,"identity":"22507916-2075-498d-93f3-def0298542f0","added_by":"auto","created_at":"2024-10-21 16:10:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3775878,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4330011/v1/a0cec362-c089-4554-a864-6db37ad725be.pdf"},{"id":60707331,"identity":"176f93f1-3a40-49d3-8727-ef61c17d7ba5","added_by":"auto","created_at":"2024-07-19 19:32:32","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":246340,"visible":true,"origin":"","legend":"","description":"","filename":"VEJMAKustersSupplementsBMC.docx","url":"https://assets-eu.researchsquare.com/files/rs-4330011/v1/88b267f18a5b5c9000562123.docx"}],"financialInterests":"Competing interest reported. The institution of M.F. Schim van der Loeff and J.C.M Heijne received study funding for an investigator-initiated study from GSK. M.F. Schim van der Loeff served on advisory boards of MSD and Novosanis. All other authors report no conflict of interest.","formattedTitle":"Vaccine Effectiveness Of Bivalent HPV Vaccination Against Genital HPV Of A Catch-Up Campaign And 12 Years Routine Vaccination For Girls-Only: A Biennial Repeated Cross-Sectional Study","fulltext":[{"header":"Background","content":"\u003cp\u003ePersistent human papillomavirus (HPV) infections could lead to anogenital warts (AGWs) or cancer[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Approximately 5% of new cancer cases worldwide are attributable to HPV, approximately 3-3.5% by genotype HPV-16 alone[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Several prophylactic vaccines are proven to be effective against persistent HPV infections and CIN2\u0026thinsp;+\u0026thinsp;and are available across the world. All protect against the two most oncogenic genotypes (HPV-16/18), responsible for about 71% of cervical cancers[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], and some vaccines offer additional protection to two low-risk HPV (lrHPV) genotypes, and to five additional high-risk HPV (hrHPV) genotypes. The bivalent vaccine Cervarix\u0026reg; is targeted against HPV-16 and HPV-18[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and has shown cross-protection effectiveness against other hrHPV genotypes[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePost-licencing observational vaccine effectiveness (VE) studies are important after introduction of a vaccine, to understand the effectiveness in real-world settings. Up to date, several observational studies have been conducted to assess the VE for the bivalent vaccine[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, some of those studies did not assess VE type-specifically[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], or were from countries that offered more than one vaccine type at the same time[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Herd-immunity provided by another HPV vaccine may influence observed VE of the bivalent vaccine. Other observational studies (including from our own group) used mostly data of women vaccinated within a catch-up campaign[\u003cspan additionalcitationids=\"CR11 CR12 CR13\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In catch-up campaigns it is more likely that some girls have become sexually active before receiving a vaccine than in routine vaccination; therefore VE estimates based on catch-up data might not represent VE in routine vaccination settings. Studies comparing catch-up campaign VE with routine vaccination VE are scarce, and are mostly modelling studies rather than observational studies[\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. As more countries start HPV vaccination or start gender-neutral vaccination, mostly introduced in combination with catch-up campaigns, this comparison could inform catch-up strategies. Real-world comparisons of effectiveness between catch-up campaigns and routine vaccination are hence needed.\u003c/p\u003e \u003cp\u003eSince the introduction of HPV vaccination in the National Immunisation Programme (NIP) of the Netherlands, the bivalent HPV vaccine has exclusively been used. This started with a catch-up campaign in 2009 targeting girls born in 1993\u0026ndash;1996[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], and became part of routine vaccination in 2010, starting with birth cohort 1997. The Netherlands is one of the few countries which started with bivalent HPV vaccination, and has continued doing so for girls-only until 2022. This makes the Dutch setting unique, and suitable for assessing VE of the bivalent vaccine in real-world post-licencing settings. It additionally provides an opportunity to compare VE of the bivalent HPV vaccine between birth cohorts vaccinated in the catch-up campaign and those vaccinated in the routine vaccination programme.\u003c/p\u003e \u003cp\u003eIn this study we aimed to (1) assess the type-specific and grouped VE of the bivalent HPV vaccine against female genital HPV DNA-positivity during the 12 year girls-only vaccination period. Additionally, (2) we aimed to compare VE between women offered vaccination during the catch-up campaign to those offered vaccination during routine HPV vaccination.\u003c/p\u003e"},{"header":"Methods and materials","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy setting\u003c/h2\u003e \u003cp\u003eThe PApillomavirus Surveillance among Sti clinic YOungsters in the Netherlands (PASSYON) study is a biennial repeated cross-sectional study among young adult sexual health clinic (SHC) clients[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. During each study round, for approximately 2 months SHC clients from 10\u0026ndash;14 SHCs aged 16\u0026ndash;24 years were asked to participate. After signing a written consent, participants were asked to self-collect a genital swab sample for HPV testing. Women were instructed to collect the cervicovaginal swab sample, by inserting a swab (Copan Diagnostics, Italy) about 4 cm into the vagina, until resistance was felt, and to turn the swab around along the walls of the vagina for about 15 seconds. All swabs were placed in a tube with 1 ml universal transport medium (Copan Diagnostics, Italy) immediately after the swab was taken.\u003c/p\u003e \u003cp\u003eAdditionally, participants were asked to complete a written questionnaire on demographics and sexual behaviour (such as number of sexual partners lifetime and in preceding 6 months, age of sexual debut, and history of STI). Participants also reported whether they had been vaccinated against HPV. Finally, diagnoses from routine STI testing were available for analyses.\u003c/p\u003e \u003cp\u003eFor the current analyses, data from the second through seventh study round of PASSYON (2011-21) were used, as these study rounds cover the era in which only girls were invited for HPV vaccination. Only women who had been eligible for HPV vaccination were included, based on their year of birth. Having been eligible for HPV vaccination was defined as being born in 1993 or later, as this was the first birth cohort which had been invited for the catch-up vaccination. Other inclusion criteria were provision of a genital swab and having reported HPV vaccination status in the questionnaire.\u003c/p\u003e \u003cp\u003e This study was approved by Medical Ethics Committee of the University of Utrecht, The Netherlands (reference number: 08/397).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eLaboratory methods\u003c/h2\u003e \u003cp\u003eAll cervicovaginal swabs were stored at -20\u0026deg;C until processing. Samples were analysed within 12 months of collection, to ensure the quality of the sample. After thawing and vortexing, 200 \u0026micro;l of the material was used for DNA extraction using the MagnaPure platform (Total Nucleic Acid Isolation Kit, Roche, the Netherlands). Total DNA was eluted in 100 \u0026micro;l elution buffer and 10 \u0026micro;l was used to amplify HPV-DNA with the SPF\u003csub\u003e10\u003c/sub\u003e primer set. HPV-specific amplicons were detected using enzyme-linked immunoassay (HPV-DEIA, DDL Diagnostic Laboratory, the Netherlands). Positive samples were subsequently genotyped with the Line probe assay (HPV-LiPA, DDL Diagnostic Laboratory, the Netherlands), which is able to identify 25 genotypes (6, 11, 16, 18, 31, 33\u0026ndash;35, 39, 40, 42\u0026ndash;45, 51\u0026ndash;54, 56, 58, 59, 66, 68, 70, 74).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003eThe current report is an updated and elaborated follow-up of previous VE reports with data of the PASSYON study[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFirst, study population characteristics were described and compared by vaccination status. Type-specific and grouped genital HPV DNA-positivity prevalence was calculated for unvaccinated and vaccinated (\u0026ge;\u0026thinsp;1 dose) women, separately. Characteristics were also compared between women of birth cohort 1993-6 (these women had been eligible for catch-up vaccination) and women of birth cohort 1997 and later (these women had been eligible for routine vaccination). Finally, characteristics were compared between women who were excluded from the analyses because of missing genital sample or vaccination status, and those included in the analyses.\u003c/p\u003e \u003cp\u003eType-specific and grouped VE estimates were calculated using the relative risk (RR) for genital HPV DNA-positivity comparing vaccinated and unvaccinated women. VE was calculated as 1 minus the RR times 100%. First, unadjusted, crude VE estimates were calculated. Next, VE was calculated based on propensity score (PS) adjusted (see further) RRs. Type-specific estimates were made for the high-risk genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59, and for the low-risk genotypes 6 and 11. We also assessed prevalences of five different HPV groupings, defined as being DNA-positive for at least one of (1) the bivalent vaccine genotypes (HPV-16/18), (2) the cross-protected genotypes as observed previously[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] and widely reported in other studies (HPV-31/33/45), (3) the cross-protected types found in the current analysis, (4) the hrHPV genotypes covered by the nonavalent vaccine (HPV-16/18/31/33/45/52/58), and finally (5) all hrHPV genotypes (HPV- 16/18/31/33/35/39/45/51/52/56/58/59). These groupings were also used for other estimates in this study\u003c/p\u003e \u003cp\u003eTo adjust for differences in study population characteristics over the study rounds, and differences between unvaccinated and vaccinated women, PS stratification (also called subclassification) was used[\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. PS was calculated as the propensity of having been vaccinated based on study round, geographical location of the SHC, demographics (age, migration background and education), sexual behaviour (currently having a steady partner, history of hormonal anticonception use, number of sexual partners lifetime and in preceding 6 months) and having a history of other STIs. For each VE calculation, strata were created of the total study population based on quintiles of the PS distribution. Having defined strata, we assessed balance in co-variates in each stratum between the vaccinated and unvaccinated groups. If for each covariate the standardised mean difference between vaccinated and unvaccinated was smaller than 0.10, the balance was considered adequate. If this was not reached, a smaller number of strata was used. Within each stratum the RR risk was established using generalised linear regression models with binomial distribution and log link function[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In these models, HPV DNA-positivity was the dependent variable and self-reported vaccination status the independent variable. The overall effect was obtained by pooling the stratum-specific RR\u0026rsquo;s using stratum specific weights, which are based on the total number of included participants in that stratum.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStratified analyses\u003c/h2\u003e \u003cp\u003eFour stratified VE analyses were conducted. Stratified analyses were conducted by (1) birth cohort, where we distinguished women who had been eligible for the catch-up campaign (birth cohort 1993\u0026ndash;1996, 13\u0026ndash;16 years old at eligibility) from women who had been eligible for routine vaccination in the NIP (birth cohort\u0026thinsp;\u0026ge;\u0026thinsp;1997, 12 years old at eligibility).\u003c/p\u003e \u003cp\u003eFor women who had been eligible for the catch-up campaign, an additional stratified analysis was conducted: (2) we compared the VE for women who were, to women who were not, sexually active before, or at the same age the vaccine was offered, indicating being potentially sexually active around the time of vaccination. This was based on self-reported age at sexual debut and the age women had been eligible for vaccination based on their year of birth.\u003c/p\u003e \u003cp\u003eFor assessing generalisability of the VE estimates, VE analyses were conducted (3) stratified by number of sexual partners in the preceding 6 months (two categories, based on median), and (4) by years sexually active (age at inclusion minus age at sexual debut; three categories, based on tertiles). This was done as our study population might have been more sexually active than the general population.\u003c/p\u003e \u003cp\u003eTo test whether VE across the assessed strata differed, an interaction term between the stratifying variable and vaccination variable was added to the main VE model, to test for effect modification. All stratified analyses were done type-specifically for HPV-16 and HPV-18, and for all HPV-groupings as mentioned above. For each stratum, propensity scores were calculated and PS stratification was executed for that specific stratum.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSensitivity analyses\u003c/h3\u003e\n\u003cp\u003eTwo sensitivity analyses were conducted. First, First, instead of adjusting for confounding using PS stratification, we adjusted VE estimated with multivariable logistic regression, adjusting for variables associated with vaccination (being study round, age, education, migration background, age at sexual debut, history of STI).\u003c/p\u003e \u003cp\u003eAll women offered vaccination during the catch-up campaign (birth cohort 1993-6) were offered a three-dose schedule (0, 1 and 6 months). All women of birth cohort 1997\u0026ndash;2000 were offered HPV vaccination at age 12 years, in the same three-dose schedule. Women of birth cohort 2001 and later were offered vaccination in a two-dose schedule (0 and 6 months)[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In order to eliminate any potential differences in VE due to different dosing schedules, we performed a sensitivity analysis restricted to women who had been eligible for 3 doses.\u003c/p\u003e \u003cp\u003eAll analyses were performed using R RStudio (Version 1.3.959) with help of the cobalt and survey packages. For all analyses, statistical significance was defined as p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eIn the PASSYON study a total 13,535 adolescents participated, of whom 9,099 were female. Of those, 5,006 women had been eligible for vaccination. As 518 women had not indicated their vaccination status and/or did not provide a genital swab (422 women without reporting vaccination status, 96 without genital swab, eight missed both), these women were excluded (Supplementary table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Therefore, 4,488 women were eligible for the current analysis.\u003c/p\u003e \u003cp\u003eThe majority participated in the three study rounds 2017, 2019 and 2021 (75.7%). 34.8% reported to be unvaccinated (n\u0026thinsp;=\u0026thinsp;1,561) and 65.2% to be vaccinated (n\u0026thinsp;=\u0026thinsp;2,927) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Eligible for the catch-up campaign (birth cohort 1993\u0026ndash;1996) in our study population had been 2,345 women (54.2%) and eligible for routine HPV vaccination within the NIP (birth cohort\u0026thinsp;\u0026ge;\u0026thinsp;1997) had been 1,988 women (45.8%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The median number of sex partners in the preceding 6 months was 2 (IQR 1\u0026ndash;4), 29.9% had a history of an STI (n\u0026thinsp;=\u0026thinsp;1,332), and 17.4% had a current \u003cem\u003eChlamydia trachomatis\u003c/em\u003e infection (n\u0026thinsp;=\u0026thinsp;775). More information on study population characteristics can be found in Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of the female study population of the PASSYON study who had been eligible for HPV vaccination in the Netherlands, by self-reported vaccination status, the Netherlands, 2011\u0026ndash;2021\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnvaccinated\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVaccinated\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%) or median (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en (%) or median (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003en (%) or median (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,488\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,561\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,927\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStudy round\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2011\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (1\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (2\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (0\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2013\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e325 (7\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e139 (8\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e186 (6\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2015\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e701 (15\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e264 (16\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e437 (14\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2017\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,122 (25\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e404 (25\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e718 (24\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2019\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,115 (24\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e368 (23\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e747 (25\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2021\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,164 (25\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e351 (22\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e813 (27\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLocation SHC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAmsterdam\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,315 (29\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e456 (29\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e859 (29\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRotterdam\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e663 (14\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e231 (14\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e432 (14\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eUtrecht\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e469 (10\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e148 (9\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e321 (11\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNorthern Netherlands\u003c/em\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e426 (9\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e157 (10\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e269 (9\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMiddle Netherlands\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e534 (11\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e209 (13\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e325 (11\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSouthern Netherlands\u003c/em\u003e\u003csup\u003e\u003cem\u003e3\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,081 (24\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e360 (23\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e721 (24\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (19, 22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (19, 22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (19, 22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e16\u0026ndash;18\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e655 (14\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e224 (14\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e431 (14\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e19\u0026ndash;21\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,375 (52\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e822 (52\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,553 (53\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e22\u0026ndash;24\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,458 (32\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e515 (33\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e943 (32\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMigration background\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNone (Dutch)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,522 (78\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,148 (73\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,374 (81\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMigrant\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e257 (5\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e112 (7\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e145 (5\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eChild of migrant\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e692 (15\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e294 (18\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e398 (13\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEducation\u003c/b\u003e\u003csup\u003e\u003cb\u003e4\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e(Pre)university\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,442 (76\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,102 (70\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,340 (80\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eOther\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,042 (23\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e458 (29\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e584 (20\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEligibility for HPV vaccination\u003c/b\u003e\u003csup\u003e\u003cb\u003e5\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eCatch-up\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,432 (54\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e934 (59\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,498 (51\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRoutine vaccination\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,056 (45\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e626 (40\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,430 (48\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePartner\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNo steady partner\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,917 (65\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e977 (63\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,940 (66\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSteady partner\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,395 (31\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e523 (33\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e872 (30\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eOpen relationship\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e132 (3\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 (2\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e88 (3\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of hormonal contraceptive use\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNo\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e169 (3\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90 (5\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79 (2\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eYes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,163 (92\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,415 (90\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,748 (93\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eUnknown/missing\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e156 (3\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (3\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100 (3\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSexual behaviour\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eWSM\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,157 (92\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,437 (92\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,720 (92\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eWSW\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e331 (7\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e124 (7\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e207 (7\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge sexual debut (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (15, 17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (15, 17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (15, 17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge sexual debut (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e\u0026le;\u0026thinsp;14\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e580 (13\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e240 (15\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e340 (11\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e15\u0026ndash;16\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,099 (47\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e719 (46\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,380 (47\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e\u0026ge;\u0026thinsp;17\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,745 (39\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e578 (37\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,167 (40\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo. sex partners lifetime\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (4, 11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (4, 11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (4, 11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo. sex partners lifetime\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e0\u0026ndash;4\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,241 (27\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e458 (29\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e783 (27\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e5\u0026ndash;9\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,610 (36\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e536 (34\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,074 (37\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e\u0026ge;\u0026thinsp;10\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,592 (35\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e549 (35\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,043 (36\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo. sex partners preceding 6 mos.\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1, 4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1, 3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1, 4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo. sex partners preceding 6 mos.\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e0\u0026ndash;1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,189 (26\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e451 (28\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e738 (25\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2\u0026ndash;3\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,939 (65\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e996 (63\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,943 (66\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e\u0026ge;\u0026thinsp;4\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e359 (8\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e113 (7\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e246 (8\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of STI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNo\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,238 (50\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e741 (47\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,497 (51\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eYes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,332 (29\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e482 (31\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e850 (29\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNever tested\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e891 (20\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e328 (21\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e563 (19\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrent Ct infection\u003c/b\u003e\u003csup\u003e\u003cb\u003e6\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNegative\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,682 (82\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,283 (82\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,399 (82\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePositive\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e775 (17\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e268 (17\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e507 (17\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrent Ng infection\u003c/b\u003e\u003csup\u003e\u003cb\u003e6\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNegative\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,367 (97\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,518 (97\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,849 (97\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePositive\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (1\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (1\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (1\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNot tested\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 (1\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (1\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49 (1\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHPV-16/18\u003c/b\u003e\u003csup\u003e\u003cb\u003e7\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e299 (6\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e256 (16\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43 (1\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ehrHPV\u003c/b\u003e\u003csup\u003e\u003cb\u003e8\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,532 (56\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e959 (61\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,573 (53\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNote: P-value based on a chi-squared test for categorical variables and Wilcoxon rank-sum test for continuous, due to their non normal distributed nature. Totals may vary due to missings. Migration background: 17 missings; education: 4 missings; partner 44 missings; age sexual debut 64 missings; no. sexual partners lifetime 45 missings; no. sexual partners preceding 6 months: 3 missings.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAbbreviations: Ct Chlamydia trachomatis; Ng Neisseria gonorrhoeae; hrHPV high-risk HPV; HPV human papilloma virus; IQR interquartile range; SHC sexual health clinic; STI sexually transmitted infection; WSM women having sex with men only; WSW women having sex with women.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e1: Multiple SHCs from the provinces Friesland, Groningen and Drenthe.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2: Multiple SHCs from the provinces Overijssel and Gelderland.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e3: Multiple SHC from the provinces Noord-Brabant and Limburg.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e4: (Pre)univerisity is defined as higher general secondary education, pre-university education, university for applied sciences and university. Other is defined as all other levels of education.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e5: Eligibility is based on birth cohorts. Catch-up consisted of birth cohort 1993\u0026ndash;1996, routine vaccination of birth cohort\u003c/em\u003e\u0026thinsp;\u0026ge;\u0026thinsp;\u003cem\u003e1997.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e6: Diagnosis at the same visit to the SHC at which the participant was included in this study.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e7: DNA-positive for at least one of HPV-16/18.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e8: DNA-positive for at least one of HPV-16/18/31/33/35/39/45/51/52/56/58/59.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of the female study population of the PASSYON study who had been eligible for HPV vaccination in the Netherlands, by eligibility for catch-up or routine HPV vaccination based on birth cohort, the Netherlands, 2011\u0026ndash;2021\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCatch-up campaign\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRoutine vaccination\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%) or median (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003en (%) or median (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003en (%) or median (IQR)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,488\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,432\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,056\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStudy round\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2011\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61 (1\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 (2\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2013\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e325 (7\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e325 (13\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2015\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e701 (15\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e648 (26\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53 (2\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2017\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,122 (25\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e850 (35\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e272 (13\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2019\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,115 (24\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e468 (19\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e647 (31\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2021\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,164 (25\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 (3\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,084 (52\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLocation SHC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAmsterdam\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,315 (29\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e735 (30\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e580 (28\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eRotterdam\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e663 (14\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e402 (16\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e261 (12\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eUtrecht\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e469 (10\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e252 (10\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e217 (10\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNorthern Netherlands\u003c/em\u003e\u003csup\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e425 (9\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e221 (9\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e204 (9\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMiddle Netherlands\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e534 (11\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e236 (9\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e298 (14\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSouthern Netherlands\u003c/em\u003e\u003csup\u003e\u003cem\u003e3\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,082 (24\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e586 (24\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e496 (24\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (19, 22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (20, 23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (19, 21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e16\u0026ndash;18\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e655 (14\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e272 (11\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e383 (18\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e19\u0026ndash;21\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,373 (52\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,146 (47\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,227 (59\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e22\u0026ndash;24\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,460 (32\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,014 (41\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e446 (21\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMigration background\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNone (Dutch)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,522 (78\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,900 (78\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,622 (79\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMigrant\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e257 (5\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e128 (5\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e129 (6\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eChild of migrant\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e692 (15\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e390 (16\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e302 (14\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEducation\u003c/b\u003e\u003csup\u003e\u003cb\u003e4\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e(Pre)university\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,442 (76\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,874 (77\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,568 (76\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eOther\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,042 (23\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e556 (22\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e486 (23\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSelf-reported vaccination status\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eUnvaccinated\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,560 (34\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e934 (38\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e626 (30\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eVaccinated\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,928 (65\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,498 (61\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,430 (69\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePartner\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNo steady partner\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,917 (65\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,588 (65\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,329 (65\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSteady partner\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,395 (31\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e780 (32\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e615 (30\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eOpen relationship\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e132 (3\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (1\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e87 (4\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of hormonal contraceptive use\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNo\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e169 (3\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90 (5\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79 (2\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eYes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,163 (92\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,415 (90\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,748 (93\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eUnknown/missing\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e156 (3\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (3\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100 (3\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSexual behaviour\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eWSM\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,157 (92\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,283 (93\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,874 (91\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eWSW\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e331 (7\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e149 (6\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e182 (8\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge sexual debut (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (15, 17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (15, 17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (15, 17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge sexual debut (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e\u0026le;\u0026thinsp;14\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,745 (39\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e902 (37\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e843 (41\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e15\u0026ndash;16\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e581 (13\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e329 (13\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e252 (12\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e\u0026ge;\u0026thinsp;17\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,098 (47\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,175 (48\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e923 (45\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo. sex partners lifetime\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (4, 12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (4, 12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (4, 11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo. sex partners lifetime\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e0\u0026ndash;4\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,241 (27\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e612 (25\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e629 (30\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e5\u0026ndash;9\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,610 (36\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e858 (35\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e752 (36\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e\u0026ge;\u0026thinsp;10\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,592 (35\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e932 (38\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e660 (32\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo. sex partners preceding 6 mos.\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1, 4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1, 4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1, 3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo. sex partners preceding 6 mos.\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e0\u0026ndash;1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,189 (26\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e623 (25\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e566 (27\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2\u0026ndash;3\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,937 (65\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,603 (66\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,334 (64\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003e\u0026ge;\u0026thinsp;4\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e359 (8\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e203 (8\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e156 (7\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistory of STI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNo\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,239 (50\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,216 (50\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,023 (50\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eYes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,332 (29\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e739 (30\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e593 (29\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNever tested\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e890 (20\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e470 (19\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e420 (20\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrent Ct infection\u003c/b\u003e\u003csup\u003e\u003cb\u003e5\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNegative\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,682 (82\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,052 (84\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,630 (79\u0026middot;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePositive\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e775 (17\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e364 (15\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e411 (20\u0026middot;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrent Ng infection\u003c/b\u003e\u003csup\u003e\u003cb\u003e5\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNegative\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,367 (97\u0026middot;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,348 (96\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2,019 (98\u0026middot;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePositive\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (1\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (1\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (1\u0026middot;0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNot tested\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 (1\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 (2\u0026middot;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (0\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHPV-16/18\u003c/b\u003e\u003csup\u003e\u003cb\u003e6\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e299 (6\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e205 (8\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94 (4\u0026middot;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ehrHPV\u003c/b\u003e\u003csup\u003e\u003cb\u003e7\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,533 (56\u0026middot;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,427 (58\u0026middot;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,106 (53\u0026middot;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003e0\u0026middot;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNote: Eligibility for HPV vaccination is based on birth cohorts. Catch-up consisted of birth cohort 1993\u0026ndash;1996, routine vaccination of birth cohort\u0026thinsp;\u0026ge;\u0026thinsp;1997. P-value based on a chi-squared test for categorical variables and Wilcoxon rank-sum test for continuous, due to their non normal distributed nature. Totals may vary due to missings. Migration background: 17 missings; education: 4 missings; partner 44 missings; age sexual debut 64 missings; no. sexual partners lifetime 45 missings; no. sexual partners preceding 6 months: 3 missings.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eAbbreviations: Ct Chlamydia trachomatis; Ng Neisseria gonorrhoeae; hrHPV high-risk HPV; HPV human papilloma virus; IQR interquartile range; SHC sexual health clinic; STI sexually transmitted infection; WSM women having sex with men only; WSW women having sex with women.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e1: Multiple SHCs from the provinces Friesland, Groningen and Drenthe.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e2: Multiple SHCs from the provinces Overijssel and Gelderland.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e3: Multiple SHC from the provinces Noord-Brabant and Limburg.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e4: (Pre)university is defined as higher general secondary education, pre-university education, university for applied sciences and university. Other is defined as all other levels of education.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e5: Diagnosis at the same visit to the SHC at which the participant was included in this study.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e6: DNA-positive for at least one of HPV-16/18.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003e7: DNA-positive for at least one of HPV-16/18/31/33/35/39/45/51/52/56/58/59.\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOverall, 6.7% of the participants tested positive for HPV-16 and/or HPV-18 (n\u0026thinsp;=\u0026thinsp;299) and 56.4% for at least one hrHPV genotype (n\u0026thinsp;=\u0026thinsp;2,532) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The type-specific and grouped HPV prevalences for the twelve hrHPV genotypes and the lrHPV genotypes 6/11 by vaccination status can be found in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThere were important differences between women who had been vaccinated and those who had not been vaccinated (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Compared to unvaccinated women, vaccinated women were more likely to have no migration background, to have done (pre)university education, to have an older age at sexual debut and to have no history of STI. Compared to women who had been eligible for routine vaccination, those who had been eligible for catch-up HPV vaccination were more likely to be of older age at inclusion, to be unvaccinated, to have an older age at sexual debut, and higher number of sexual partners lifetime and preceding 6 months (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eVE estimates\u003c/h2\u003e \u003cp\u003eUnadjusted VE against at least one of the bivalent genotypes was 91.2% (95% confidence interval (CI): (87.9; 93.7). VE against HPV-16 was 92.7% (95%CI: (88.9; 95.4), and 88.5% (95%CI: (82.0; 93.0) against HPV-18. More details on other type-specific and grouped VE can be found in Supplementary table 2.\u003c/p\u003e \u003cp\u003eThe PS stratification adjusted VE against genital HPV-16 DNA-positivity was 93.5% (95%CI: 89.8; 95.9); for HPV-18 this was 89.5 (95%CI: 83.0; 93.6) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Next to the vaccine targeted genotypes, statistically significant protection was found against HPV-31 (63.9%; 95%CI: 54.1; 71.6), HPV-33 (51.5%; 95%CI: 32.6; 65.0), HPV-35 (48.5%; 95%CI: 23.0; 65.5), HPV-45 (79.6%; 95%CI: 64.7; 88.2), HPV-52 (18.0%; 95%CI: 6.2; 28.4) and HPV-58 (31.4%; 95%CI: 8.7; 48.5) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Significant negative VE was found against HPV-59: -42.6% (95%CI: -92.9; -5.4).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe VE against grouped genital DNA-positivity of at least one of the bivalent genotypes was 92.1% (95%CI: 88.9; 94.3). Grouped VE against any hrHPV was 12.8% (95%CI: 7.9; 17.4). More grouped estimates can be found in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStratified VE estimates\u003c/h2\u003e \u003cp\u003eNo statistically significant differences were found in VE estimates of the birth cohort that had been eligible for the catch-up campaign (birth cohort 1993\u0026ndash;1996, eligible at age 13\u0026ndash;16 years) and VE estimates of the birth cohort which had been eligible for routine HPV vaccination within the NIP (birth cohort\u0026thinsp;\u0026ge;\u0026thinsp;1997, eligible at age 12) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA, Supplementary table 3). VE against genital HPV-16 was 92.1% (95%CI: 86.6; 95.4) for the birth cohort of the catch-up campaign, and 94.9% (95%CI: 87.8; 97.8) for the birth cohort of routine vaccination (p for interaction\u0026thinsp;=\u0026thinsp;0.54). For HPV-18 this was 92.2% (95%CI: 84.1; 96.2) and 86.8 (95%CI: 74.0; 93.3) (p for interaction\u0026thinsp;=\u0026thinsp;0.37). More details can be found in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA and Supplementary table 3.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFor women who had been eligible for catch-up vaccination, stratified analyses by age of sexual debut relative to the year they had been offered HPV vaccination, i.e. by having been potentially sexually active at time of vaccination eligibility (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB, Supplementary table 4). VE estimates were slightly lower for five of the seven VE estimates for women who were sexually active before or in the same year as being eligible for vaccination, although none of these differences were statistically significant. The VE against genital HPV-16 and/or HPV-18 was 94.5% (95%CI: 89.9; 97.0) for women who were not sexually active before having been eligible for vaccination, and 87.5% (95%CI: 76.1; 93.4) for those who were sexually active before or at the same age as being eligible for vaccination (p for interaction 0.07).\u003c/p\u003e \u003cp\u003eIn the VE analyses stratified by number of sex partners in the preceding 6 months, and by years sexually active, also no significant differences were observed in type-specific and grouped VE between the strata (Supplementary Fig.\u0026nbsp;1).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSensitivity analyses:\u003c/h2\u003e \u003cp\u003eIn the sensitivity analyses, no differences were found in VE estimates between the two methods used for adjustment for differences in characteristic between vaccinated and unvaccinated women and differences in study population over the study rounds. Type-specific and grouped VE were comparable for unadjusted estimates, estimates adjustments with multivariable logistic regression, and estimates with PS stratification (Supplementary Fig.\u0026nbsp;2).\u003c/p\u003e \u003cp\u003e4002 women were included in the sensitivity analysis restricted to women who were offered a 3-dose vaccination schedule (all born in 1993\u0026ndash;2000), and 331 were excluded as they were born in 2001 or later. No statistically significant differences were observed between VE of the catch-up cohort and the routine vaccination cohort (Supplementary Fig.\u0026nbsp;3).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated a very high VE of the bivalent HPV vaccine against female genital HPV positivity for the targeted HPV genotypes HPV-16 and HPV-18 during the girls-only HPV vaccination period in the Netherlands. Significant cross-protection was found against 6 other hrHPV genotypes, being HPV-31, 33, 35, 45, 52 and 58. No significant differences were found in VE between women in our study who had been eligible for the 2009 catch-up campaign for girls aged 13\u0026ndash;16 and women who had been eligible for routine vaccination at age 12 as part of the Dutch NIP.\u003c/p\u003e \u003cp\u003eA strength of our study was the large study population, of whom 4,488 were included in the main analyses. This is substantially more than the preceding VE analysis based on PASSYON data of 1,087 women[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Additionally, data from multiple geographical locations were used, resulting in a high coverage and representativity for the country. Furthermore, the Dutch setting is uniquely suited to assess VE of the bivalent vaccine post-licencing, as the Netherlands is one of the few high-income countries that uses only the bivalent vaccine[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], and has done so since the start of HPV vaccination within the NIP. Lastly, the study population was aged 16\u0026ndash;24 years old, the age span in which the incidence of female genital HPV infections is at its peak[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSome limitations should be mentioned. First, several variables were self-reported, such as sexual behaviour and vaccination status, possibly leading to recall or social desirability bias. However, sexual behaviour is hard to measure otherwise, and previous analyses from the PASSYON study showed that self-reported vaccination status of women correlated very well with high antibody levels[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Second, vaccination status was not reported, or genital swab not provided by 518 women, who were otherwise eligible for analyses. This might have led to selection bias. Based on variables such as age, age at sexual debut and number of sexual partners, there is no indication to expect this. Third, the study population consisted of SHC clients. As these women are likely more sexually active than their peers not visiting SHCs, this might limit the generalizability of the results. Nevertheless, stratified analyses showed that VE estimates were comparable across strata of sexual behaviour, which favours generalizability. Fourth, to minimise confounding caused by differences in study populations between study rounds and vaccination status of women, we used PS stratification to adjust. Nevertheless, this only adjusts for measured variables. We had no information on type of sexual practices and smoking behaviour, so we were not able to adjust for these variables. Finally, we were unable to conduct a comparison of VE of administering two doses vs. three doses. Due the pseudonymized study design, we could not link our data to a national vaccination database. Considering evidence suggesting that a single dose provides comparable efficacy to three doses of bivalent HPV vaccination against HPV infection[\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], we would not expect large differences in VE between different doses groups. We therefore defined being vaccinated as 'having received at least one dose'.\u003c/p\u003e \u003cp\u003eThe VE estimates of type-specific and grouped VE against genital HPV-16 and/or HPV-18 of this study are in agreement with previous literature; the estimates are in line with previous vaccine efficacy trials of the bivalent HPV vaccine[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], and with post-licensing observational studies among young women[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Some of these studies assessed persistent infection instead of HPV positivity, but reported comparable VE estimates against female genital HPV.\u003c/p\u003e \u003cp\u003eWe found significant cross-protection against 6 genotypes, being HPV-31, 33, 35, 45, 52 and 58. These genotypes are associated with an additional 18% of cervical cancers worldwide[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Cross-protection against these genotypes had been observed before in HPV vaccine studies, although never before all these 6 genotypes within one study. The PATRICIA trial, the largest phase III trial, observed significant cross-protection against persistent infection with HPV-31, 33, 45 and 52 with comparable estimates, and against incident infection with HPV-35[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Another large clinical trial, the Costa Rica HPV vaccine Trial, assessed cross-protection of the bivalent HPV vaccine against incident infection[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. They observed not only cross-protection against previously mentioned genotypes (HPV-31/33/35/45), but also against HPV-58 of 21.2% (95%CI: 4.2; 35.3), somewhat lower than our estimate. In a systematic review on cross-protective effects of the bivalent HPV vaccine, outcomes of 17 observational studies were compared[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], either as VE or prevalence over time. Of these studies, being from Japan, Luxembourg, Scotland, Finland and the Netherlands, 11 observed cross-protection: nine against HPV-31, eight against HPV-45, five against HPV-31, and two against HPV-52[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Finally, a previous analysis of the PASSYON study[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] did not observe the significant cross-protection against HPV-33 and HPV-58 observed in our current analysis study, which is probably explained by the greater power of the current analyses due to the larger study population.\u003c/p\u003e \u003cp\u003eA statistically significant negative VE for HPV-59 was observed. The SPF\u003csub\u003e10\u003c/sub\u003e-DEIA-LiPA\u003csub\u003e25\u003c/sub\u003e is known to detect HPV-59 less well in the presence with co-infection of other hrHPV genotypes[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Effective vaccination leads to a decrease in co-infections with other genotypes, making it more likely for HPV-59 to be detected in vaccinated compared to unvaccinated women[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. This might lead to a biased VE estimate as shown previously[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, VE estimates were similar for women who had been eligible for the catch-up campaign in 2009 at the age 13\u0026ndash;16 years and for women who had been eligible from 2010 onwards for routine HPV vaccination at 12 years as part of the Dutch NIP. Even for women whom were potentially sexually active at the time they had been offered HPV vaccination, the VE was very high. Only one other study, also conducted in the Netherlands, compared routine vaccination to the catch-up, but did not report VE estimates[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. That study did not find different hrHPV positivity rates for women vaccinated in the catch-up campaign compared to those vaccinated in routine vaccination, in line with findings of the current study[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Our results are strongly suggestive that catch-up campaigns up to the age of 16 is probably as effective, in terms of VE, as routine vaccination at an earlier age. This is in line with other studies that found that vaccination up to age 16 years was associated with reduced risk of cervical cancer protection; protection was much lower for females vaccinated at the age of 17 years and above[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Therefore it seems that catch-up campaigns up to the age of 16 years might be most effective in terms of protection.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn our study a high VE of bivalent HPV vaccination was demonstrated against genital HPV-16 and HPV-18 DNA-positivity for young women in the Netherlands. Additionally, significant cross-protection was found for six other hrHPV genotypes. Together, these eight genotypes are responsible for 89% of cervical cancers worldwide. These findings should be used in cost-effectiveness studies when deciding about the choice of vaccine in NIPs. Moreover, this study demonstrated that catch-up campaigns focussed on girls up to age 16 years is likely to be as protective as routine vaccination at an earlier age.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eConfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ehrHPV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehigh\u0026ndash;risk HPV\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHPV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHuman papillomavirus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIPW\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInverse probability weighting\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterquartile range\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003elrHPV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elow\u0026ndash;risk HPV\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNIP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNational immunisation programme\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epropensity score\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRelative risk\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSHC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSexual health clinic\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSTI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSexually transmitted infection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVaccine effectiveness\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eThe PASSYON study group\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eHelmie van der Meijden, Karlijn Kampman, Elske Hoornenborg, Annet Bak, Marga Smit, Harriette van Buel, Ferna Neienhuijsen, Marlot Ippel, Dianne Schriemer, Inez Swart, and Denise Twisk.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgements\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the following for their valuable contributions to the design or execution of the study: Hein Boot (deceased), Elske van Logchem, Naomi van Marm, Suzan Leussink, Tim Severs, Rutger Schepp, Kahren van Eer, Thomas Langenburg, Najima Lamkaraf, Maarten Schipper, Petra Woestenberg, Rianne Vriend and Marianne van der Sande.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurthermore, the centres for sexual health, including all nurses and physicians, within the Public Health Services and the hospitals are acknowledged for their permission to collect data from their clients and for their efforts. The authors acknowledge the medical microbiologic laboratories and their staff for storage and testing of the samples.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by Medical Ethics Committee of the University of Utrecht, The Netherlands (reference number: 08/397). Participants gave informed consent to participate in the study before taking part.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis study collected data which has been pseudonymised. Pseudonymised individual participant data can be requested for scientific use with a methodologically sound proposal. In case of data sharing, receivers of data will need to sign a data transfer agreement.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe institution of\u0026nbsp;M.F. Schim van der Loeff and J.C.M Heijne received study funding for an investigator-initiated study from GSK. M.F. Schim van der Loeff served on advisory boards of MSD and Novosanis. All other authors report no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Ministry of Health, Welfare and Sport, the Netherlands. The funders had no role in study design, data collection and analysis, interpretation of data, decision to publish, or preparation of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthor\u0026rsquo;s contributions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eBH van Benthem was the principal investigator of the PASSYON study, and together with HE de Melker responsible for funding acquisition. AJ King was responsible for supervising the genital sample analyses and the interpretation of the HPV DNA-sample analyses. JMA Kusters, AJ King and BH van Benthem were responsible for validation and verification of the data. JMA Kusters, MF Schim van der Loeff, JCM Heijne and BHB van Benthem were responsible for the conception, methodology and design of the current study. JMA Kusters was responsible for conducting the formal analyses. All authors participated in the interpretation of the results. The original manuscript draft, including figures and tables, was created by JMA Kusters, and all authors contributed to editing of the manuscript and approving the final draft. Finally, BH van Benthem, JCM Heijne and MF Schim van der Loeff were responsible for supervising JMA Kusters.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ede Sanjose S, Brotons M, Pavon MA. The natural history of human papillomavirus infection. Best Pract Res Clin Obstet Gynecol. 2018;47:2\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017;141(4):664\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, Tous S, Felix A, Bravo LE, Shin H-R. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11(11):1048\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePaavonen J, Naud P, Salmer\u0026oacute;n J, Wheeler CM, Chow S-N, Apter D, Kitchener H, Castellsague X, Teixeira JC, Skinner SR. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet. 2009;374(9686):301\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown DR, Joura EA, Yen GP, Kothari S, Luxembourg A, Saah A, Walia A, Perez G, Khoury H, Badgley D. Systematic literature review of cross-protective effect of HPV vaccines based on data from randomized clinical trials and real-world evidence. Vaccine. 2021;39(16):2224\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMesher D, Panwar K, Thomas SL, Edmundson C, Choi YH, Beddows S, Soldan K. The impact of the national HPV vaccination program in England using the bivalent HPV vaccine: surveillance of type-specific HPV in young females, 2010\u0026ndash;2016. J Infect Dis. 2018;218(6):911\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePurri\u0026ntilde;os-Hermida MJ, Santiago-P\u0026eacute;rez MI, Trevi\u0026ntilde;o M, Dopazo R, Ca\u0026ntilde;izares A, Bonacho I, Trigo M, Fern\u0026aacute;ndez ME, Cid A, G\u0026oacute;mez D. Direct, indirect and total effectiveness of bivalent HPV vaccine in women in Galicia, Spain. PLoS ONE. 2018;13(8):e0201653.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKudo R, Yamaguchi M, Sekine M, Adachi S, Ueda Y, Miyagi E, Hara M, Hanley SJ, Enomoto T. Bivalent human papillomavirus vaccine effectiveness in a japanese population: High vaccine-type\u0026ndash;specific effectiveness and evidence of cross-protection. J Infect Dis. 2019;219(3):382\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLatsuzbaia A, Arbyn M, Tapp J, Fischer M, Weyers S, Pesch P, Mossong J. Effectiveness of bivalent and quadrivalent human papillomavirus vaccination in Luxembourg. Cancer Epidemiol. 2019;63:101593.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDonken R, King AJ, Bogaards JA, Woestenberg PJ, Meijer CJLM, de Melker HE. High Effectiveness of the Bivalent Human Papillomavirus (HPV) Vaccine Against Incident and Persistent HPV Infections up to 6 Years After Vaccination in Young Dutch Women. J Infect Dis. 2018;217(10):1579\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWoestenberg PJ, King AJ, van Benthem BH, Donken R, Leussink S, van der Klis FR, de Melker HE, van der Sande MA, Hoebe CJ, Bogaards JA. Bivalent vaccine effectiveness against type-specific HPV positivity: evidence for cross-protection against oncogenic types among Dutch STI clinic visitors. J Infect Dis. 2018;217(2):213\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMollers M, King AJ, Knol MJ, Scherpenisse M, Meijer CJ, van der Klis FR, de Melker HE. Effectiveness of human papillomavirus vaccine against incident and persistent infections among young girls: results from a longitudinal Dutch cohort study. Vaccine. 2015;33(23):2678\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCameron RL, Kavanagh K, Pan J, Love J, Cuschieri K, Robertson C, Ahmed S, Palmer T, Pollock KG. Human papillomavirus prevalence and herd immunity after introduction of vaccination program, Scotland, 2009\u0026ndash;2013. Emerg Infect Dis. 2016;22(1):56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCuschieri K, Kavanagh K, Moore C, Bhatia R, Love J, Pollock KG. Impact of partial bivalent HPV vaccination on vaccine-type infection: a population-based analysis. Br J Cancer. 2016;114(11):1261\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCody P, Tobe K, Abe M, Elbasha EH. Public health impact and cost effectiveness of routine and catch-up vaccination of girls and women with a nine-valent HPV vaccine in Japan: a model-based study. BMC Infect Dis. 2021;21(1):1\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDrolet M, Laprise J-F, Brotherton JM, Donovan B, Fairley CK, Ali H, B\u0026eacute;nard \u0026Eacute;, Martin D, Brisson M. The impact of human papillomavirus catch-up vaccination in Australia: implications for introduction of multiple age cohort vaccination and postvaccination data interpretation. J Infect Dis. 2017;216(10):1205\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaniels V, Prabhu VS, Palmer C, Samant S, Kothari S, Roberts C, Elbasha E. Public health impact and cost-effectiveness of catch-up 9-valent HPV vaccination of individuals through age 45 years in the United States. Hum Vaccin Immunother. 2021;17(7):1943\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoes J, Schurink T, van\u0026rsquo;t Klooster HP, van der Weele P, van Eer K, Woestenberg P, van Benthem B, Boogaards H, van der Klis F, King A. HPV-​ vaccinatie in Nederland: 10 jaar in het Rijksvaccinatieprogramma, een overzicht. Nederlands tijdschrift voor medische microbiologie. 2019;27(4):226\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVriend HJ, Boot HJ, van der Sande MA. Type-specific human papillomavirus infections among young heterosexual male and female STI clinic attendees. Sex Transm Dis 2012:72\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWoestenberg PJ, King AJ, Van Benthem BH, Leussink S, Van der Sande MA, Hoebe CJ, Bogaards JA, Laboratories MM. Services tPH: Bivalent vaccine effectiveness against anal human papillomavirus positivity among female sexually transmitted infection clinic visitors in the Netherlands. J Infect Dis. 2020;221(8):1280\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWoestenberg PJ, King AJ, van der Sande MA, Donken R, Leussink S, van der Klis FR, Hoebe CJ, Bogaards JA, van Benthem BH, Adema D. No evidence for cross-protection of the HPV-16/18 vaccine against HPV-6/11 positivity in female STI clinic visitors. J Infect. 2017;74(4):393\u0026ndash;400.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalag\u0026oacute;n T, Drolet M, Boily M-C, Franco EL, Jit M, Brisson J, Brisson M. Cross-protective efficacy of two human papillomavirus vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12(10):781\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRubin DB. Propensity score methods. Am J Ophthalmol. 2010;149(1):7\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70(1):41\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen JW, Maldonado DR, Kowalski BL, Miecznikowski KB, Kyin C, Gornbein JA, Domb BG. Best practice guidelines for propensity score methods in medical research: consideration on theory, implementation, and reporting. A review. Arthroscopy: J Arthroscopic Relat Surg. 2022;38(2):632\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDiaz-Quijano FA. A simple method for estimating relative risk using logistic regression. BMC Med Res Methodol. 2012;12:1\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElfstr\u0026ouml;m KM, Dillner J, Arnheim-Dahlstr\u0026ouml;m L. Organization and quality of HPV vaccination programs in Europe. Vaccine. 2015;33(14):1673\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSerrano B, Brotons M, Bosch FX, Bruni L. Epidemiology and burden of HPV-related disease. Best Pract Res Clin Obstet Gynecol. 2018;47:14\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKreimer AR, Herrero R, Sampson JN, Porras C, Lowy DR, Schiller JT, Schiffman M, Rodriguez AC, Chanock S, Jimenez S. Evidence for single-dose protection by the bivalent HPV vaccine\u0026mdash;review of the Costa Rica HPV vaccine trial and future research studies. Vaccine. 2018;36(32):4774\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarnabas RV, Brown ER, Onono MA, Bukusi EA, Njoroge B, Winer RL, Galloway DA, Pinder LF, Donnell D, Wakhungu N. Durability of single-dose HPV vaccination in young Kenyan women: randomized controlled trial 3-year results. Nat Med. 2023;29(12):3224\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWatson-Jones D, Changalucha J, Whitworth H, Pinto L, Mutani P, Indangasi J, Kemp T, Hashim R, Kamala B, Wiggins R. Immunogenicity and safety of one-dose human papillomavirus vaccine compared with two or three doses in Tanzanian girls (DoRIS): an open-label, randomised, non-inferiority trial. Lancet Global Health. 2022;10(10):e1473\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarper DM, Franco EL, Wheeler CM, Moscicki A-B, Romanowski B, Roteli-Martins CM, Jenkins D, Schuind A, Clemens SAC, Dubin G. Sustained efficacy up to 4\u0026middot; 5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet. 2006;367(9518):1247\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWheeler CM, Castellsagu\u0026eacute; X, Garland SM, Szarewski A, Paavonen J, Naud P, Salmer\u0026oacute;n J, Chow S-N, Apter D, Kitchener H. Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012;13(1):100\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStruyf F, Colau B, Wheeler CM, Naud P, Garland S, Quint W, Chow S-N, Salmer\u0026oacute;n J, Lehtinen M, Del Rosario-Raymundo MR. Post hoc analysis of the PATRICIA randomized trial of the efficacy of human papillomavirus type 16 (HPV-16)/HPV-18 AS04-adjuvanted vaccine against incident and persistent infection with nonvaccine oncogenic HPV types using an alternative multiplex type-specific PCR assay for HPV DNA. Clin Vaccine Immunol. 2015;22(2):235\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsang SH, Sampson JN, Schussler J, Porras C, Wagner S, Boland J, Cortes B, Lowy DR, Schiller JT, Schiffman M. Durability of cross-protection by different schedules of the bivalent HPV vaccine: the CVT trial. JNCI: J Natl Cancer Inst. 2020;112(10):1030\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Eer K, Leussink S, Severs TT, van Marm-Wattimena N, Woestenberg PJ, Bogaards JA, King AJ. Evidence for missing positive results for human papilloma virus 45 (HPV-45) and HPV-59 with the SPF10-DEIA-LiPA25 (version 1) platform compared to type-specific real-time quantitative PCR assays and impact on vaccine effectiveness estimates. J Clin Microbiol. 2020;58(11). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1128/jcm\u003c/span\u003e\u003cspan address=\"10.1128/jcm\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 01626\u0026thinsp;\u0026ndash;\u0026thinsp;01620.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchurink-van\u0026rsquo;t Klooster TM, Siebers AG, Hoes J, van Kemenade FJ, Berkhof J, Bogaards JA, de Melker HE. Early effect of bivalent human papillomavirus vaccination on cytology outcomes in cervical samples among young women in the Netherlands. Cancer Med. 2023;12(10):11786\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKjaer SK, Dehlendorff C, Belmonte F, Baandrup L. Real-World Effectiveness of Human Papillomavirus Vaccination Against Cervical Cancer. JNCI: J Natl Cancer Inst. 2021;113(10):1329\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLei J, Ploner A, Elfstr\u0026ouml;m KM, Wang J, Roth A, Fang F, Sundstr\u0026ouml;m K, Dillner J, Spar\u0026eacute;n P. HPV vaccination and the risk of invasive cervical cancer. N Engl J Med. 2020;383(14):1340\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmed","sideBox":"Learn more about [BMC Medicine](http://bmcmedicine.biomedcentral.com/)","snPcode":"12916","submissionUrl":"https://submission.nature.com/new-submission/12916/3","title":"BMC Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"human papillomavirus, vaccine effectiveness, prophylactic vaccination, bivalent vaccine, catch-up campaign, observational study, propensity score","lastPublishedDoi":"10.21203/rs.3.rs-4330011/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4330011/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe Netherlands is one of few countries worldwide which has used the bivalent HPV vaccine for girls-only for over a decade. This allows assessment of vaccine effectiveness (VE) against female genital HPV DNA-positivity of this vaccine in an observational post-licensing real-world setting. Additionally, it is unclear whether catch-up vaccination campaigns result in similar VE as routine vaccination. Therefore, type-specific and grouped VE were assessed and compared for women who had been eligible for catch-up vaccination at 13\u0026ndash;16 years with those who had been eligible for routine vaccination at 12 years.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePASSYON is a Dutch biennial repeated cross-sectional (2011-21) study among sexual health clinic clients aged 16\u0026ndash;24 years old. Women provided self-collected vaginal samples, questionnaires on demographics and sexual behaviour were administered, and women self-reported HPV vaccination status. Samples were analysed using a PCR-based assay (SPF\u003csub\u003e10\u003c/sub\u003e-LiPA\u003csub\u003e25\u003c/sub\u003e). Type-specific and grouped VE estimates, adjusted with propensity score stratification, were assessed against genital positivity for 14 HPV-types. VE for targeted and non-targeted genotypes were compared between women who had been eligible for the catch-up and those who had been eligible for routine vaccination.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe study included 4,488 female participants who had been eligible for HPV vaccination and provided genital swabs (1,561 eligible for catch-up, 2,927 for routine vaccination). Very high VE against genital HPV-16 and HPV-18 was observed (resp. 93.5% and 89.5%) and significant cross-protection against six other genotypes (HPV-31/33/35/45/52/58), varying from 18.0% (HPV-52) to 79.6% (HPV-45). VE estimates were comparable between women who had been eligible for the catch-up campaign and those eligible for routine vaccination: VE HPV-16/18: 92.2% (95%CI: 87.9\u0026ndash;94.9) vs. 91.8% (95%CI: 86.0-95.2).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn real-world settings, the VE of bivalent vaccine is high against targeted genotypes, with cross-protection against 6 other genotypes. Catch-up campaigns up to age 16 years can be as effective as routine vaccination at age 12. This may inform countries considering catch-up campaigns when introducing or extending the use of HPV vaccination within their national immunisation programmes.\u003c/p\u003e","manuscriptTitle":"Vaccine Effectiveness Of Bivalent HPV Vaccination Against Genital HPV Of A Catch-Up Campaign And 12 Years Routine Vaccination For Girls-Only: A Biennial Repeated Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-19 19:32:27","doi":"10.21203/rs.3.rs-4330011/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-11T11:04:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-19T20:00:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-19T13:40:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"241937668020899677846009656492429360153","date":"2024-06-10T21:53:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"52188086783152348905619682296032337153","date":"2024-06-10T05:01:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"159898277373184702656602534597283996450","date":"2024-05-22T16:30:58+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-07T11:58:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-29T09:09:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-29T08:43:05+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Medicine","date":"2024-04-26T13:32:34+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmed","sideBox":"Learn more about [BMC Medicine](http://bmcmedicine.biomedcentral.com/)","snPcode":"12916","submissionUrl":"https://submission.nature.com/new-submission/12916/3","title":"BMC Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4effdbb7-84c4-4282-b481-0d31950f84e8","owner":[],"postedDate":"July 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-21T16:01:43+00:00","versionOfRecord":{"articleIdentity":"rs-4330011","link":"https://doi.org/10.1186/s12916-024-03686-4","journal":{"identity":"bmc-medicine","isVorOnly":false,"title":"BMC Medicine"},"publishedOn":"2024-10-15 15:57:31","publishedOnDateReadable":"October 15th, 2024"},"versionCreatedAt":"2024-07-19 19:32:27","video":"","vorDoi":"10.1186/s12916-024-03686-4","vorDoiUrl":"https://doi.org/10.1186/s12916-024-03686-4","workflowStages":[]},"version":"v1","identity":"rs-4330011","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4330011","identity":"rs-4330011","version":["v1"]},"buildId":"CiT4i_kKBbxQbnFL0ufpk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}