Effect of vaccination against HPV in the HPV-positive patients not covered by primary prevention on the disappearance of infection.

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Pruski Dominik, Millert-Kalińska Sonja, Jach Robert, Przybylski Marcin This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4594994/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Apr, 2025 Read the published version in Scientific Reports → Version 1 posted 15 You are reading this latest preprint version Abstract An undeniable risk factor for cervical cancer and intraepithelial neoplasia is persistent infection with HPV – types: 16,18, 31, 45, 52 and others. Changes in sexual behavior may in the coming decades influence the epidemiology of HPV-related lesions. For those diseases, vaccination against HPV may be the only effective mean of prevention. Our study aims to show the results and changes in the smear for HPV DNA in patients after receiving a vaccination course with a 9-valent HPV vaccine in women with HPV infection. Out of 320 subjects, with HPV- positive result 250 (78.1%) decided to be vaccinated against HPV and 70 (21.9%) did not. In the vaccinated group the rate of HPV disappearance was significantly higher over the follow-up period than in the control group. This applies especially to the complete disappearance of the HPV - in 72.4% vaccinated women compared to 45.7% unvaccinated. This effect is especially visible when analyzing the disappearance of HPV genotypes covered by the 9-valent vaccine. A significant disappearance of HPV infection occurs in patients both diagnosed due to HPV and undergoing LEEP-conization due to HSIL. Vaccination of this group of women will probably reduce the occurrence of different HPV-related lesions. Biological sciences/Immunology/Vaccines Health sciences/Oncology Health sciences/Health care/Public health/Population screening HPV vaccination 9-valent vaccination HPV infection treatment of HPV HPV-related disease SIL 1. Introduction Cervical cancer (CC) remains a significant global health challenge despite being theoretically preventable. It ranks as the fourth most common malignancy in women worldwide. In 2020 alone, there were an estimated 604,000 new cases and 342,000 deaths attributed to this disease [1]. An undeniable risk factor for cervical cancer and intraepithelial neoplasia is persistent infection with the human papillomavirus (HPV) – not only genotypes 16 and 18, but also: 31, 45, 52. Infections with oncogenic HPV genotypes include not only lesions of the cervix, but also pre-cancerous conditions and cancers of the head and neck, vagina, vulva, anus, and penis. Detection and treatment of LSIL-CIN 1, HSIL-CIN 2 and CIN 3 lesions is now simple and widely available. The availability of numerous diagnostic tests, including the self-sampling option, and the low invasiveness of colposcopic examination mean that these tests are most often performed on an outpatient basis. The LEEP-conization procedure, which involves excising the lesion without or with the entire transformation zone, is a simple procedure that does not require the conditions of an operating room and can be performed by any trained gynecologist. Currently, a greater challenge is the diagnosis and treatment of HPV-related lesions including lesions in the vagina, vulva, and anus. Removal of this type of lesions is often not radical or impossible because the topography is too close to the bladder or rectum and carries a very high risk of damaging other organs and creating a fistula. The use of preventive vaccines in the population of sexually initiated women, including HPV-positive women, may facilitate remission of the HPV virus, create immunological immunity, and reduce the occurrence of SIL-type lesions, mainly in ​​the cervix, vagina, vulva, and anus. Due to the discovery and implementation of preventive vaccinations against HPV, many countries are on the way to eliminating HPV-related cancers and diseases. Examples include New Zealand and Australia, Scandinavia, and Great Britain. In addition to population vaccination, these countries are also introducing solutions for the adult population - such as opportunistic HPV vaccination at universities. In fact, despite studies showing consistent results in the direction of efficacy, there is still skepticism in the scientific community about the use of the HPV vaccine as an adjuvant therapy, after local treatment, against relapses and in HPV-positive population after sexual initiation. Individuals with human papillomavirus (HPV)-related disease remain at risk for subsequent HPV infection and related disease after treatment of specific lesions. Additionally, patients treated for HPV-related high-grade histologic lesions have a significantly increased risk of developing HPV-related malignancies in the 20 years following treatment compared with the general population [2, 3]. More and more voices appear in the scientific and social debate, not only in the context of the preventive role of vaccination against HPV. The world is moving forward, now in the so-called "post-HPV vaccination era" - this is the time when the first patients vaccinated prophylactically at the age of 14 reached the common age for the development of CIN - studies and meta-analyses show what the risk is for these patients in terms of the development of HPV-dependent lesions. There are no documented contraindications to vaccination against HPV in people with current HPV infection [4, 5]. Additionally, people with previously diagnosed HPV infection have an increased risk of recurrence of HPV-related lesions, even after surgical treatment [6, 7, 8]. What is more, not only children and young adults decide to get vaccinated - but also adult women and men. This is a dimension of mutual responsibility between couples. Evidence also shows the value of vaccinating people who are immunosuppressed and infected with human immunodeficiency virus (HIV). People with warts and condylomas developing because of infection with non-oncogenic HPV types are vaccinated - although there is no hard evidence to reduce the risk of recurrence [9, 10]. Changes in sexual customs and behavior in both women and men may in the coming decades influence the epidemiology of HPV-related cancers and diseases occurring in the nasopharynx, larynx, vagina, vulva, cervix, and anus. In these population groups, the vaccine may be the only effective mean of prevention. It is worth mentioning how difficult it is to obtain an appropriate amount of material for molecular tests and how difficult it is to detect and recognize pre-cancerous lesions of the SIL type that do not occur in the cervix. Secondary prevention tools beyond the cervix are non-existent. Since strictly therapeutic vaccines are still in the research phase and are not commercially available, many adults infected with HPV have undergone vaccination against HPV. It should be emphasized that the use of the vaccine should be an additional measure and therapeutic procedures cannot be abandoned in justified cases, such as HSIL changes. However, the population of people willing to vaccinate in adulthood is constantly increasing thanks to growing public awareness. In recent years, reports have begun to appear regarding the beneficial effect of vaccination, the possibility of reducing the risk of recurrence of lesions, and the potential impact on the disappearance of HPV. This study aims to show the results and changes in the smear for HPV DNA in patients after receiving a vaccination course with a 9-valent HPV vaccine in women with HPV infection diagnosed in a cervical smear and this is an extended study of work published last year. 2. Methodology 2.1. Study design We provide a prospective, ongoing, non-randomized study to provide the effect of nine-valent HPV vaccination in HPV-positive patients with Gardasil®9 recombinant, nine-valent vaccine. This study was performed in line with the principles of the Declaration of Helsinki. The Bioethical Committee approved the study protocol (95/2021). We obtained written consent for the study from all patients. All subjects reported to a private gynecological practice focused and specialized in cervical cancer diagnosis in the years 2020–2023. This is a group of patients who called for in-depth diagnostics due to a positive HPV HR test result and/or an abnormal cytological result. To verify the final diagnosis, the patients underwent colposcopy with cervical biopsy and curettage of the cervical canal. To enhance the immunological response, all subjects were offered vaccination against HPV with the nine-valent vaccine in the 0-2-6 scheme. Out of 320 patients, 250 (78.1%) decided to be vaccinated and 70 (21.9%) did not. The inclusion criteria comprised: Adult females only. Non-pregnant or postpartum individuals. Subjects not undergoing immunosuppressive drug treatment. No prior vaccination with other HPV vaccines. Expressing informed written consent to participate. Consenting to proposed surgical diagnostics and potential surgical excision treatment if indicated. Having received three doses of the nine-valent HPV vaccination following the 0- 2- 6 month schedule. The exclusion criteria were as follows: 1. Refusal of potential treatment for squamous intraepithelial lesions. 2. Failure to complete the full vaccination regimen. The analysis is the last chance to assess the effect of adjuvant anti-HPV vaccination in the population not vaccinated in adolescence, because a generation that was more likely to be covered by primary prevention programs is entering adulthood. All patients with histopathologically confirmed high-grade squamous intraepithelial lesions (CIN 2+) were treated according to the current recommendations of the Polish Colposcopic Society, with the loop electrosurgical excision procedure (LEEP), and then subjected to strict control every six months. The control group includes seventy HPV-positive patients diagnosed with pre-neoplastic lesions who decided not to receive the HPV vaccine. 2.2. LBC, HPV genotyping and colposcopy with punch biopsy The cervix and endocervix material were collected with a Cyto-Brush and placed in a liquid medium PreservCyt® (Roche Diagnostic Systems, Meylan, France). Then, we performed PCR followed by a DNA enzyme immunoassay with a reverse hybridization line probe assay for HPV detection. To characterize HPV-positive samples, sequence analysis was performed. We used Roche Linear Array HPV Genotyping Test®, which identifies 32 HPV DNA of the following genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 (high-risk genotypes); 26, 53, 66, 70, 73 and 82 (probable high-risk genotypes); and 6, 11, 40, 42, 43, 44, 54, 61, 62, 67, 81, 83 and 89 (low-risk genotypes) or the BD Onclarity HPV Assay detecting 14 different HPV genotypes while incorporating a β-globininternal control (IC) as a processing control. The HPV genotypes that can be detected individually are HPV 16, 18, 31, 45, 51, and 52. The remaining genotypes are grouped as follows: HPV 33/58, 56/59/66, and 35/39/68. The IC serves as a control to ensure the accuracy and validity of the assay. Colposcopy was performed in case of: (1) abnormal cervical image under gynecological examination; (2) abnormal LBC result, i.e., ASC-US, AGC, LSIL, ASC-H, HSIL, cervical cancer; and (3) positive high-risk HPV test result (genotype 16, 18 or 31). The colposcopy was performed according to the International Federation of Cervical Pathology and Colposcopy classification. In all cases, at least one cervix biopsy from transformation zone (TZ) and cervical canal curettage was taken. 2.3. Statistical analysis Analysis was conducted with statistical software R, version R4.1.2. All analyses assumed significance level of α = 0.05. Nominal variables were presented as n and %, age was summarised with mean and standard deviation. Dependencies between categorical variables were analysed with Pearson’s Chi-square test or Fisher’s exact test, as appropriate. Comparison of age as numeric variable between study groups was conducted with t-Student test. Normality of distributions was assessed with Shapiro-Wilk test, skewness and kurtosis. Variance homogeneity was assessed with Levene’s test. 3. Results 3.1. Study groups characteristics and comparison Study groups characteristics were presented in Table 1 . Patients from both study groups did not differ in age, cytology outcome, HPV genotypes before vaccination, biopsy outcome, and LEEP/surgery outcome (p > 0.05). HPV outcomes after vaccination differentiated the groups. Vaccinated group had significantly lower proportion of positive outcome for any HPV genotype (27.6% vs 54.3% in control group), p < 0.001. Vaccinated group had significantly lower proportion of positive outcome for HPV Gardasil genotype (14.8% vs 40.0% in control group), p < 0.001. Vaccination/observation outcome described by 5-category scale was significantly different between groups, p < 0.001. Proportion of patients with same genotypes after vaccination was lower in Vaccinated group (6.4% vs 32.9% in control group). Proportion of patients with partially same genotypes after vaccination was lower in Vaccinated group (5.2% vs 8.6%). Complete remission rate was higher in Vaccinated group (72.4% vs 45.7%). Proportion of new infections was higher in Vaccinated group (12.4% vs 5.7%) and proportion of patients with same/partially same genotype and new infection was higher in Vaccinated group (3.6% vs 7.1% in control group). Table 1 Characteristics and comparison of study groups Characteristics Vaccinated group Control group MD (95% CI) p N 250 (100.0) 70 (100.0) - - Age, years, mean ± SD 32.72 ± 6.56 32.50 ± 6.69 0.22 (-1.55;2.00) 0.803 1 Age, years, n (%) < 25 20 (8.0) 10 (14.3) - 0.110 2 < 35 149 (59.6) 33 (47.1) ≥ 35 81 (32.4) 27 (38.6) Cytology, n (%) NILM 40 (16.0) 12 (17.1) - 0.831 AS-CUS 33 (13.2) 14 (20.0) LSIL 88 (35.2) 25 (35.7) ASC-H 47 (18.8) 11 (15.7) HSIL 34 (13.6) 7 (10.0) AGC 6 (2.4) 1 (1.4) Cancer 2 (0.8) 0 (0.0) HPV Gardasil genotype, n (%) Positive 207 (82.8) 54 (77.1) - 0.366 Negative 43 (17.2) 16 (22.9) HPV genotype, n (%)* 6 23 (9.2) 1 (1.4) - 0.054 2 11 5 (2.0) 0 (0.0) - 0.590 16 109 (43.6) 37 (52.9) - 0.215 2 18 37 (14.8) 4 (5.7) - 0.071 2 31 40 (16.0) 10 (14.3) - 0.871 2 33 14 (5.6) 3 (4.3) - > 0.999 35 7 (2.8) 0 (0.0) - 0.354 39 13 (5.2) 2 (2.9) - 0.537 40 1 (0.4) 0 (0.0) - > 0.999 42 8 (3.2) 2 (2.9) - > 0.999 43 3 (1.2) 0 (0.0) - > 0.999 44 1 (0.4) 0 (0.0) - > 0.999 45 13 (5.2) 1 (1.4) - 0.318 51 23 (9.2) 7 (10.0) - > 0.999 2 52 19 (7.6) 6 (8.6) - 0.987 2 53 15 (6.0) 6 (8.6) - 0.621 2 54 6 (2.4) 3 (4.3) - 0.416 55 2 (0.8) 0 (0.0) - > 0.999 56 18 (7.2) 8 (11.4) - 0.370 2 58 9 (3.6) 2 (2.9) - > 0.999 59 8 (3.2) 2 (2.9) - > 0.999 61 7 (2.8) 1 (1.4) - > 0.999 62 11 (4.4) 2 (2.9) - 0.741 66 11 (4.4) 7 (10.0) - 0.082 67 11 (4.4) 1 (1.4) - 0.475 68 7 (2.8) 2 (2.9) - > 0.999 70 4 (1.6) 3 (4.3) - 0.180 73 9 (3.6) 1 (1.4) - 0.697 81 4 (1.6) 2 (2.9) - 0.615 82 8 (3.2) 2 (2.9) - > 0.999 83 2 (0.8) 0 (0.0) - > 0.999 84 3 (1.2) 0 (0.0) - > 0.999 87 1 (0.4) 0 (0.0) - > 0.999 89 2 (0.8) 1 (1.4) - 0.524 90 3 (1.2) 0 (0.0) - > 0.999 CP6108 3 (1.2) 0 (0.0) - > 0.999 CP6109 1 (0.4) 0 (0.0) - > 0.999 P1 2 (0.8) 0 (0.0) - > 0.999 P2 5 (2.0) 0 (0.0) - 0.590 P3 4 (1.6) 1 (1.4) - > 0.999 Biopsy, n (%) LSIL 57 (22.8) 12 (17.1) - 0.669 HSIL 115 (46.0) 32 (45.7) Adenocarcinoma 4 (1.6) 0 (0.0) Cancer 2 (0.8) 0 (0.0) No pathology 55 (22.0) 21 (30.0) No indication 17 (6.8) 5 (7.1) LEEP/surgery, n (%) LSIL 18 (7.2) 1 (1.4) - 0.325 2 HSIL 93 (37.2) 26 (37.1) Adenocarcinoma/cancer 6 (2.4) 1 (1.4) No pathology 31 (12.4) 7 (10.0) No indication 102 (40.8) 35 (50.0) LEEP/surgery, n (%) Any outcome 148 (59.2) 35 (50.0) - 0.216 2 No indication 102 (40.8) 35 (50.0) HPV any genotype, after vac., n (%) Positive 69 (27.6) 38 (54.3) - < 0.001 2 Negative 181 (72.4) 32 (45.7) HPV Gardasil genotype, after vac., n (%) Positive 37 (14.8) 28 (40.0) - < 0.001 2 Negative 213 (85.2) 42 (60.0) Category (before vs after vac.), n (%) Same genotype 16 (6.4) 23 (32.9) - < 0.001 2 Partially same genotype 13 (5.2) 6 (8.6) Complete remission 181 (72.4) 32 (45.7) New infection 31 (12.4) 4 (5.7) Same/partially same genotype and new infection 9 (3.6) 5 (7.1) SD – standard deviation, MD – mean difference (Gardasil group vs control group), n -number, CI – confidence interval; ASC-US — atypical squamous cells of undetermined significance; AGC — atypical glandular cells; ASC-H — atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion; LSIL — low-grade squamous intraepithelial lesion; HSIL — high-grade squamous intraepithelial lesion; HPV — human papillomavirus; NILM — negative for intraepithelial lesion or malignancy; LBC —liquid-based cytology; P1 - HPV 33/58; P2 – HPV 56/59/66; P3–35/39/68; LEEP- loop electrosurgical excision procedure; vac – vaccination. Groups compared with t-Student test 1 , Pearson’s Chi-square test 2 or Fisher’s exact test, as appropriate. * Various genotypes could be observed for one patient. 3.2. Dependencies between age and HPV +/- after vaccination as well as between LEEP/surgery outcome and HPV +/- after vaccination In Vaccinated group HPV outcome after vaccination was significantly dependant on LEEP/surgery outcome. Proportion of no indication to LEEP/surgery was significantly higher among patients with positive HPV after vaccination compared to negative HPV after vaccination (59.4% vs 33.7%), p < 0.001. Structure of LEEP/surgery detailed outcome was significantly different between positive and negative HPV after surgery, p = 0.005, with main difference lying in proportion of HSIL, which was lower among patients with positive HPV outcome (21.7% vs 43.1% among patients with negative HPV outcome after vaccination). Dependence of age and HPV outcome after vaccination was not confirmed (p = 0.163). In control group dependencies between age and HPV outcome after vaccination as well as between LEEP/surgery outcome and HPV outcome after vaccination were not confirmed (p > 0.05), Table 2 . Table 2 Dependencies between HPV outcome after vaccination and age and between HPV outcome after vaccination and LEEP/surgery outcome Characteristics Vaccinated group Control group HPV any genotype after vac. p HPV any genotype after vac. p Positive Negative Positive Negative Age, years, n (%) < 25 9 (13.0) 11 (6.1) 0.163 6 (15.8) 4 (12.5) 0.424 < 35 37 (53.6) 112 (61.9) 20 (52.6) 13 (40.6) ≥ 35 23 (33.3) 58 (32.0) 12 (31.6) 15 (46.9) LEEP/surgery, n (%) LSIL 4 (5.8) 14 (7.7) 0.005 0 (0.0) 1 (3.1) 0.161 1 HSIL 15 (21.7) 78 (43.1) 11 (28.9) 15 (46.9) Adenocarcinoma/cancer 1 (1.4) 5 (2.8) 1 (2.6) 0 (0.0) No pathology 8 (11.6) 23 (12.7) 3 (7.9) 4 (12.5) No indication 41 (59.4) 61 (33.7) 23 (60.5) 12 (37.5) LEEP/surgery, n (%) Any outcome 28 (40.6) 120 (66.3) < 0.001 15 (39.5) 20 (62.5) 0.093 No indication 41 (59.4) 61 (33.7) 23 (60.5) 12 (37.5) Groups compared with Pearson’s Chi-square test or Fisher’s exact test 1 , as appropriate. n – number; LSIL — low-grade squamous intraepithelial lesion; HSIL — high-grade squamous intraepithelial lesion; LEEP- loop electrosurgical excision procedure; vac – vaccination. 3.3. Dependencies between HPV (Gardasil type) +/- before vaccination and HPV +/- after vaccination In Gardasil group proportion of positive HPV outcomes after vaccination did not depend on proportion of positive outcomes of HPV Gardasil genotype before vaccination, both in perspective of any HPV genotype after vaccination and Gardasil HPV genotype after vaccination (p = 0.890 and p = 0.176, respectively). In control group no difference between groups with and without HPV Gardasil genotype before vaccination/observation was observed in proportion of positive HPV of any genotype after vaccination/observation (p = 0.069). Proportion of positive HPV Gardasil genotype after vaccination/observation was higher in group with positive HPV Gardasil genotype before vaccination/observation (51.9% vs 0.0% in group without HPV Gardasil genotype before vaccination/observation), p = 0.001, Table 3 . Table 3 Dependence between HPV outcomes before vaccination (Gardasil genotype) and HPV outcomes after vaccination Characteristics Vaccinated group Control group HPV Gardasil genotype before vac. p HPV Gardasil genotype before vac. p Positive Negative Positive Negative HPV any genotype, after vac., n (%) Positive 58 (28.0) 11 (25.6) 0.890 33 (61.1) 5 (31.2) 0.069 Negative 149 (72.0) 32 (74.4) 21 (38.9) 11 (68.8) HPV Gardasil genotype, after vac., n (%) Positive 34 (91.9) 173 (81.2) 0.176 28 (51.9) 0 (0.0) 0.001 Negative 3 (8.1) 40 (18.8) 26 (48.1) 16 (100.0) HPV — human papillomavirus; vac – vaccination. Groups compared with Pearson’s Chi-square test. Dependencies between age and category as well as between LEEP/surgery outcome and category In Gardasil group category of HPV outcome after vaccination was significantly related to LEEP/surgery outcome. Proportion of no indication to LEEP/surgery was the highest among patients with same genotype after vaccination (87.5%), lower among patients with new infection (54.8%), partially same genotype (46.2%, n = 6) and same/partially same genotype with new infections (44.4%, n = 4). Proportion of no indication was the lowest among patients with complete remission (33.7%), p = 0.041. Detailed LEEP/surgery outcome was significantly related to category of HPV outcome after vaccination, p = 0.048. Main differences were observed in proportion of HSIL and proportion of no pathology. Proportion of HSIL was the highest among patients with same/partially same genotype and new infection (44.4%, n = 4) and patients with complete remission (43.1%), lower among patients with partially same genotype (23.1%, n = 3) and new infection (22.6%, n = 2) and the lowest among patients with same genotype (6.2%, n = 1). Proportion of no pathology was the highest among patients with partially same genotype (23.1%, n = 1) and lower among patients with and new infections (16.1%, n = 5) and complete remission (12.7%). Proportion of no pathology was 0.0% in groups with same genotype and same/partially same genotype and new infection. In control group dependencies between age and category of HPV outcome after vaccination as well as between LEEP/surgery outcome and category of HPV outcome after vaccination were not confirmed (p > 0.05), Table 4 . Table 4 Dependencies between category of HPV outcomes after vaccination on age and LEEP/surgery outcome Characteristics Category of HPV outcomes after vaccination p Same genotype Partially same genotype Complete remission New infection Same/partially same genotype and new infection Gardasil group Age, years, n (%) < 25 3 (18.8) 2 (15.4) 11 (6.1) 2 (6.5) 2 (22.2) 0.674 < 35 8 (50.0) 9 (69.2) 112 (61.9) 16 (51.6) 4 (44.4) ≥ 35 5 (31.2) 2 (15.4) 58 (32.0) 13 (41.9) 3 (33.3) LEEP/surgery, n (%) LSIL 1 (6.2) 1 (7.7) 14 (7.7) 1 (3.2) 1 (11.1) 0.048 HSIL 1 (6.2) 3 (23.1) 78 (43.1) 7 (22.6) 4 (44.4) Adenocarcinoma/cancer 0 (0.0) 0 (0.0) 5 (2.8) 1 (3.2) 0 (0.0) No pathology 0 (0.0) 3 (23.1) 23 (12.7) 5 (16.1) 0 (0.0) No indication 14 (87.5) 6 (46.2) 61 (33.7) 17 (54.8) 4 (44.4) LEEP/surgery, n (%) Any outcome 2 (12.5) 7 (53.8) 120 (66.3) 14 (45.2) 5 (55.6) 0.041 No indication 14 (87.5) 6 (46.2) 61 (33.7) 17 (54.8) 4 (44.4) Control group Age, years, n (%) < 25 3 (13.0) 2 (33.3) 4 (12.5) 0 (0.0) 1 (20.0) 0.502 < 35 12 (52.2) 3 (50.0) 13 (40.6) 2 (50.0) 3 (60.0) ≥ 35 8 (34.8) 1 (16.7) 15 (46.9) 2 (50.0) 1 (20.0) LEEP/surgery, n (%) LSIL 0 (0.0) 0 (0.0) 1 (3.1) 0 (0.0) 0 (0.0) 0.144 HSIL 4 (17.4) 1 (16.7) 15 (46.9) 3 (75.0) 3 (60.0) Adenocarcinoma/cancer 0 (0.0) 0 (0.0) 0 (0.0) 1 (25.0) 0 (0.0) No pathology 1 (4.3) 2 (33.3) 4 (12.5) 0 (0.0) 0 (0.0) No indication 18 (78.3) 3 (50.0) 12 (37.5) 0 (0.0) 2 (40.0) LEEP/surgery, n (%) Any outcome 5 (21.7) 3 (50.0) 20 (62.5) 4 (100.0) 3 (60.0) 0.305 No indication 18 (78.3) 3 (50.0) 12 (37.5) 0 (0.0) 2 (40.0) n – number; LSIL — low-grade squamous intraepithelial lesion; HSIL — high-grade squamous intraepithelial lesion; LEEP- loop electrosurgical excision procedure; vac – vaccination. Groups compared with Fisher’s exact test. 4. Discussion The study was intended to answer the question about changes in the cervical smear for HPV in HPV-positive patients after receiving the 9-valent HPV vaccine. The main result of the analysis was that in the vaccinated group the rate of HPV disappearance was significantly higher over the follow-up period than in the control group. This applies especially to the so-called complete remission, i.e., the complete disappearance of the HPV virus - it was observed in nearly ¾ of vaccinated women (72.4%) compared to less than half of unvaccinated patients (45.7%). This effect is especially visible when analyzing the disappearance of HPV genotypes covered by the 9-valent vaccine. Proportion of positive HPV Gardasil genotype after vaccination/observation was significantly higher in group with positive HPV Gardasil genotype before vaccination/observation (51.9% vs 0.0%, p = 0.001). There are insufficient studies that could be related to our results. Just as the preventive effect of vaccination on the development of lesions has been proven, there are scientific reports showing the beneficial effect of vaccination on reducing the recurrence of HPV-related lesions. However, we have not been able to find any literature on the disappearance of HPV infection in the smear. Our previous analysis, including a smaller study group, showed the added value of vaccination in the group of HPV-positive patients [11]. Vaccination can reasonably be expected to prevent new HPV infections caused by different HPV types, as well as reinfections with the same HPV type. This protection applies to new exposures from infected partners and to autoinoculation from adjacent or distant sites that are already productively infected. Since the recurrence rate of HSIL after surgical treatment is still over 6%, it means that only eliminating or neutralizing the HPV virus gives a chance to reduce the percentage []. Persistent infection with a highly oncogenic HPV genotype is the only modifiable risk factor for pre- and cancer-related conditions. However, the mechanism of function of the HPV vaccine in patients already infected with HPV is still not fully understood. Konstantinos S Kechagias with co-authors presented systematic review and meta-analysis on the role of HPV vaccination at the time of local surgical treatment for cervical and other diseases related to HPV infection, with rigorous methodological assessment of risk of bias, heterogeneity, and appropriate data. The researchers revealed that the risk of recurrence of CIN2 + was reduced in vaccinated patients who were vaccinated compared with those who were not vaccinated (according to data collected from 11 articles). Interestingly, the effect estimate was stronger when the risk of recurrence of CIN2 + was assessed for disease related to HPV subtypes HPV16 or HPV18. The risk of recurrence of CIN3 was also reduced in vaccinated patients []. The authors' conclusions that the impact on reducing the recurrence of lesions associated with the presence of HPV 16 and 18 may be related to the fact that the availability of bivalent and quadrivalent vaccinations was the highest a few or a dozen years ago. Perhaps, thanks to the increasing availability of the 9-valent vaccine, in a dozen or so years we will be able to present a meta-analysis covering the disappearance of CIN 2 + lesions associated with other genotypes covered by the vaccine. In addition to the potential effect of HPV vaccination on reducing the risk of cervical recurrence, studies have shown a beneficial effect on HPV-dependent, non-oncogenic lesions, such as recurrent laryngeal papillomatosis or condyloma acuminata. Researchers also attempted to assess the impact of vaccination in other, less common HPV-related diseases, affecting the vulva or vagina. Testing for the presence of HPV DNA in a cervical smear is currently the only screening method allowing early detection of changes in the vagina or vulva. Evidence shows that prophylactic HPV vaccination, as in the case of cervical cancer precursors, also prevents HPV-related vulvar and vaginal HPV-associated precancers [9,10]. Several studies suggested that HPV vaccination has a statistically significant impact in reducing post-surgical recurrent disease both in women and men exposed to previous HPV infection [12, 13, 14]. In 2012, Joura et al. reported that HPV vaccination among women after surgical treatment for HPV-related disease significantly reduced the incidence of subsequent significant impact of adjuvant HPV vaccination in reducing the risk of recurrence of genital warts after initial surgical treatment [13]. In 2021, Ghelardi et al. documented the effectiveness of HPV vaccine in preventing recurrent disease after surgical treatment for vulvar high-grade squamous intraepithelial lesions [14]. There are discussions in extensive reviews about the reduced risk of recurrence of CIN lesions [15, 16] however, the time of administering the vaccine peri- or post-procedure has not been standardized and there are no clear guidelines on when it should be administered. A similar analysis was presented by the authors of the publication in 2023, in which they described the evidence for using prophylactic HPV vaccines in patients with HPV-associated disease before, during, or after treatment. The researchers discussed potential mechanisms by which individuals with HPV-associated disease may or may not benefit from prophylactic vaccines [17]. More and more doctors and scientific societies encourage the vaccination of an increasingly older patient population. The American Society for Colposcopy and Cervical Pathology recommends adherence to current CDC recommendations for vaccination of individuals aged 9 to 26 years and consideration of the possible benefit of adjuvant HPV vaccination during shared decision making for previously unvaccinated individuals aged 27 to 45 years who are undergoing treatment for CIN2+ [18]. Our previous work on the immune response confirms a higher titer of anti-HPV antibodies in post-vaccination patients who remain infected with HPV [19] but there are no scientific studies to date that describe the disappearance of infection in cervical smears. Our study group is under strict supervision, but observations made after more than a decade will certainly be interesting. The question remains whether in the future HPV- positive patients will experience a recurrence of SIL-type lesions in the cervix or lesions in the vagina and vulva. 5. Conclusions Vaccination against HPV significantly affects the disappearance of the viral infection in women not vaccinated during puberty. A statistically significant disappearance of HPV infection occurs in patients both diagnosed due to HPV and undergoing LEEP-conization due to HSIL. Vaccination of this group of women will probably reduce the occurrence of cervical, vaginal and vulvar intraepithelial neoplasia and other HPV-related lesions. Data is provided within the manuscript and the Supplementary information files. Declarations Author Contribution The authors declare no conflict of interests.Conceptualization, D.P.; Methodology, D.P.; Software, D.P. and S.M.-K.; Formal analysis, S.M.-K. and D.P.; Investigation, D.P. and S.M.-K.; Resources, D.P. and M.P.; Data curation, D.P. and S.M.-K.; Writing—original draft, D.P. and S.M.-K.; Writing—review and editing, D.P., S.M.-K. and R.J.; Visualization, S.M.-K.; Supervision, M.P. and R.J.; Project administration, D.P.; Funding acquisition, D.P. and M.P. All authors have read and agreed to the published version of the manuscript. Data Availability Data is provided within the manuscript and the Supplementary information files. References Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4. PMID: 38572751. Pan, J.; Kavanagh, K.; Cuschieri, K.; Pollock, K.G.; Gilbert, D.C.; Millan, D.; Bell, S.; Graham, S.V.; Williams, A.R.W.; Cruickshank, M.E.; et al. Increased risk of HPV-associated genital cancers in men and women as a consequence of pre-invasive disease. Int. J. Cancer 2019, 145, 427–434. Strander, B.; Hällgren, J.; Sparén, P. Effect of ageing on cervical or vaginal cancer in Swedish women previously treated for cervical intraepithelial neoplasia grade 3: Population based cohort study of long term incidence and mortality. BMJ 2014, 348, f7361. European Medicines Agency (EMA). Gardasil 9 Summary of Product Characteristics, https://www.ema.europa.eu/en/documents/product-information/gardasil-9-epar-product-information_en.pdf; 2020 [accessed September 9, 2020]. Merck Sharp & Dohme LLC, Rahway, NJ, USA. Gardasil®9 US Prescribing Information, https://www.merck.com/product/usa/pi_circulars/g/gardasil_9/gardasil_9_pi.pdf; 2023 [accessed 17 April 2023]. Preti, M., Rosso, S., Micheletti, L. et al. Risk of HPV-related extra-cervical cancers in women treated for cervical intraepithelial neoplasia. BMC Cancer 20 , 972 (2020). https://doi.org/10.1186/s12885-020-07452-6 Rene ́e M.F. Ebisch, Dominiek W.E. Rutten, Joanna IntHout, et al. Long-Lasting Increased Risk of Human Papillomavirus–Related Carcinomas and Premalignancies After Cervical Intraepithelial Neoplasia Grade 3: A Population-Based Cohort Study. J Clin Oncol, 35 (2017), pp. 2542-2550. DOI: https://doi.org/10.1200/JCO.2016. 71.4543 Kechagias KS, Kalliala I, Bowden SJ, Athanasiou A, Paraskevaidi M, Paraskevaidis E, Dillner J, Nieminen P, Strander B, Sasieni P, Veroniki AA, Kyrgiou M. Role of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: systematic review and meta-analysis. BMJ. 2022 Aug 3;378:e070135. doi: 10.1136/bmj-2022-070135. PMID: 35922074; PMCID: PMC9347010. Joura EA, Leodolter S, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, Garland SM, Harper DM, Tang GW, Ferris DG, Steben M, Jones RW, Bryan J, Taddeo FJ, Bautista OM, Esser MT, Sings HL, Nelson M, Boslego JW, Sattler C, Barr E, Paavonen J. Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials. Lancet. 2007 May 19;369(9574):1693-702. doi: 10.1016/S0140-6736(07)60777-6. PMID: 17512854. Dehlendorff C, Baandrup L, Kjaer SK. Real-World Effectiveness of Human Papillomavirus Vaccination Against Vulvovaginal High-Grade Precancerous Lesions and Cancers. J Natl Cancer Inst. 2021 Jul 1;113(7):869-874. doi: 10.1093/jnci/djaa209. PMID: 33377930; PMCID: PMC8246827. Pruski D, Millert-Kalińska S, Łagiedo M, Sikora J, Jach R, Przybylski M. Effect of HPV Vaccination on Virus Disappearance in Cervical Samples of a Cohort of HPV-Positive Polish Patients. J Clin Med. 2023 Dec 9;12(24):7592. doi: 10.3390/jcm12247592. PMID: 38137661; PMCID: PMC10743582. Joura, E.A.; Garland, S.M.; Paavonen, J.; Ferris, D.G.; Perez, G.; Ault, K.A.; Huh, W.K.; Sings, H.L.; James, M.W.; Haupt, R.M. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: Retrospective pooled analysis of trial data. BMJ 2012 , 344 , e1401. Coskuner, E.R.; Ozkan, T.A.; Karakose, A.; Dillioglugil, O.; Cevik, I. Impact of the quadrivalent HPV vaccine on disease recurrence in men exposed to HPV Infection: A randomized study. J. Sex. Med. 2014 , 11 , 2785–2791. Ghelardi A, Marrai R, Bogani G, Sopracordevole F, Bay P, Tonetti A, Lombardi S, Bertacca G, Joura EA. Surgical Treatment of Vulvar HSIL: Adjuvant HPV Vaccine Reduces Recurrent Disease. Vaccines (Basel). 2021 Jan 25;9(2):83. doi: 10.3390/vaccines9020083. PMID: 33503866; PMCID: PMC7911252. Eriksen DO, Jensen PT, Schroll JB, Hammer A. Human papillomavirus vaccination in women undergoing excisional treatment for cervical intraepithelial neoplasia and subsequent risk of recurrence: A systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2022 Jun;101(6):597-607. doi: 10.1111/aogs.14359. Epub 2022 Apr 26. PMID: 35470865; PMCID: PMC9564558. Di Donato V, Caruso G, Bogani G, Cavallari EN, Palaia G, Perniola G, Ralli M, Sorrenti S, Romeo U, Pernazza A, Pierangeli A, Clementi I, Mingoli A, Cassoni A, Tanzi F, Cuccu I, Recine N, Mancino P, de Vincentiis M, Valentini V, d'Ettorre G, Della Rocca C, Mastroianni CM, Antonelli G, Polimeni A, Muzii L, Palaia I. HPV Vaccination after Primary Treatment of HPV-Related Disease across Different Organ Sites: A Multidisciplinary Comprehensive Review and Meta-Analysis. Vaccines (Basel). 2022 Feb 4;10(2):239. doi: 10.3390/vaccines10020239. PMID: 35214697; PMCID: PMC8879645. Reuschenbach M, Doorbar J, Del Pino M, Joura EA, Walker C, Drury R, Rauscher A, Saah AJ. Prophylactic HPV vaccines in patients with HPV-associated diseases and cancer. Vaccine. 2023 Oct 6;41(42):6194-6205. doi: 10.1016/j.vaccine.2023.08.047. Epub 2023 Sep 12. PMID: 37704498. Sharpless KE, Marcus JZ, Kuroki LM, Wiser AL, Flowers L. ASCCP Committee Opinion: Adjuvant Human Papillomavirus Vaccine for Patients Undergoing Treatment for Cervical Intraepithelial Neoplasia. J Low Genit Tract Dis. 2023 Jan 1;27(1):93-96. doi: 10.1097/LGT.0000000000000703. Epub 2022 Oct 21. PMID: 36538783; PMCID: PMC9770105. Pruski D, Łagiedo-Żelazowska M, Millert-Kalińska S, Sikora J, Jach R, Przybylski M. Immunity after HPV Vaccination in Patients after Sexual Initiation. Vaccines (Basel). 2022 May 6;10(5):728. doi: 10.3390/vaccines10050728. PMID: 35632487; PMCID: PMC9144159. Additional Declarations No competing interests reported. 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Introduction","content":"\u003cp\u003eCervical cancer (CC) remains a significant global health challenge despite being theoretically preventable. It ranks as the fourth most common malignancy in women worldwide. In 2020 alone, there were an estimated 604,000 new cases and 342,000 deaths attributed to this disease [1]. An undeniable risk factor for cervical cancer and intraepithelial neoplasia is persistent infection with the human papillomavirus (HPV) \u0026ndash; not only genotypes 16 and 18, but also: 31, 45, 52. Infections with oncogenic HPV genotypes include not only lesions of the cervix, but also pre-cancerous conditions and cancers of the head and neck, vagina, vulva, anus, and penis. Detection and treatment of LSIL-CIN 1, HSIL-CIN 2 and CIN 3 lesions is now simple and widely available. The availability of numerous diagnostic tests, including the self-sampling option, and the low invasiveness of colposcopic examination mean that these tests are most often performed on an outpatient basis. The LEEP-conization procedure, which involves excising the lesion without or with the entire transformation zone, is a simple procedure that does not require the conditions of an operating room and can be performed by any trained gynecologist. Currently, a greater challenge is the diagnosis and treatment of HPV-related lesions including lesions in the vagina, vulva, and anus. Removal of this type of lesions is often not radical or impossible because the topography is too close to the bladder or rectum and carries a very high risk of damaging other organs and creating a fistula. The use of preventive vaccines in the population of sexually initiated women, including HPV-positive women, may facilitate remission of the HPV virus, create immunological immunity, and reduce the occurrence of SIL-type lesions, mainly in ​​the cervix, vagina, vulva, and anus.\u003c/p\u003e \u003cp\u003eDue to the discovery and implementation of preventive vaccinations against HPV, many countries are on the way to eliminating HPV-related cancers and diseases. Examples include New Zealand and Australia, Scandinavia, and Great Britain. In addition to population vaccination, these countries are also introducing solutions for the adult population - such as opportunistic HPV vaccination at universities.\u003c/p\u003e \u003cp\u003eIn fact, despite studies showing consistent results in the direction of efficacy, there is still skepticism in the scientific community about the use of the HPV vaccine as an adjuvant therapy, after local treatment, against relapses and in HPV-positive population after sexual initiation. Individuals with human papillomavirus (HPV)-related disease remain at risk for subsequent HPV infection and related disease after treatment of specific lesions. Additionally, patients treated for HPV-related high-grade histologic lesions have a significantly increased risk of developing HPV-related malignancies in the 20 years following treatment compared with the general population [2, 3]. More and more voices appear in the scientific and social debate, not only in the context of the preventive role of vaccination against HPV. The world is moving forward, now in the so-called \"post-HPV vaccination era\" - this is the time when the first patients vaccinated prophylactically at the age of 14 reached the common age for the development of CIN - studies and meta-analyses show what the risk is for these patients in terms of the development of HPV-dependent lesions. There are no documented contraindications to vaccination against HPV in people with current HPV infection [4, 5]. Additionally, people with previously diagnosed HPV infection have an increased risk of recurrence of HPV-related lesions, even after surgical treatment [6, 7, 8]. What is more, not only children and young adults decide to get vaccinated - but also adult women and men. This is a dimension of mutual responsibility between couples. Evidence also shows the value of vaccinating people who are immunosuppressed and infected with human immunodeficiency virus (HIV). People with warts and condylomas developing because of infection with non-oncogenic HPV types are vaccinated - although there is no hard evidence to reduce the risk of recurrence [9, 10].\u003c/p\u003e \u003cp\u003eChanges in sexual customs and behavior in both women and men may in the coming decades influence the epidemiology of HPV-related cancers and diseases occurring in the nasopharynx, larynx, vagina, vulva, cervix, and anus. In these population groups, the vaccine may be the only effective mean of prevention. It is worth mentioning how difficult it is to obtain an appropriate amount of material for molecular tests and how difficult it is to detect and recognize pre-cancerous lesions of the SIL type that do not occur in the cervix. Secondary prevention tools beyond the cervix are non-existent. Since strictly therapeutic vaccines are still in the research phase and are not commercially available, many adults infected with HPV have undergone vaccination against HPV. It should be emphasized that the use of the vaccine should be an additional measure and therapeutic procedures cannot be abandoned in justified cases, such as HSIL changes. However, the population of people willing to vaccinate in adulthood is constantly increasing thanks to growing public awareness. In recent years, reports have begun to appear regarding the beneficial effect of vaccination, the possibility of reducing the risk of recurrence of lesions, and the potential impact on the disappearance of HPV. This study aims to show the results and changes in the smear for HPV DNA in patients after receiving a vaccination course with a 9-valent HPV vaccine in women with HPV infection diagnosed in a cervical smear and this is an extended study of work published last year.\u003c/p\u003e"},{"header":"2. Methodology","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Study design\u003c/h2\u003e \u003cp\u003eWe provide a prospective, ongoing, non-randomized study to provide the effect of nine-valent HPV vaccination in HPV-positive patients with Gardasil\u0026reg;9 recombinant, nine-valent vaccine. This study was performed in line with the principles of the Declaration of Helsinki. The Bioethical Committee approved the study protocol (95/2021). We obtained written consent for the study from all patients.\u003c/p\u003e \u003cp\u003eAll subjects reported to a private gynecological practice focused and specialized in cervical cancer diagnosis in the years 2020\u0026ndash;2023. This is a group of patients who called for in-depth diagnostics due to a positive HPV HR test result and/or an abnormal cytological result. To verify the final diagnosis, the patients underwent colposcopy with cervical biopsy and curettage of the cervical canal. To enhance the immunological response, all subjects were offered vaccination against HPV with the nine-valent vaccine in the 0-2-6 scheme. Out of 320 patients, 250 (78.1%) decided to be vaccinated and 70 (21.9%) did not.\u003c/p\u003e \u003cp\u003eThe inclusion criteria comprised:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eAdult females only.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eNon-pregnant or postpartum individuals.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eSubjects not undergoing immunosuppressive drug treatment.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eNo prior vaccination with other HPV vaccines.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eExpressing informed written consent to participate.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eConsenting to proposed surgical diagnostics and potential surgical excision treatment if indicated.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eHaving received three doses of the nine-valent HPV vaccination following the 0- 2- 6 month schedule.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe exclusion criteria were as follows:\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e1. Refusal of potential treatment for squamous intraepithelial lesions.\u003c/h3\u003e\n\n\u003ch3\u003e2. Failure to complete the full vaccination regimen.\u003c/h3\u003e\n\u003cp\u003eThe analysis is the last chance to assess the effect of adjuvant anti-HPV vaccination in the population not vaccinated in adolescence, because a generation that was more likely to be covered by primary prevention programs is entering adulthood.\u003c/p\u003e \u003cp\u003eAll patients with histopathologically confirmed high-grade squamous intraepithelial lesions (CIN 2+) were treated according to the current recommendations of the Polish Colposcopic Society, with the loop electrosurgical excision procedure (LEEP), and then subjected to strict control every six months. The control group includes seventy HPV-positive patients diagnosed with pre-neoplastic lesions who decided not to receive the HPV vaccine.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.2. LBC, HPV genotyping and colposcopy with punch biopsy\u003c/h2\u003e \u003cp\u003eThe cervix and endocervix material were collected with a Cyto-Brush and placed in a liquid medium PreservCyt\u0026reg; (Roche Diagnostic Systems, Meylan, France).\u003c/p\u003e \u003cp\u003eThen, we performed PCR followed by a DNA enzyme immunoassay with a reverse hybridization line probe assay for HPV detection. To characterize HPV-positive samples, sequence analysis was performed. We used Roche Linear Array HPV Genotyping Test\u0026reg;, which identifies 32 HPV DNA of the following genotypes: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 (high-risk genotypes); 26, 53, 66, 70, 73 and 82 (probable high-risk genotypes); and 6, 11, 40, 42, 43, 44, 54, 61, 62, 67, 81, 83 and 89 (low-risk genotypes) or the BD Onclarity HPV Assay detecting 14 different HPV genotypes while incorporating a β-globininternal control (IC) as a processing control. The HPV genotypes that can be detected individually are HPV 16, 18, 31, 45, 51, and 52. The remaining genotypes are grouped as follows: HPV 33/58, 56/59/66, and 35/39/68. The IC serves as a control to ensure the accuracy and validity of the assay.\u003c/p\u003e \u003cp\u003eColposcopy was performed in case of: (1) abnormal cervical image under gynecological examination; (2) abnormal LBC result, i.e., ASC-US, AGC, LSIL, ASC-H, HSIL, cervical cancer; and (3) positive high-risk HPV test result (genotype 16, 18 or 31). The colposcopy was performed according to the International Federation of Cervical Pathology and Colposcopy classification. In all cases, at least one cervix biopsy from transformation zone (TZ) and cervical canal curettage was taken.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Statistical analysis\u003c/h2\u003e \u003cp\u003eAnalysis was conducted with statistical software R, version R4.1.2. All analyses assumed significance level of α\u0026thinsp;=\u0026thinsp;0.05. Nominal variables were presented as n and %, age was summarised with mean and standard deviation. Dependencies between categorical variables were analysed with Pearson\u0026rsquo;s Chi-square test or Fisher\u0026rsquo;s exact test, as appropriate. Comparison of age as numeric variable between study groups was conducted with t-Student test. Normality of distributions was assessed with Shapiro-Wilk test, skewness and kurtosis. Variance homogeneity was assessed with Levene\u0026rsquo;s test.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Study groups characteristics and comparison\u003c/h2\u003e \u003cp\u003eStudy groups characteristics were presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Patients from both study groups did not differ in age, cytology outcome, HPV genotypes before vaccination, biopsy outcome, and LEEP/surgery outcome (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). HPV outcomes after vaccination differentiated the groups. Vaccinated group had significantly lower proportion of positive outcome for any HPV genotype (27.6% vs 54.3% in control group), p\u0026thinsp;\u0026lt;\u0026thinsp;0.001. Vaccinated group had significantly lower proportion of positive outcome for HPV Gardasil genotype (14.8% vs 40.0% in control group), p\u0026thinsp;\u0026lt;\u0026thinsp;0.001. Vaccination/observation outcome described by 5-category scale was significantly different between groups, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001. Proportion of patients with same genotypes after vaccination was lower in Vaccinated group (6.4% vs 32.9% in control group). Proportion of patients with partially same genotypes after vaccination was lower in Vaccinated group (5.2% vs 8.6%). Complete remission rate was higher in Vaccinated group (72.4% vs 45.7%). Proportion of new infections was higher in Vaccinated group (12.4% vs 5.7%) and proportion of patients with same/partially same genotype and new infection was higher in Vaccinated group (3.6% vs 7.1% in control group).\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 and comparison of study groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVaccinated\u003c/p\u003e \u003cp\u003egroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMD (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e250 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e70 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32.72\u0026thinsp;\u0026plusmn;\u0026thinsp;6.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32.50\u0026thinsp;\u0026plusmn;\u0026thinsp;6.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.22 (-1.55;2.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.803\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.110\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e149 (59.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33 (47.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e81 (32.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27 (38.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCytology, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNILM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40 (16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"6\" rowspan=\"7\"\u003e \u003cp\u003e0.831\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAS-CUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e33 (13.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (20.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e88 (35.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25 (35.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASC-H\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e47 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (15.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34 (13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (10.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAGC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHPV Gardasil genotype, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e207 (82.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e54 (77.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.366\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43 (17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16 (22.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHPV genotype, n (%)*\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23 (9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.054\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.590\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e109 (43.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e37 (52.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.215\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e37 (14.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.071\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40 (16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.871\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.354\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.537\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.318\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23 (9.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19 (7.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.987\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.621\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.416\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.370\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.741\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.082\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.475\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.180\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.697\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.615\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.524\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCP6108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCP6109\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.590\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eP3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiopsy, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e57 (22.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e0.669\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e115 (46.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32 (45.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenocarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo pathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e55 (22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21 (30.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo indication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (7.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLEEP/surgery, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.325\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e93 (37.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26 (37.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenocarcinoma/cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo pathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31 (12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (10.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo indication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e102 (40.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLEEP/surgery, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e148 (59.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.216\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo indication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e102 (40.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35 (50.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHPV any genotype, after vac., n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e69 (27.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e38 (54.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e181 (72.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32 (45.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHPV Gardasil genotype, after vac., n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e37 (14.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e213 (85.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42 (60.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCategory (before vs after vac.), n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSame genotype\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23 (32.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePartially same genotype\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (8.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplete remission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e181 (72.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32 (45.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNew infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31 (12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (5.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSame/partially same genotype and new infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (7.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSD \u0026ndash; standard deviation, MD \u0026ndash; mean difference (Gardasil group vs control group), n -number, CI \u0026ndash; confidence interval; ASC-US \u0026mdash; atypical squamous cells of undetermined significance; AGC \u0026mdash; atypical glandular cells; ASC-H \u0026mdash; atypical squamous cells, cannot exclude a high-grade squamous intraepithelial lesion; LSIL \u0026mdash; low-grade squamous intraepithelial lesion; HSIL \u0026mdash; high-grade squamous intraepithelial lesion; HPV \u0026mdash; human papillomavirus; NILM \u0026mdash; negative for intraepithelial lesion or malignancy; LBC \u0026mdash;liquid-based cytology; P1 - HPV 33/58; P2 \u0026ndash; HPV 56/59/66; P3\u0026ndash;35/39/68; LEEP- loop electrosurgical excision procedure; vac \u0026ndash; vaccination. Groups compared with t-Student test\u003csup\u003e1\u003c/sup\u003e, Pearson\u0026rsquo;s Chi-square test\u003csup\u003e2\u003c/sup\u003e or Fisher\u0026rsquo;s exact test, as appropriate.\u003c/p\u003e \u003cp\u003e* Various genotypes could be observed for one patient.\u003c/p\u003e \u003cp\u003e \u003cb\u003e3.2. Dependencies between age and HPV +/- after vaccination as well as between LEEP/surgery outcome and HPV +/- after vaccination\u003c/b\u003e \u003c/p\u003e \u003cp\u003eIn Vaccinated group HPV outcome after vaccination was significantly dependant on LEEP/surgery outcome. Proportion of no indication to LEEP/surgery was significantly higher among patients with positive HPV after vaccination compared to negative HPV after vaccination (59.4% vs 33.7%), p\u0026thinsp;\u0026lt;\u0026thinsp;0.001. Structure of LEEP/surgery detailed outcome was significantly different between positive and negative HPV after surgery, p\u0026thinsp;=\u0026thinsp;0.005, with main difference lying in proportion of HSIL, which was lower among patients with positive HPV outcome (21.7% vs 43.1% among patients with negative HPV outcome after vaccination). Dependence of age and HPV outcome after vaccination was not confirmed (p\u0026thinsp;=\u0026thinsp;0.163).\u003c/p\u003e \u003cp\u003eIn control group dependencies between age and HPV outcome after vaccination as well as between LEEP/surgery outcome and HPV outcome after vaccination were not confirmed (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\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\u003eDependencies between HPV outcome after vaccination and age and between HPV outcome after vaccination and LEEP/surgery outcome\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eVaccinated group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eHPV any genotype after vac.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHPV any genotype after vac.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.163\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6 (15.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.424\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e37 (53.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e112 (61.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e20 (52.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e13 (40.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e58 (32.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12 (31.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e15 (46.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLEEP/surgery, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.161\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (21.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e78 (43.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11 (28.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e15 (46.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenocarcinoma/cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo pathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3 (7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4 (12.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo indication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e41 (59.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61 (33.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e23 (60.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e12 (37.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLEEP/surgery, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28 (40.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e120 (66.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e15 (39.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e20 (62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.093\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo indication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e41 (59.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61 (33.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e23 (60.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e12 (37.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eGroups compared with Pearson\u0026rsquo;s Chi-square test or Fisher\u0026rsquo;s exact test\u003csup\u003e1\u003c/sup\u003e, as appropriate.\u003c/p\u003e \u003cp\u003en \u0026ndash; number; LSIL \u0026mdash; low-grade squamous intraepithelial lesion; HSIL \u0026mdash; high-grade squamous intraepithelial lesion; LEEP- loop electrosurgical excision procedure; vac \u0026ndash; vaccination.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Dependencies between HPV (Gardasil type) +/- before vaccination and HPV +/- after vaccination\u003c/h2\u003e \u003cp\u003eIn Gardasil group proportion of positive HPV outcomes after vaccination did not depend on proportion of positive outcomes of HPV Gardasil genotype before vaccination, both in perspective of any HPV genotype after vaccination and Gardasil HPV genotype after vaccination (p\u0026thinsp;=\u0026thinsp;0.890 and p\u0026thinsp;=\u0026thinsp;0.176, respectively).\u003c/p\u003e \u003cp\u003eIn control group no difference between groups with and without HPV Gardasil genotype before vaccination/observation was observed in proportion of positive HPV of any genotype after vaccination/observation (p\u0026thinsp;=\u0026thinsp;0.069). Proportion of positive HPV Gardasil genotype after vaccination/observation was higher in group with positive HPV Gardasil genotype before vaccination/observation (51.9% vs 0.0% in group without HPV Gardasil genotype before vaccination/observation), p\u0026thinsp;=\u0026thinsp;0.001, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDependence between HPV outcomes before vaccination (Gardasil genotype) and HPV outcomes after vaccination\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eVaccinated group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eHPV Gardasil genotype before vac.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHPV Gardasil genotype before vac.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHPV any genotype, after vac., n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e58 (28.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (25.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.890\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e33 (61.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5 (31.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.069\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e149 (72.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e32 (74.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e21 (38.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e11 (68.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHPV Gardasil genotype, after vac., n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34 (91.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e173 (81.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.176\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e28 (51.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e26 (48.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e16 (100.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eHPV \u0026mdash; human papillomavirus; vac \u0026ndash; vaccination.\u003c/p\u003e \u003cp\u003eGroups compared with Pearson\u0026rsquo;s Chi-square test.\u003c/p\u003e \u003cp\u003e \u003cb\u003eDependencies between age and category as well as between LEEP/surgery outcome and category\u003c/b\u003e \u003c/p\u003e \u003cp\u003eIn Gardasil group category of HPV outcome after vaccination was significantly related to LEEP/surgery outcome. Proportion of no indication to LEEP/surgery was the highest among patients with same genotype after vaccination (87.5%), lower among patients with new infection (54.8%), partially same genotype (46.2%, n\u0026thinsp;=\u0026thinsp;6) and same/partially same genotype with new infections (44.4%, n\u0026thinsp;=\u0026thinsp;4). Proportion of no indication was the lowest among patients with complete remission (33.7%), p\u0026thinsp;=\u0026thinsp;0.041.\u003c/p\u003e \u003cp\u003eDetailed LEEP/surgery outcome was significantly related to category of HPV outcome after vaccination, p\u0026thinsp;=\u0026thinsp;0.048. Main differences were observed in proportion of HSIL and proportion of no pathology. Proportion of HSIL was the highest among patients with same/partially same genotype and new infection (44.4%, n\u0026thinsp;=\u0026thinsp;4) and patients with complete remission (43.1%), lower among patients with partially same genotype (23.1%, n\u0026thinsp;=\u0026thinsp;3) and new infection (22.6%, n\u0026thinsp;=\u0026thinsp;2) and the lowest among patients with same genotype (6.2%, n\u0026thinsp;=\u0026thinsp;1). Proportion of no pathology was the highest among patients with partially same genotype (23.1%, n\u0026thinsp;=\u0026thinsp;1) and lower among patients with and new infections (16.1%, n\u0026thinsp;=\u0026thinsp;5) and complete remission (12.7%). Proportion of no pathology was 0.0% in groups with same genotype and same/partially same genotype and new infection.\u003c/p\u003e \u003cp\u003eIn control group dependencies between age and category of HPV outcome after vaccination as well as between LEEP/surgery outcome and category of HPV outcome after vaccination were not confirmed (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDependencies between category of HPV outcomes after vaccination on age and LEEP/surgery outcome\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eCategory of HPV outcomes after vaccination\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSame genotype\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePartially same genotype\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eComplete remission\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNew infection\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSame/partially same genotype and new infection\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGardasil group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2 (22.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.674\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (69.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e112 (61.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e16 (51.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4 (44.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (31.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e58 (32.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13 (41.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLEEP/surgery, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14 (7.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.048\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (23.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e78 (43.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7 (22.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4 (44.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenocarcinoma/cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo pathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (23.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5 (16.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo indication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (87.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e61 (33.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e17 (54.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4 (44.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLEEP/surgery, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (53.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e120 (66.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e14 (45.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5 (55.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo indication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (87.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (46.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e61 (33.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e17 (54.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4 (44.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eControl group\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.502\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (52.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13 (40.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3 (60.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (34.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15 (46.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1 (20.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLEEP/surgery, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.144\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (17.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15 (46.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3 (75.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3 (60.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdenocarcinoma/cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo pathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo indication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18 (78.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2 (40.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLEEP/surgery, n (%)\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\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (21.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20 (62.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.305\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo indication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18 (78.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2 (40.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003en \u0026ndash; number; LSIL \u0026mdash; low-grade squamous intraepithelial lesion; HSIL \u0026mdash; high-grade squamous intraepithelial lesion; LEEP- loop electrosurgical excision procedure; vac \u0026ndash; vaccination.\u003c/p\u003e \u003cp\u003eGroups compared with Fisher\u0026rsquo;s exact test.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe study was intended to answer the question about changes in the cervical smear for HPV in HPV-positive patients after receiving the 9-valent HPV vaccine. The main result of the analysis was that in the vaccinated group the rate of HPV disappearance was significantly higher over the follow-up period than in the control group. This applies especially to the so-called complete remission, i.e., the complete disappearance of the HPV virus - it was observed in nearly \u0026frac34; of vaccinated women (72.4%) compared to less than half of unvaccinated patients (45.7%). This effect is especially visible when analyzing the disappearance of HPV genotypes covered by the 9-valent vaccine. Proportion of positive HPV Gardasil genotype after vaccination/observation was significantly higher in group with positive HPV Gardasil genotype before vaccination/observation (51.9% vs 0.0%, p\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eThere are insufficient studies that could be related to our results. Just as the preventive effect of vaccination on the development of lesions has been proven, there are scientific reports showing the beneficial effect of vaccination on reducing the recurrence of HPV-related lesions. However, we have not been able to find any literature on the disappearance of HPV infection in the smear. Our previous analysis, including a smaller study group, showed the added value of vaccination in the group of HPV-positive patients [11].\u003c/p\u003e \u003cp\u003eVaccination can reasonably be expected to prevent new HPV infections caused by different HPV types, as well as reinfections with the same HPV type. This protection applies to new exposures from infected partners and to autoinoculation from adjacent or distant sites that are already productively infected. Since the recurrence rate of HSIL after surgical treatment is still over 6%, it means that only eliminating or neutralizing the HPV virus gives a chance to reduce the percentage []. Persistent infection with a highly oncogenic HPV genotype is the only modifiable risk factor for pre- and cancer-related conditions. However, the mechanism of function of the HPV vaccine in patients already infected with HPV is still not fully understood.\u003c/p\u003e \u003cp\u003e Konstantinos S Kechagias with co-authors presented systematic review and meta-analysis on the role of HPV vaccination at the time of local surgical treatment for cervical and other diseases related to HPV infection, with rigorous methodological assessment of risk of bias, heterogeneity, and appropriate data. The researchers revealed that the risk of recurrence of CIN2\u0026thinsp;+\u0026thinsp;was reduced in vaccinated patients who were vaccinated compared with those who were not vaccinated (according to data collected from 11 articles). Interestingly, the effect estimate was stronger when the risk of recurrence of CIN2\u0026thinsp;+\u0026thinsp;was assessed for disease related to HPV subtypes HPV16 or HPV18. The risk of recurrence of CIN3 was also reduced in vaccinated patients []. The authors' conclusions that the impact on reducing the recurrence of lesions associated with the presence of HPV 16 and 18 may be related to the fact that the availability of bivalent and quadrivalent vaccinations was the highest a few or a dozen years ago. Perhaps, thanks to the increasing availability of the 9-valent vaccine, in a dozen or so years we will be able to present a meta-analysis covering the disappearance of CIN 2\u0026thinsp;+\u0026thinsp;lesions associated with other genotypes covered by the vaccine.\u003c/p\u003e \u003cp\u003eIn addition to the potential effect of HPV vaccination on reducing the risk of cervical recurrence, studies have shown a beneficial effect on HPV-dependent, non-oncogenic lesions, such as recurrent laryngeal papillomatosis or condyloma acuminata. Researchers also attempted to assess the impact of vaccination in other, less common HPV-related diseases, affecting the vulva or vagina. Testing for the presence of HPV DNA in a cervical smear is currently the only screening method allowing early detection of changes in the vagina or vulva. Evidence shows that prophylactic HPV vaccination, as in the case of cervical cancer precursors, also prevents HPV-related vulvar and vaginal HPV-associated precancers [9,10].\u003c/p\u003e \u003cp\u003eSeveral studies suggested that HPV vaccination has a statistically significant impact in reducing post-surgical recurrent disease both in women and men exposed to previous HPV infection [12, 13, 14]. In 2012, Joura et al. reported that HPV vaccination among women after surgical treatment for HPV-related disease significantly reduced the incidence of subsequent significant impact of adjuvant HPV vaccination in reducing the risk of recurrence of genital warts after initial surgical treatment [13]. In 2021, Ghelardi et al. documented the effectiveness of HPV vaccine in preventing recurrent disease after surgical treatment for vulvar high-grade squamous intraepithelial lesions [14]. There are discussions in extensive reviews about the reduced risk of recurrence of CIN lesions [15, 16] however, the time of administering the vaccine peri- or post-procedure has not been standardized and there are no clear guidelines on when it should be administered.\u003c/p\u003e \u003cp\u003eA similar analysis was presented by the authors of the publication in 2023, in which they described the evidence for using prophylactic HPV vaccines in patients with HPV-associated disease before, during, or after treatment. The researchers discussed potential mechanisms by which individuals with HPV-associated disease may or may not benefit from prophylactic vaccines [17].\u003c/p\u003e \u003cp\u003eMore and more doctors and scientific societies encourage the vaccination of an increasingly older patient population. The American Society for Colposcopy and Cervical Pathology recommends adherence to current CDC recommendations for vaccination of individuals aged 9 to 26 years and consideration of the possible benefit of adjuvant HPV vaccination during shared decision making for previously unvaccinated individuals aged 27 to 45 years who are undergoing treatment for CIN2+ [18].\u003c/p\u003e \u003cp\u003eOur previous work on the immune response confirms a higher titer of anti-HPV antibodies in post-vaccination patients who remain infected with HPV [19] but there are no scientific studies to date that describe the disappearance of infection in cervical smears.\u003c/p\u003e \u003cp\u003eOur study group is under strict supervision, but observations made after more than a decade will certainly be interesting. The question remains whether in the future HPV- positive patients will experience a recurrence of SIL-type lesions in the cervix or lesions in the vagina and vulva.\u003c/p\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eVaccination against HPV significantly affects the disappearance of the viral infection in women not vaccinated during puberty. A statistically significant disappearance of HPV infection occurs in patients both diagnosed due to HPV and undergoing LEEP-conization due to HSIL. Vaccination of this group of women will probably reduce the occurrence of cervical, vaginal and vulvar intraepithelial neoplasia and other HPV-related lesions.\u003c/p\u003e \u003cp\u003e Data is provided within the manuscript and the Supplementary information files.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eThe authors declare no conflict of interests.Conceptualization, D.P.; Methodology, D.P.; Software, D.P. and S.M.-K.; Formal analysis, S.M.-K. and D.P.; Investigation, D.P. and S.M.-K.; Resources, D.P. and M.P.; Data curation, D.P. and S.M.-K.; Writing\u0026mdash;original draft, D.P. and S.M.-K.; Writing\u0026mdash;review and editing, D.P., S.M.-K. and R.J.; Visualization, S.M.-K.; Supervision, M.P. and R.J.; Project administration, D.P.; Funding acquisition, D.P. and M.P. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData is provided within the manuscript and the Supplementary information files.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4. PMID: 38572751.\u003c/li\u003e\n\u003cli\u003ePan, J.; Kavanagh, K.; Cuschieri, K.; Pollock, K.G.; Gilbert, D.C.; Millan, D.; Bell, S.; Graham, S.V.; Williams, A.R.W.; Cruickshank, M.E.; et al. Increased risk of HPV-associated genital cancers in men and women as a consequence of pre-invasive disease. Int. J. Cancer 2019, 145, 427\u0026ndash;434.\u003c/li\u003e\n\u003cli\u003eStrander, B.; H\u0026auml;llgren, J.; Spar\u0026eacute;n, P. Effect of ageing on cervical or vaginal cancer in Swedish women previously treated for cervical intraepithelial neoplasia grade 3: Population based cohort study of long term incidence and mortality. BMJ 2014, 348, f7361.\u003c/li\u003e\n\u003cli\u003eEuropean Medicines Agency (EMA). Gardasil 9 Summary of Product Characteristics, https://www.ema.europa.eu/en/documents/product-information/gardasil-9-epar-product-information_en.pdf; 2020 [accessed September 9, 2020].\u003c/li\u003e\n\u003cli\u003eMerck Sharp \u0026amp; Dohme LLC, Rahway, NJ, USA. Gardasil\u0026reg;9 US Prescribing Information, https://www.merck.com/product/usa/pi_circulars/g/gardasil_9/gardasil_9_pi.pdf; 2023 [accessed 17 April 2023].\u003c/li\u003e\n\u003cli\u003ePreti, M., Rosso, S., Micheletti, L. \u003cem\u003eet al.\u003c/em\u003e Risk of HPV-related extra-cervical cancers in women treated for cervical intraepithelial neoplasia. \u003cem\u003eBMC Cancer\u003c/em\u003e\u003cstrong\u003e20\u003c/strong\u003e, 972 (2020). https://doi.org/10.1186/s12885-020-07452-6\u003c/li\u003e\n\u003cli\u003eRene ́e M.F. Ebisch, Dominiek W.E. Rutten, Joanna IntHout, et al. Long-Lasting Increased Risk of Human Papillomavirus\u0026ndash;Related Carcinomas and Premalignancies After Cervical Intraepithelial Neoplasia Grade 3: A Population-Based Cohort Study. J Clin Oncol, 35 (2017), pp. 2542-2550. DOI: https://doi.org/10.1200/JCO.2016. 71.4543 \u003c/li\u003e\n\u003cli\u003eKechagias KS, Kalliala I, Bowden SJ, Athanasiou A, Paraskevaidi M, Paraskevaidis E, Dillner J, Nieminen P, Strander B, Sasieni P, Veroniki AA, Kyrgiou M. Role of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: systematic review and meta-analysis. BMJ. 2022 Aug 3;378:e070135. doi: 10.1136/bmj-2022-070135. PMID: 35922074; PMCID: PMC9347010.\u003c/li\u003e\n\u003cli\u003eJoura EA, Leodolter S, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, Garland SM, Harper DM, Tang GW, Ferris DG, Steben M, Jones RW, Bryan J, Taddeo FJ, Bautista OM, Esser MT, Sings HL, Nelson M, Boslego JW, Sattler C, Barr E, Paavonen J. Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials. Lancet. 2007 May 19;369(9574):1693-702. doi: 10.1016/S0140-6736(07)60777-6. PMID: 17512854.\u003c/li\u003e\n\u003cli\u003eDehlendorff C, Baandrup L, Kjaer SK. Real-World Effectiveness of Human Papillomavirus Vaccination Against Vulvovaginal High-Grade Precancerous Lesions and Cancers. J Natl Cancer Inst. 2021 Jul 1;113(7):869-874. doi: 10.1093/jnci/djaa209. PMID: 33377930; PMCID: PMC8246827.\u003c/li\u003e\n\u003cli\u003ePruski D, Millert-Kalińska S, Łagiedo M, Sikora J, Jach R, Przybylski M. Effect of HPV Vaccination on Virus Disappearance in Cervical Samples of a Cohort of HPV-Positive Polish Patients. J Clin Med. 2023 Dec 9;12(24):7592. doi: 10.3390/jcm12247592. PMID: 38137661; PMCID: PMC10743582.\u003c/li\u003e\n\u003cli\u003eJoura, E.A.; Garland, S.M.; Paavonen, J.; Ferris, D.G.; Perez, G.; Ault, K.A.; Huh, W.K.; Sings, H.L.; James, M.W.; Haupt, R.M. Effect of the human papillomavirus (HPV) quadrivalent vaccine in a subgroup of women with cervical and vulvar disease: Retrospective pooled analysis of trial data. \u003cem\u003eBMJ\u003c/em\u003e\u003cstrong\u003e2012\u003c/strong\u003e, \u003cem\u003e344\u003c/em\u003e, e1401. \u003c/li\u003e\n\u003cli\u003eCoskuner, E.R.; Ozkan, T.A.; Karakose, A.; Dillioglugil, O.; Cevik, I. Impact of the quadrivalent HPV vaccine on disease recurrence in men exposed to HPV Infection: A randomized study. \u003cem\u003eJ. Sex. Med.\u003c/em\u003e\u003cstrong\u003e2014\u003c/strong\u003e, \u003cem\u003e11\u003c/em\u003e, 2785\u0026ndash;2791. \u003c/li\u003e\n\u003cli\u003eGhelardi A, Marrai R, Bogani G, Sopracordevole F, Bay P, Tonetti A, Lombardi S, Bertacca G, Joura EA. Surgical Treatment of Vulvar HSIL: Adjuvant HPV Vaccine Reduces Recurrent Disease. Vaccines (Basel). 2021 Jan 25;9(2):83. doi: 10.3390/vaccines9020083. PMID: 33503866; PMCID: PMC7911252.\u003c/li\u003e\n\u003cli\u003eEriksen DO, Jensen PT, Schroll JB, Hammer A. Human papillomavirus vaccination in women undergoing excisional treatment for cervical intraepithelial neoplasia and subsequent risk of recurrence: A systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2022 Jun;101(6):597-607. doi: 10.1111/aogs.14359. Epub 2022 Apr 26. PMID: 35470865; PMCID: PMC9564558.\u003c/li\u003e\n\u003cli\u003eDi Donato V, Caruso G, Bogani G, Cavallari EN, Palaia G, Perniola G, Ralli M, Sorrenti S, Romeo U, Pernazza A, Pierangeli A, Clementi I, Mingoli A, Cassoni A, Tanzi F, Cuccu I, Recine N, Mancino P, de Vincentiis M, Valentini V, d\u0026apos;Ettorre G, Della Rocca C, Mastroianni CM, Antonelli G, Polimeni A, Muzii L, Palaia I. HPV Vaccination after Primary Treatment of HPV-Related Disease across Different Organ Sites: A Multidisciplinary Comprehensive Review and Meta-Analysis. Vaccines (Basel). 2022 Feb 4;10(2):239. doi: 10.3390/vaccines10020239. PMID: 35214697; PMCID: PMC8879645.\u003c/li\u003e\n\u003cli\u003eReuschenbach M, Doorbar J, Del Pino M, Joura EA, Walker C, Drury R, Rauscher A, Saah AJ. Prophylactic HPV vaccines in patients with HPV-associated diseases and cancer. Vaccine. 2023 Oct 6;41(42):6194-6205. doi: 10.1016/j.vaccine.2023.08.047. Epub 2023 Sep 12. PMID: 37704498.\u003c/li\u003e\n\u003cli\u003eSharpless KE, Marcus JZ, Kuroki LM, Wiser AL, Flowers L. ASCCP Committee Opinion: Adjuvant Human Papillomavirus Vaccine for Patients Undergoing Treatment for Cervical Intraepithelial Neoplasia. J Low Genit Tract Dis. 2023 Jan 1;27(1):93-96. doi: 10.1097/LGT.0000000000000703. Epub 2022 Oct 21. PMID: 36538783; PMCID: PMC9770105.\u003c/li\u003e\n\u003cli\u003ePruski D, Łagiedo-Żelazowska M, Millert-Kalińska S, Sikora J, Jach R, Przybylski M. Immunity after HPV Vaccination in Patients after Sexual Initiation. Vaccines (Basel). 2022 May 6;10(5):728. doi: 10.3390/vaccines10050728. PMID: 35632487; PMCID: PMC9144159.\u003c/li\u003e\n\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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"HPV vaccination, 9-valent vaccination, HPV infection, treatment of HPV, HPV-related disease, SIL","lastPublishedDoi":"10.21203/rs.3.rs-4594994/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4594994/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAn undeniable risk factor for cervical cancer and intraepithelial neoplasia is persistent infection with HPV \u0026ndash; types: 16,18, 31, 45, 52 and others. Changes in sexual behavior may in the coming decades influence the epidemiology of HPV-related lesions. For those diseases, vaccination against HPV may be the only effective mean of prevention. Our study aims to show the results and changes in the smear for HPV DNA in patients after receiving a vaccination course with a 9-valent HPV vaccine in women with HPV infection. Out of 320 subjects, with HPV- positive result 250 (78.1%) decided to be vaccinated against HPV and 70 (21.9%) did not. In the vaccinated group the rate of HPV disappearance was significantly higher over the follow-up period than in the control group. This applies especially to the complete disappearance of the HPV - in 72.4% vaccinated women compared to 45.7% unvaccinated. This effect is especially visible when analyzing the disappearance of HPV genotypes covered by the 9-valent vaccine. A significant disappearance of HPV infection occurs in patients both diagnosed due to HPV and undergoing LEEP-conization due to HSIL. Vaccination of this group of women will probably reduce the occurrence of different HPV-related lesions.\u003c/p\u003e","manuscriptTitle":"Effect of vaccination against HPV in the HPV-positive patients not covered by primary prevention on the disappearance of infection.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-17 07:50:15","doi":"10.21203/rs.3.rs-4594994/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-01-21T12:31:22+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-20T17:51:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"135601069351807888641176720837104230583","date":"2025-01-02T11:52:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"205483486667709717903448849151779214036","date":"2024-11-26T02:33:24+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-15T08:51:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"260205551110069757256231761719059129668","date":"2024-10-14T04:51:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"86145885017238407025414915790159773797","date":"2024-09-30T23:00:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"184596809387479415051625079629390639916","date":"2024-09-18T12:43:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"182859092429064499793020812023667322958","date":"2024-07-30T09:20:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"38879535087424603043080802223328352615","date":"2024-07-29T06:43:56+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-20T08:34:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-20T08:17:58+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-06-26T05:19:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-25T08:40:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-06-17T15:06:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"16838c7b-5194-430d-8c6c-b5a3ddf44011","owner":[],"postedDate":"July 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":34552909,"name":"Biological sciences/Immunology/Vaccines"},{"id":34552910,"name":"Health sciences/Oncology"},{"id":34552911,"name":"Health sciences/Health care/Public health/Population screening"}],"tags":[],"updatedAt":"2025-04-14T16:07:01+00:00","versionOfRecord":{"articleIdentity":"rs-4594994","link":"https://doi.org/10.1038/s41598-025-92861-5","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-04-12 16:04:58","publishedOnDateReadable":"April 12th, 2025"},"versionCreatedAt":"2024-07-17 07:50:15","video":"","vorDoi":"10.1038/s41598-025-92861-5","vorDoiUrl":"https://doi.org/10.1038/s41598-025-92861-5","workflowStages":[]},"version":"v1","identity":"rs-4594994","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4594994","identity":"rs-4594994","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}