High-grade cervical intraepithelial neoplasia co-existing with vaginal intraepithelial neoplasia increased the risk of persistent human papillomavirus infection and residual/recurrent disease after LEEP

High-grade cervical intraepithelial neoplasia co-existing with vaginal intraepithelial neoplasia increased the risk of persistent human papillomavirus infection and residual/recurrent disease after LEEP | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article High-grade cervical intraepithelial neoplasia co-existing with vaginal intraepithelial neoplasia increased the risk of persistent human papillomavirus infection and residual/recurrent disease after LEEP Jing Zhang, Yanmei Zhu, Di Yang, Guangcong Liu, Danbo Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4154836/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose Cervical intraepithelial neoplasia (CIN) with co-existent vaginal intraepithelial neoplasia (VaIN) is a challenge in clinical management. This study was aimed to evaluate the association of having co-existent CIN and VaIN with persistent high-risk HPV (HR-HPV) infection and with residual/recurrent disease after treatment. Methods A retrospective study was performed involving women treated for co-existent CIN2/3 and VaIN and those treated for CIN2/3 only between January 2018 and December 2020. CIN2/3 was treated with LEEP, and VaIN was treated with electrocoagulation (fulguration) at the time of CIN treatment. First follow-up was conducted by HPV-based testing at 3–6 months after treatment. Persistent HPV infection and residual/recurrent disease after treatment are the outcomes of the study. Univariate and multivariate analyses were used to assess the risk factors of persistent HR-HPV infection and residual/recurrent disease. Results Among 676 women with CIN 2/3, 83 (12.3%) women had co-existent VaIN. Age ≥ 50 years (odds ratio, OR = 3.105, 95% confidence interval, CI = 1.399–6.889) and multiple HPV infections (OR = 2.692, 95% CI = 1.406–5.155) were associated with an increased risk of co-existent CIN and VaIN. At the 1st follow-up, 195 (28.8%) of 676 women had persistent HR-HPV infection, which was more common in women having co-existent CIN and VaIN compared those with CIN only (49.4% vs. 26.0%, P < 0.001). After adjusting for potential confounding factors, co-existent CIN and VaIN was an independent risk factor for persistent HR-HPV infection (OR = 2.844, 95% CI = 1.446–5.595) and for residual/recurrent disease (OR = 4.876, 95% CI = 1.131–21.028) after treatment. Conclusions Co-existent CIN and VaIN increased the risk of persistent HR-HPV infection and residual/recurrent disease after treatment. Close follow up was proper for women having co-existent CIN and VaIN. high-grade cervical intraepithelial neoplasia vaginal intraepithelial neoplasia persistent high-risk human papillomavirus infection residual/recurrent disease loop electrosurgical excision procedure Figures Figure 1 A take-home message CIN2/3 co-existing with VaIN was associated with increased persistence of HR-HPV and increased rate of residual/recurrent disease after LEEP. CIN2/3 women with co-existing VaIN after LEEP should be closely monitored. Colposcopy should assess the cervix and the entire vagina. 1 Introduction Cervical cancer is the fourth most common female cancer worldwide and a significant health problem for women [ 1 ]. Early identification and treatment of cervical intraepithelial neoplasia (CIN) plays an important role in the prevention of cervical cancer. The recommended treatment for high-grade CIN (CIN2/3) is mainly cervical excision including cold knife conization (CKC) and loop electrosurgical excision procedure (LEEP) [ 2 ]. Even if CKC or LEEP can effectively remove the lesion and eradicate human papillomavirus (HPV) infections mostly, these women have a higher risk of recurrent disease and progression to cervical cancer compared with the general population [ 3 ]. Persistent high-risk HPV (HR-HPV) infection during follow-up was shown a strong and independent predictor of residual/recurrent CIN after conization [ 4 ]. Thus, determining risks of persistent HR-HPV infection after cervical excision is useful. In recent years, the incidence of high-grade CIN co-existing with vaginal intraepithelial neoplasia (VaIN) has increased, which has gradually attracted the attention of clinicians [ 5 ]. The incidence of VaIN progressing to vaginal squamous cell carcinoma ranges between 2% and 7% [ 6 ]. High-grade VaIN (VaIN 2/3) have premalignant potential and should be treated. VaIN1 associated with high-grade CIN or vulva intraepithelial neoplasia (VIN) have lower spontaneous regression (67%) than those not associated with high-grade CIN or VIN (91%) [ 7 ]. So, while treating high-grade CIN, VaIN should also be addressed. Various treatment options have been adopted for management of VaIN, including topical agents, ablation, excision and radiotherapy [ 8 ]. Treatment should be individualized. The ablation therapies include CO2 laser vaporization, photodynamic therapy, electrocoagulation (fulguration) and so on. Electrocoagulation is a good option in therapy of VaIN [ 9 ]. LEEP and electrocoagulation using the same device are suitable for patients with co-existent CIN and VaIN. However, women with VaIN are at high-risk of recurrence [ 10 ]. If high-grade CIN and VaIN exist simultaneously, even if treated simultaneously, the effect of co-existing with VaIN on persistent HPV infection and residual/recurrent disease after high-grade CIN treatment is still unclear, and it is worth further research. Therefore, in the present study, the association of co-existent CIN2/3 and VaIN with persistent HR-HPV infection and with residual/recurrent disease was evaluated in women who received LEEP for CIN2/3 and electrocoagulation for VaIN. In addition, other clinical risk factors were determined. 2 Material and methods 2.1 Study population We conducted a retrospective study of women with histologically‑confirmed high-grade CIN treated by LEEP from January 2018 to December 2020 at Liaoning cancer Hospital and institute, China medical University. If high-grade CIN co-existed with VaIN, electrocoagulation of vaginal lesion was performed at the same time as LEEP. Exclusion criteria were the following: 1) postoperative pathology upgraded to microinvasion or invasive carcinoma; 2) lack of follow‑up data; 3) second conization or total hysterectomy conducted within 3 months after LEEP; 4) conditions assumed to interact with HPV acquisition or CIN progression including autoimmune disorders, genetic disorders, or organ transplantation; 5) pregnant women. 2.2 Clinical data Demographic and clinicopathological data were collected from each patient. Information was obtained regarding age at the time of conization, parity, types of transformation zone, results of liquid-based cytology (LBC), and results of preoperative and postoperative HPV infection, preoperative co-existence with VaIN status, grade of dysplasia in the excised cone, margin status in the excised cone, and biopsy histological result at follow-up. Assessment of the resection margins was further subdivided into ectocervical only, endocervical only, or both margins. The LBC method (ThinPrep®, Hologic, Marlbororgh, MA, USA) was used for cytology. LBC results were evaluated according to the 2014 Bethesda System. HR-HPV DNA was detected using the Digene Hybrid Capture 2 (HC2) test (Digene Co., Gaithersburg, MD, USA). A result was considered positive when the relative light units/positive control (RLU/PC) ratio was > 1. The RLU/PC ratio is considered a semiquantitative measure of the amount of high-risk HPV DNA. HPV DNA was genotyped with the HPV GenoArray test kit (Hybribio Ltd., Kowloon Bay, Hong Kong) using both DNA amplification and a flow-through hybridization technique [ 11 ]. A total of 21 genotypes (HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58, HPV59, and HPV68, HPV53, HPV66, HPV6, HPV11, HPV42, HPV43, HPV44, and CP8304) were screened. Colposcopy was performed in the Cervical Disease Clinic. The cervix, vagina, and vulva were evaluated comprehensively under colposcopy. Colposcopy-guided biopsies were performed if suspicious lesions were found. Biopsy tissue sections were independently assessed by two expert pathologists. All LEEP operations were performed under the guidance of colposcopy, and the whole vagina was evaluated at the same time. 2.3 Follow-up The 1st follow-up visit was between 3–6 months after treatment, and follow-up visits occurred every 6–12 months thereafter. At each follow-up visit, HC2 HPV DNA test and LBC test were performed for each woman, and if these tests indicated any abnormalities, colposcopy-directed biopsy of the cervix or endocervical curettage was performed. Diagnosed residual/recurrent disease was defined as histologically confirmed CIN2/3 and/or VaIN2/3 on biopsy taken at colposcopy during any of the follow‑up examinations. 2.4 Statistical analysis When data were abnormally distributed, quantitative variables were presented as the median and interquartile range (IQR), and the Mann-Whitney U test was used to compare differences. Pearson’s χ2 test was used for univariate statistical analysis (Fisher’s exact test was used for small sample sizes) of the risk factors associated with co-existent CIN2/3 and VaIN status. Multivariate logistic regression analysis was performed to identify independent risk factors. Univariable analyses were performed to quantify the association between independent variables and binary outcomes using logistic regression analyses for categorical variables. Multivariate logistic regression analyses were used to test the role of co-existent CIN2/3 and VaIN on the risk of persistent HR-HPV infection and residual/recurrence during follow-up, adjusting for confounding effects. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CI). All data analyses were performed with the SPSS version 22.0 software (SPSS Inc., Chicago, IL, USA). A p -value < 0.05 was considered to indicate statistical significance. 2.5 Ethics Statement The ethical committee of Liaoning Cancer Hospital and Institute approved this retrospective study (reference number: 20230162). 3 Results 3.1 General characteristics A total of 676 women with CIN2/3 were eligible for this study, including 83 (12.3%) with co-existing VaIN (48 cases of VaIN1, 35 cases of VaIN2/3) and 593 (87.7%) without VaIN (Fig. 1 ). The clinicopathological characteristics are shown in Table 1 including comparison based on co-existent CIN and VaIN status. Among the eligible women in the present study, the age ranged from 20 to 68 years at the time of treatment. The median age of women with co-existent CIN and VaIN (43 years, IQR 35–52) was higher than that of CIN women without VaIN (39 years, IQR 33–46; p < 0.001). Preoperative HPV testing results were available for 638 women and 613 (96.1%) women had HR-HPV infection. Both CIN groups (with and without VaIN) were similar in terms of prevalence of HPV16/18 infection (62.3% vs. 62.6%, p = 0.960). Multiple HR-HPV infections were significantly more common in women with co-existent CIN and VaIN compared with CIN women without VaIN (52.1% vs. 28.2%, χ2 = 11.373, p = 0.001). Most of the women with co-existent CIN and VaIN were cervical type III transformation zone, which was statistically different from CIN women without VaIN (63.3% vs. 44.8%, χ2 = 9.650, p = 0.008). Table 1 Characteristics of enrolled high-grade CIN women co-existed with VaIN and without VaIN. Characteristics Co-existed with VaIN Without VaIN Univariate Multivariate χ2 P OR (95% CI) P Age, N 83 593 <50, n (%) 53 (63.9) 504 (85.0) 22.425 <0.001 ≥ 50, n (%) 30 (36.1) 89 (15.0) 3.053 (1.372–6.795) 0.006 Parity, N 83 593 <2, n (%) 9 (10.8) 72 (12.1) 0.116 0.733 ≥ 2, n (%) 74 (89.2) 521 (87.9) 0.614 (0.197–1.909) 0.399 Cytology pre-operation, N 64 488 Normal, n (%) 18 (28.1) 138 (28.3) 0.001 0.980 Abnormal, n (%) 46 (71.9) 350 (71.7) HPV infection pre-operation, N 80 558 Negative, n (%) 4 (5.0) 21 (3.8) 0.284 0.540 Positive, n (%) 76 (95.0) 537 (96.2) HPV genotype, N 53 436 Non- HPV16/18, n (%) 20 (37.7) 163 (37.4) 0.002 0.960 HPV16/18, n (%) 33 (62.3) 273 (62.6) 1.357 (0.676–2.725) 0.391 Multiple HPV infection, N 48 386 No, n (%) 23 (47.9) 277 (71.8) 11.373 0.001 Yes, n (%) 25 (52.1) 109 (28.2) 2.710 (1.412–5.201) 0.003 Type of transformation zone, N 79 574 Type I, n (%) 8 (10.1) 78 (13.6) 9.650 0.008 Type II, n (%) 21 (26.6) 239 (41.6) 1.272 (0.397–4.072) 0.685 Type III, n (%) 50 (63.3) 257 (44.8) 1.690 (0.519–5.506) 0.384 Cervical histologic result post-operation, N 83 588 Inflammation or CIN1, n (%) 36 (43.4) 245 (41.7) 0.087 0.768 CIN2/3, n (%) 47 (56.6) 343 (58.3) Margin status, N 83 593 Negative 62 (74.7) 502 (84.7) 5.220 0.027 Positive 21 (25.3) 91 (15.3) 1.835 (0.873–3.857) 0.109 CIN, cervical intraepithelial neoplasia; VaIN, vaginal intraepithelial neoplasia; HPV, human papillomavirus; OR, odds ratio; CI, confidence interval After correcting for confounding effects (parity, HPV16/18 infection, margin status), ≥ 50 years of age (OR = 3.053, 95% CI = 1.372–6.795) and multiple HPV infections (OR = 2.710, 95% CI = 1.412–5.201) but not type III transformation zone (OR = 1.690, 95% CI = 0.519–5.506) were independently associated with an increased risk of co-existent CIN and VaIN. 3.2 Persistent HR-HPV infection at 1st follow-up Among the 676 enrolled CIN women, 195 (28.8%) had persistent HR-HPV infection at the 1st follow-up 3–6 months (average 3.80 months) after treatment. Persistent HR-HPV infection at the 1st follow-up was significantly more common in women with co-existent CIN and VaIN compared with CIN women without VaIN (49.4% vs . 26.0%, p < 0.001). In univariate logistic regression analysis, ≥ 50 years of age (OR = 2.673, 95% CI = 1.778–4.019), multiple preoperative HPV infections (OR = 1.937, 95% CI = 1.253–2.994), cervical type III transformation zone (OR = 1.852, 95% CI = 1.046–3.280), both margins positivity (OR = 3.661, 95% CI = 1.445–9.272), and co-existing VaIN (OR = 2.783, 95% CI = 1.743–4.443) were risk factors for persistent HR-HPV infection at the 1st follow-up (Table 2 ). However, the grade of co-existent VaIN (OR = 1.403, 95% CI = 0.585–3.365) was not associated with persistent HR-HPV infection. Table 2 Risk factors associated with HR-HPV persistent infection at first follow-up after treatment. Characteristics Total HPV persistent infection, n (%) Univariate Multivariate OR (95% CI) P OR (95% CI) P Age <50 557 139 (25.0) 1.0 ≥ 50 119 56 (47.1) 2.673 (1.778–4.019) <0.001 2.522 (1.342–4.738) 0.004 Parity <2 595 167 (28.1) 1.0 0.227 ≥ 2 81 28 (34.6) 1.354 (0.828–2.214) Preoperative cytology NILM 156 53 (34.0) 1.0 ASC-US 160 49 (30.6) 0.858 (0.535–1.375) 0.524 ASC-H 59 17 (28.8) 0.787 (0.409–1.512) 0.472 LSIL 101 30 (29.7) 0.821 (0.478–1.410) 0.475 HSIL 68 9 (13.2) 0.296 (0.136–0.644) 0.002 AGC 6 2 (33.3) 0.972 (0.172–5.478) 0.974 Pre-operative HPV genotype Non- HPV16/18 183 59 (32.2) 1.0 HPV16/18 270 72 (26.7) 0.764 (0.507–1.153) 0.200 0.797 (0.497–1.277) 0.345 Pre-operative multiple HPV infection No 300 74 (24.7) 1.0 Yes 134 52 (38.8) 1.937 (1.253–2.994) 0.003 1.791 (1.102–2.911) 0.019 Type of transformation zone Type I 86 18 (20.9) 1.0 Type II 260 67 (25.8) 1.311 (0.728–2.364) 0.367 Type III 307 101 (32.9) 1.852 (1.046–3.280) 0.035 1.398 (0.667–2.929) 0.375 Cervical histologic result post-operation Inflammation or CIN1 281 84 (29.9) 1.0 CIN2/3 390 108 (27.7) 0.898 (0.640–1.260) 0.534 Margin status Negative 564 154 (27.3) 1.0 External margin positivity 66 20 (30.3) 1.158 (0.663–2.020) 0.607 Internal margin positivity 27 10 (37.0) 1.566 (0.702–3.495) 0.273 Both margins positivity 19 11 (57.9) 3.661 (1.445–9.272) 0.006 2.235 (0.681–7.329) 0.185 Co-existed with VaIN No 593 154 (26.0) 1.0 Yes 83 41 (49.4) 2.783 (1.743–4.443) <0.001 2.905 (1.472–5.734) 0.002 Grade of co-existent VaIN VaIN1 48 22 (45.8) 1.0 VaIN2/3 35 19 (54.3) 1.403 (0.585–3.365) 0.447 VaIN, vaginal intraepithelial neoplasia; HPV, human papillomavirus; HR-HPV, high-risk human papillomavirus; OR, odds ratio; CI, confidence interval; NILM, negative for intraepithelial lesion or malignancy; ASC-US, atypical squamous cell of undetermined significance; ASC-H, atypical squamous cells, HSIL cannot be excluded; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; AGC, atypical glandular cells. To evaluate the effect of co-existent CIN and VaIN on persistence of HR-HPV at the 1st follow-up after adjusting for potential confounding effects (age, multiple HPV infection, types of transformation zone, margin status, and preoperative HPV16/18 infection), multivariate logistic regression equation was used. The adjusted OR of persistent HR-HPV remained significantly increased among women with co-existent CIN and VaIN (OR = 2.905, 95% CI = 1.472–5.734) compared with CIN women without VaIN (Table 2 ). 3.3 Residual/recurrent disease during follow-up The enrolled women were followed up for 3–40 months, with a median of 6 months (IQR 3–13). The overall rate of residual/recurrent disease was 7.1% (48/676). None case progressed to invasive cancer. Among 676 women, biopsy-confirmed residual/recurrent disease was diagnosed in 32 (4.7%) women during the 1st follow-up evaluation. In addition, 31 (31/32, 96.9%) women had persistent HR-HPV infection. The rate of residual/recurrent disease was 19.3% (16/83) during the 1st follow-up in women with co-existing VaIN and 2.7% (16/593) in subjects without VaIN ( p = 0.01). In multivariate logistic regression analysis, after adjusting for age, margin status, preoperative multiple HPV infection, postoperative cytology and persistent HR-HPV infection, co-existent CIN and VaIN remained associated with residual/recurrent disease (OR = 4.485, 95% CI = 1.055–19.070; Table 3 ). Table 3 Risk factors associated with residual/recurrent disease at first follow-up after treatment. Characteristics Total Residual/recurrent disease, n (%) Univariate Multivariate OR (95% CI) P OR (95% CI) P Age <50 557 18 (3.2) 1.0 ≥ 50 119 14 (11.8) 3.993 (1.926–8.277) <0.001 2.858 (0.697–11.727) 0.145 Parity <2 595 29 (4.9) 1.0 ≥ 2 81 3 (3.7) 0.751 (0.223–2.522) 0.643 Postoperative cytology NILM 588 6 (1.0) 1.0 ASC-US or worse 81 24 (29.6) 40.842 (16.033-104.038) <0.001 34.314 (7.308-161.111) <0.001 Postoperative HR-HPV persistence No 481 1 (0.2) Yes 195 31 (15.9) 90.732 (12.289-669.886) <0.001 22.707 (2.556-201.694) 0.005 Preoperative multiple HPV infection No 300 6 (2.0) 1.0 Yes 134 16 (11.9) 6.644 (2.538–17.392) <0.001 7.731 (1. 720-34.743) 0.008 Type of transformation zone Type I 86 4 (4.7) 1.0 Type II 260 9 (3.5) 0.735 (0.221–2.450) 0.616 Type III 307 19 (6.2) 1.352 (0.448–4.086) 0.593 Margin status Negative 564 18 (3.2) 1.0 External margin positivity 66 6 (9.1) 3.033 (1.160–7.935) 0.024 1.637 (0.262–10.232) 0.598 Internal margin positivity 27 4 (14.8) 5.275 (1.652–16.44) 0.005 12.705 (1.394-115.827) 0.024 Both margins positivity 19 4 (21.1) 8.089 (2.439–26.822) 0.001 3.325 (0.248–44.604) 0.364 Co-existed with VaIN No 593 16 (2.7) 1.0 Yes 83 16 (19.3) 8.612 (4.118–18.008) <0.001 4.485 (1.055–19.070) 0.042 VaIN, vaginal intraepithelial neoplasia; HPV, human papillomavirus; HR-HPV, high-risk human papillomavirus; OR, odds ratio; CI, confidence interval; NILM, negative for intraepithelial lesion or malignancy; ASC-US, atypical squamous cell of undetermined significance; HSIL, high-grade squamous intraepithelial lesion. 4 Discussion The results of this study indicated the co-existence of VaIN in high-grade CIN women is rather common. Risk factors for co-existent CIN and VaIN in this study were ≥ 50 years of age and multiple HPV infections. During follow-up, CIN co-existing with VaIN was associated with increased persistence of HR-HPV and increased rate of residual/recurrent disease in the cervix and/or vagina even after correction for potential confounders. In the past, clinicians paid attention to VaIN after hysterectomy due to CIN 2/3 and stage I cervical cancer. Currently, VaIN is known to typically co-exist with CIN rather than in isolation. In previous studies, co-existent CIN and VaIN was reported in 2.2–15.7% of cases [ 5 , 12 ]. In the present study, co-existent CIN and VaIN was observed in 12.3% of cases. Therefore, co-existent CIN and VaIN has attracted increased attention. Co-existent CIN and VaIN was shown in literature to be associated with menopause, multiparity, multiple HPV infections, high HPV viral load, HPV16 infection, and immunosuppression [ 12 – 14 ]. Consistent with the literature, ≥ 50 years of age and multiple HPV infections were independent risk factors for co-existent CIN and VaIN in the present study. However, the correlation between high HPV viral load and CIN co-existing with VaIN was not found in the present study. It might be that there were fewer cases with HPV viral load results. Unlike CIN, VaIN can be extremely challenging to manage due to its anatomical proximity to the bladder and bowel and difficulty in accessing fornices [ 8 ]. Ablation or excision showed good efficacy for high-grade VaIN [ 14 ]. CIN 2/3 co-existing with VaIN, as multicentric lesion, should be treated at the same time. LEEP for CIN 2/3 and ablation (electrocoagulation or CO2 laser vaporization) for VaIN are good options. A retrospective study of 184 patients with VaIN whose main treatment was electrocoagulation with focal resection showed a primary remission rate of 87.62% [ 9 ]. Electrocoagulation was also safe, with few complications. HR-HPV testing plays an important role in postoperative follow-up. Most HPV infections are gradually cleared after cervical excision [ 15 ]. In several previous studies regarding persistence of HR-HPV after LEEP for CIN 2/3, rates of persistent HPV at 3 months reportedly ranged from 20.4–45.6% [ 15 – 18 ] and at 6 months from 14.3–33.0% [ 18 , 19 ]. Factors associated with persistent HR-HPV included age, lesion grade, resection margin status, multiple HR-HPV infections, specific HPV genotype (such as HPV16, 52, 53, or 58), preoperative viral load, and cytology results [ 18 , 20 – 23 ]. However, in previous studies, the results sometimes differed for each risk factor. For example, advanced age was a significant risk factor for persistent infection after treatment in most of the literature. Nevertheless, Baser E et al . [ 24 ] reported that young woman age was a significant independent predictor of HPV persistence 1 year after the CKC procedure. These discrepancies may be due to different age proportion of enrolled women, various definitions of HR-HPV persistence, and different follow-up time. In the present study, women ≥ 50 years of age had higher prevalence of persistent HR-HPV infection after treatment, which may occur due to reactivation or impaired clearance following hormonal changes and immunological impairment [ 22 ]. Although clinical and prognostic variables associated with persistent HR-HPV infection after treatment have been repeatedly evaluated in cytologic and histological series, data regarding the relationship between HR-HPV persistence after treatment and co-existent CIN and VaIN remain lacking. In the present study, after adjusting for potential confounding effects, such as age, multiple HPV infections, types of transformation zone, margin status, and preoperative HPV16/18 infection, co-existent CIN2/3 and VaIN had a higher tendency to harbor a persistent HR-HPV infection. This may due to the possible pathogenesis of multicentric lesions in the lower genital tract associated with specific HPV genotypes infection in the cervix and vagina respectively [ 25 ]. Therefore, women suffering from co-existent CIN2/3 and VaIN should be closely followed up in the post-treatment period. The overall rate of CIN 2 + recurrence/persistence after LEEP reported in literature was approximately 5–25% [ 3 , 26 ]. Predicting residual/recurrent disease as soon as possible after surgery is important. Residual/recurrence rate was reportedly influenced by menopause, size of the lesions, presence of CIN lesion on margins, HIV positivity, and persistent HR-HPV infection [ 3 , 27 , 28 ]. Although margin status is a convenient predictor of recurrence and a traditional risk marker, it does not appear to be an independent risk factor [ 29 ]. Persistent HR-HPV infection during follow-up is a good predictor. The 2019 ASCCP guidelines recommended that for the first follow-up, HPV-based testing is preferred at 6 months after treatment regardless of the margin status [ 2 ]. The appropriate time for the first follow-up has been explored in other studies [ 30 – 32 ]. The relationship between residual/recurrent disease and CIN co-existing with VaIN has been investigated in only a few studies. Due to the nature of VaIN, recurrence is common even after treatment [ 33 ]. In the present study, the rate of residual/recurrent disease was 19.3% during the 1st follow-up among women with co-existent CIN and VaIN, which was higher than that in CIN women without VaIN (2.7%, p < 0.001). Furthermore, multivariate analysis confirmed that women with co-existent CIN and VaIN require careful and individualized follow-up to avoid these adverse consequences. For women with co-existent CIN2/3 and VaIN, the first follow-up at 3 months after treatment to determine if any residual/recurrent disease is present as soon as possible might be optional, however, the rationality of this scheme needs to be further confirmed with prospective research. The main strengths of the present manuscript compared with previous literature included the high number of cases enrolled, analyses of the relationship between CIN co-existing with VaIN and persistent HR-HPV infection, residual/recurrent disease during follow-up. The present study had several limitations. First, data on other potential factors (age at first sexual intercourse, number of sexual partners, menopause status and smoking history) were lacking. Second, HC2 testing was often used in postoperative follow-up. HR-HPV positivity in the 1st follow-up was defined as persistent infection, and whether it was persistent infection of the same genotype could not be determined. Moreover, this study could not investigate HPV infection in the cervix and vagina separately to clarify whether the HPV infection status in each site was the same. 5 Conclusion In conclusion, we should pay more attention to co-existent CIN and VaIN, as co-existing with VaIN may affect the clearance rate of HPV after LEEP. Compared with CIN women without VaIN, high-grade CIN co-existing with VaIN increased the rate of persistent HR-HPV infection and residual/recurrent disease during follow-up. Co-existent CIN2/3 and VaIN after LEEP and electrocoagulation should be closely monitored. Colposcopy should assess the cervix and the entire vagina. Further prospective studies with long-term follow-up data are necessary to evaluate the clinical implications for these risk factors and disease recurrence. Declarations Funding This study was supported by National Key Research and Development Project "Research and Development of Digital Diagnostic and Medical Equipment" (grant number 2017YFC0114200), Liaoning Province Key Research and Development Project (grant number 2018225037). Conflicts of interest The authors declare that they have no conflict of interest. Author contribution All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Jing Zhang, Yanmei Zhu, Di Yang and Guangcong Liu. The first draft of the manuscript was written by Jing Zhang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Ethics approval The present study was approved by the ethical committee of Liaoning Cancer Hospital and Institute (reference number: 20230162). Consent to participate Informed consent was not required because of the anonymity of the patient records. Consent for publication Not applicable. Availability of data and material The dataset analyzed in this study is available from the corresponding author upon reasonable request. Code availability Not applicable Acknowledgments The authors would like to thank Miss Yumei Xiu, Miss Dan Sun, and Miss Xiaopan Hu for their excellent assistance in this work. References Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71(3):209–249 Perkins RB, Guido RS, Castle PE et al (2020) 2019 ASCCP Risk-Based Management Consensus Guidelines Committee. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. 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BJOG 120(7):887 – 93 Kesic V, Carcopino X, Preti M et al (2023) The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) consensus statement on the management of vaginal intraepithelial neoplasia. Int J Gynecol Cancer 33(4):446–461 Gurumurthy M, Leeson S, Tidy J et al (2020) UK national survey of the management of vaginal intraepithelial neoplasia. J Obstet Gynaecol 40(5):694–698 Chen L, Hu D, Xu S et al (2016) Clinical features, treatment and outcomes of vaginal intraepithelial neoplasia in a Chinese tertiary centre. Ir J Med Sci 185(1):111–114 Kim MK, Lee IH, Lee KH (2018) Clinical outcomes and risk of recurrence among patients with vaginal intraepithelial neoplasia: a comprehensive analysis of 576 cases. J Gynecol Oncol 29(1):e6 Liu SS, Leung RC, Chan KK et al (2010) Evaluation of a newly developed GenoArray human papillomavirus (HPV) genotyping assay and comparison with the Roche Linear Array HPV genotyping assay. J Clin Microbiol 48(3):758–764 Gonzalez-Bosquet E, Mazarico E, Lorente N et al (2017) Risk factors to develop multicentric lesions of the lower genital tract. Eur J Gynaecol Oncol 38(1):10–13 Zhang YY, Xia R, Chen D et al (2022) Analysis of related factors of cervical intraepithelial neoplasia complicated with vaginal intraepithelial neoplasia. Clin Transl Oncol 24(5):902–908 Cho HW, Hong JH, Lee JK (2021) Detection of high-risk human papillomavirus infection and treatment of high-grade vaginal intraepithelial neoplasia: A single-institution study. Int J Gynaecol Obstet 154(2):227–232 Zhang G, Lang J, Shen K et al (2017) High-risk human papillomavirus infection clearance following conization among patients with cervical intraepithelial neoplasm grade 3 aged at least 45 years. Int J Gynaecol Obstet 136(1):47–52 Gosvig CF, Huusom LD, Deltour I et al (2015) Role of human papillomavirus testing and cytology in follow-up after conization. Acta Obstet Gynecol Scand 94(4):405–411 Du R, Meng W, Chen ZF et al (2013) Post-treatment human papillomavirus status and recurrence rates in patients treated with loop electrosurgical excision procedure conization for cervical intraepithelial neoplasia. Eur J Gynaecol Oncol 34(6):548–551 Kim YT, Lee JM, Hur SY et al (2010) Clearance of human papillomavirus infection after successful conization in patients with cervical intraepithelial neoplasia. Int J Cancer 126(8):1903–1909 Pirtea L, Grigoraş D, Matusz P et al (2016) Human Papilloma Virus Persistence after Cone Excision in Women with Cervical High Grade Squamous Intraepithelial Lesion: A Prospective Study. Can J Infect Dis Med Microbiol 2016: 3076380 Gosvig CF, Huusom LD, Andersen KK et al (2013) Persistence and reappearance of high-risk human papillomavirus after conization. Gynecol Oncol 131(3):661–666 Pirtea L, Grigoraş D, Matusz P et al (2016) Age and HPV type as risk factors for HPV persistence after loop excision in patients with high grade cervical lesions: an observational study. BMC Surg 16(1):70 So KA, Lee IH, Kim TJ et al (2019) Risk factors of persistent HPV infection after treatment for high-grade squamous intraepithelial lesion. Arch Gynecol Obstet 299(1):223–227 Kilic D, Guler T, Atigan A et al (2020) Predictors of Human papillomavirus (HPV) persistence after treatment of high grade cervical lesions; does cervical cytology have any prognostic value in primary HPV screening? Ann Diagn Pathol 49:151626 Baser E, Ozgu E, Erkilinc S et al (2014) Risk factors for human papillomavirus persistence among women undergoing cold-knife conization for treatment of high-grade cervical intraepithelial neoplasia. Int J Gynaecol Obstet 125(3):275–278 Zhang J, Liu G, Cui X et al (2021) Human papillomavirus genotypes and the risk factors associated with multicentric intraepithelial lesions of the lower genital tract: a retrospective study. BMC Infect Dis 21(1):554 Fernández-Montolí ME, Tous S, Medina G et al (2020) Long-term predictors of residual or recurrent cervical intraepithelial neoplasia 2–3 after treatment with a large loop excision of the transformation zone: a retrospective study. BJOG 127(3):377–387 Wu J, Jia Y, Luo M et al (2016) Analysis of Residual/Recurrent Disease and Its Risk Factors after Loop Electrosurgical Excision Procedure for High-Grade Cervical Intraepithelial Neoplasia. Gynecol Obstet Invest 81(4):296–301 Jing L, Dan W, Zhunan L et al (2018) Residual lesions in uterine specimens after loop electrosurgical excision procedure in patients with CIN. Arch Gynecol Obstet 298(4):805–812 Massad LS, Einstein MH, Huh WK et al (2013) 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstet Gynecol 121(4):829–846 Alonso I, Torné A, Puig-Tintoré LM et al (2006) Pre- and post-conization high-risk HPV testing predicts residual/recurrent disease in patients treated for CIN 2–3. Gynecol Oncol 103(2):631–636 Ryu A, Nam K, Kwak J et al (2012) Early human papillomavirus testing predicts residual/recurrent disease after LEEP. J Gynecol Oncol 23(4):217–225 Bruhn LV, Hyldig N, Schledermann D (2022) HPV Test as Test of Cure After Conization for CIN2+: A Nationwide Register-Based Cohort Study. J Low Genit Tract Dis 26(4):287–292 Field A, Bhagat N, Clark S et al (2020) Vaginal Intraepithelial Neoplasia: A Retrospective Study of Treatment and Outcomes Among a Cohort of UK Women. J Low Genit Tract Dis 24(1):43–47 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4154836","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":291795187,"identity":"eceb7d7f-0d81-4e0e-a7d9-d04dcc282574","order_by":0,"name":"Jing Zhang","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Zhang","suffix":""},{"id":291795188,"identity":"9881aa82-e396-43af-b3c8-02609f5da441","order_by":1,"name":"Yanmei Zhu","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yanmei","middleName":"","lastName":"Zhu","suffix":""},{"id":291795189,"identity":"35794f09-91e3-4ab5-8167-0988c4b21408","order_by":2,"name":"Di Yang","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Di","middleName":"","lastName":"Yang","suffix":""},{"id":291795190,"identity":"3aa9dd23-14a1-4857-9055-5776d9857002","order_by":3,"name":"Guangcong Liu","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Guangcong","middleName":"","lastName":"Liu","suffix":""},{"id":291795191,"identity":"e8975f28-179f-4d5a-9013-ab524a70049a","order_by":4,"name":"Danbo Wang","email":"data:image/png;base64,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","orcid":"https://orcid.org/0000-0002-8925-364X","institution":"Cancer Hospital of China Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Danbo","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2024-03-23 14:33:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4154836/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4154836/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55099138,"identity":"c1b75972-386f-46a8-9122-11f023932d03","added_by":"auto","created_at":"2024-04-22 15:10:02","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":164991,"visible":true,"origin":"","legend":"\u003cp\u003eFlow diagram of the study population.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4154836/v1/0165e17d19d6481ef9110caa.jpg"},{"id":56457228,"identity":"d42be9e2-a7f8-451e-94ac-2c545f016ff9","added_by":"auto","created_at":"2024-05-14 12:27:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1113203,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4154836/v1/53263559-94fd-486f-9241-35634f4e4783.pdf"}],"financialInterests":"","formattedTitle":"High-grade cervical intraepithelial neoplasia co-existing with vaginal intraepithelial neoplasia increased the risk of persistent human papillomavirus infection and residual/recurrent disease after LEEP","fulltext":[{"header":"A take-home message","content":"\u003cul\u003e\n \u003cli\u003eCIN2/3 co-existing with VaIN was associated with increased persistence of HR-HPV and increased rate of residual/recurrent disease after LEEP.\u003c/li\u003e\n \u003cli\u003eCIN2/3 women with co-existing VaIN after LEEP should be closely monitored. Colposcopy should assess the cervix and the entire vagina.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"1 Introduction","content":"\u003cp\u003eCervical cancer is the fourth most common female cancer worldwide and a significant health problem for women [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Early identification and treatment of cervical intraepithelial neoplasia (CIN) plays an important role in the prevention of cervical cancer. The recommended treatment for high-grade CIN (CIN2/3) is mainly cervical excision including cold knife conization (CKC) and loop electrosurgical excision procedure (LEEP) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Even if CKC or LEEP can effectively remove the lesion and eradicate human papillomavirus (HPV) infections mostly, these women have a higher risk of recurrent disease and progression to cervical cancer compared with the general population [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Persistent high-risk HPV (HR-HPV) infection during follow-up was shown a strong and independent predictor of residual/recurrent CIN after conization [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Thus, determining risks of persistent HR-HPV infection after cervical excision is useful.\u003c/p\u003e \u003cp\u003eIn recent years, the incidence of high-grade CIN co-existing with vaginal intraepithelial neoplasia (VaIN) has increased, which has gradually attracted the attention of clinicians [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The incidence of VaIN progressing to vaginal squamous cell carcinoma ranges between 2% and 7% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. High-grade VaIN (VaIN 2/3) have premalignant potential and should be treated. VaIN1 associated with high-grade CIN or vulva intraepithelial neoplasia (VIN) have lower spontaneous regression (67%) than those not associated with high-grade CIN or VIN (91%) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. So, while treating high-grade CIN, VaIN should also be addressed. Various treatment options have been adopted for management of VaIN, including topical agents, ablation, excision and radiotherapy [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Treatment should be individualized. The ablation therapies include CO2 laser vaporization, photodynamic therapy, electrocoagulation (fulguration) and so on. Electrocoagulation is a good option in therapy of VaIN [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. LEEP and electrocoagulation using the same device are suitable for patients with co-existent CIN and VaIN. However, women with VaIN are at high-risk of recurrence [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. If high-grade CIN and VaIN exist simultaneously, even if treated simultaneously, the effect of co-existing with VaIN on persistent HPV infection and residual/recurrent disease after high-grade CIN treatment is still unclear, and it is worth further research.\u003c/p\u003e \u003cp\u003eTherefore, in the present study, the association of co-existent CIN2/3 and VaIN with persistent HR-HPV infection and with residual/recurrent disease was evaluated in women who received LEEP for CIN2/3 and electrocoagulation for VaIN. In addition, other clinical risk factors were determined.\u003c/p\u003e"},{"header":"2 Material and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study population\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective study of women with histologically‑confirmed high-grade CIN treated by LEEP from January 2018 to December 2020 at Liaoning cancer Hospital and institute, China medical University. If high-grade CIN co-existed with VaIN, electrocoagulation of vaginal lesion was performed at the same time as LEEP. Exclusion criteria were the following: 1) postoperative pathology upgraded to microinvasion or invasive carcinoma; 2) lack of follow‑up data; 3) second conization or total hysterectomy conducted within 3 months after LEEP; 4) conditions assumed to interact with HPV acquisition or CIN progression including autoimmune disorders, genetic disorders, or organ transplantation; 5) pregnant women.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Clinical data\u003c/h2\u003e \u003cp\u003eDemographic and clinicopathological data were collected from each patient. Information was obtained regarding age at the time of conization, parity, types of transformation zone, results of liquid-based cytology (LBC), and results of preoperative and postoperative HPV infection, preoperative co-existence with VaIN status, grade of dysplasia in the excised cone, margin status in the excised cone, and biopsy histological result at follow-up. Assessment of the resection margins was further subdivided into ectocervical only, endocervical only, or both margins.\u003c/p\u003e \u003cp\u003eThe LBC method (ThinPrep\u0026reg;, Hologic, Marlbororgh, MA, USA) was used for cytology. LBC results were evaluated according to the 2014 Bethesda System.\u003c/p\u003e \u003cp\u003eHR-HPV DNA was detected using the Digene Hybrid Capture 2 (HC2) test (Digene Co., Gaithersburg, MD, USA). A result was considered positive when the relative light units/positive control (RLU/PC) ratio was \u0026gt;\u0026thinsp;1. The RLU/PC ratio is considered a semiquantitative measure of the amount of high-risk HPV DNA. HPV DNA was genotyped with the HPV GenoArray test kit (Hybribio Ltd., Kowloon Bay, Hong Kong) using both DNA amplification and a flow-through hybridization technique [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A total of 21 genotypes (HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58, HPV59, and HPV68, HPV53, HPV66, HPV6, HPV11, HPV42, HPV43, HPV44, and CP8304) were screened.\u003c/p\u003e \u003cp\u003eColposcopy was performed in the Cervical Disease Clinic. The cervix, vagina, and vulva were evaluated comprehensively under colposcopy. Colposcopy-guided biopsies were performed if suspicious lesions were found. Biopsy tissue sections were independently assessed by two expert pathologists. All LEEP operations were performed under the guidance of colposcopy, and the whole vagina was evaluated at the same time.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Follow-up\u003c/h2\u003e \u003cp\u003eThe 1st follow-up visit was between 3\u0026ndash;6 months after treatment, and follow-up visits occurred every 6\u0026ndash;12 months thereafter. At each follow-up visit, HC2 HPV DNA test and LBC test were performed for each woman, and if these tests indicated any abnormalities, colposcopy-directed biopsy of the cervix or endocervical curettage was performed. Diagnosed residual/recurrent disease was defined as histologically confirmed CIN2/3 and/or VaIN2/3 on biopsy taken at colposcopy during any of the follow‑up examinations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical analysis\u003c/h2\u003e \u003cp\u003eWhen data were abnormally distributed, quantitative variables were presented as the median and interquartile range (IQR), and the Mann-Whitney \u003cem\u003eU\u003c/em\u003e test was used to compare differences. Pearson\u0026rsquo;s χ2 test was used for univariate statistical analysis (Fisher\u0026rsquo;s exact test was used for small sample sizes) of the risk factors associated with co-existent CIN2/3 and VaIN status. Multivariate logistic regression analysis was performed to identify independent risk factors. Univariable analyses were performed to quantify the association between independent variables and binary outcomes using logistic regression analyses for categorical variables. Multivariate logistic regression analyses were used to test the role of co-existent CIN2/3 and VaIN on the risk of persistent HR-HPV infection and residual/recurrence during follow-up, adjusting for confounding effects. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CI). All data analyses were performed with the SPSS version 22.0 software (SPSS Inc., Chicago, IL, USA). A \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to indicate statistical significance.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Ethics Statement\u003c/h2\u003e \u003cp\u003e The ethical committee of Liaoning Cancer Hospital and Institute approved this retrospective study (reference number: 20230162).\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.1 General characteristics\u003c/h2\u003e \u003cp\u003eA total of 676 women with CIN2/3 were eligible for this study, including 83 (12.3%) with co-existing VaIN (48 cases of VaIN1, 35 cases of VaIN2/3) and 593 (87.7%) without VaIN (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The clinicopathological characteristics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e including comparison based on co-existent CIN and VaIN status. Among the eligible women in the present study, the age ranged from 20 to 68 years at the time of treatment. The median age of women with co-existent CIN and VaIN (43 years, IQR 35\u0026ndash;52) was higher than that of CIN women without VaIN (39 years, IQR 33\u0026ndash;46; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Preoperative HPV testing results were available for 638 women and 613 (96.1%) women had HR-HPV infection. Both CIN groups (with and without VaIN) were similar in terms of prevalence of HPV16/18 infection (62.3% vs. 62.6%, p\u0026thinsp;=\u0026thinsp;0.960). Multiple HR-HPV infections were significantly more common in women with co-existent CIN and VaIN compared with CIN women without VaIN (52.1% vs. 28.2%, χ2\u0026thinsp;=\u0026thinsp;11.373, p\u0026thinsp;=\u0026thinsp;0.001). Most of the women with co-existent CIN and VaIN were cervical type III transformation zone, which was statistically different from CIN women without VaIN (63.3% vs. 44.8%, χ2\u0026thinsp;=\u0026thinsp;9.650, p\u0026thinsp;=\u0026thinsp;0.008).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of enrolled high-grade CIN women co-existed with VaIN and without VaIN.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\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\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCo-existed with VaIN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eWithout VaIN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c12\" namest=\"c11\"\u003e \u003cp\u003eMultivariate\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eχ2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, \u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e593\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;50, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (63.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e504 (85.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22.425\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;50, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (36.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e89 (15.0)\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3.053 (1.372\u0026ndash;6.795)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity, \u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e593\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;2, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72 (12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0.733\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (89.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e521 (87.9)\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0.614 (0.197\u0026ndash;1.909)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.399\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCytology pre-operation, \u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e488\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (28.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e138 (28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0.980\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormal, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (71.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e350 (71.7)\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHPV infection pre-operation, \u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e558\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.284\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0.540\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 (95.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e537 (96.2)\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHPV genotype, \u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e436\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon- HPV16/18, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (37.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e163 (37.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0.960\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHPV16/18, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (62.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e273 (62.6)\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.357 (0.676\u0026ndash;2.725)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.391\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple HPV infection, \u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e386\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (47.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e277 (71.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.373\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (52.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e109 (28.2)\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2.710 (1.412\u0026ndash;5.201)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of transformation zone, \u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e574\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType I, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (10.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78 (13.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.650\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType II, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (26.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e239 (41.6)\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.272 (0.397\u0026ndash;4.072)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.685\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType III, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (63.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e257 (44.8)\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.690 (0.519\u0026ndash;5.506)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.384\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCervical histologic result post-operation, \u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e588\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInflammation or CIN1, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (43.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e245 (41.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.087\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0.768\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCIN2/3, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47 (56.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e343 (58.3)\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMargin status, \u003cem\u003eN\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e593\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62 (74.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e502 (84.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.220\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (25.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e91 (15.3)\u003c/p\u003e \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\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1.835 (0.873\u0026ndash;3.857)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e0.109\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"12\"\u003eCIN, cervical intraepithelial neoplasia; VaIN, vaginal intraepithelial neoplasia; HPV, human papillomavirus; OR, odds ratio; CI, confidence interval\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAfter correcting for confounding effects (parity, HPV16/18 infection, margin status), \u0026ge; 50 years of age (OR\u0026thinsp;=\u0026thinsp;3.053, 95% CI\u0026thinsp;=\u0026thinsp;1.372\u0026ndash;6.795) and multiple HPV infections (OR\u0026thinsp;=\u0026thinsp;2.710, 95% CI\u0026thinsp;=\u0026thinsp;1.412\u0026ndash;5.201) but not type III transformation zone (OR\u0026thinsp;=\u0026thinsp;1.690, 95% CI\u0026thinsp;=\u0026thinsp;0.519\u0026ndash;5.506) were independently associated with an increased risk of co-existent CIN and VaIN.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Persistent HR-HPV infection at 1st follow-up\u003c/h2\u003e \u003cp\u003eAmong the 676 enrolled CIN women, 195 (28.8%) had persistent HR-HPV infection at the 1st follow-up 3\u0026ndash;6 months (average 3.80 months) after treatment. Persistent HR-HPV infection at the 1st follow-up was significantly more common in women with co-existent CIN and VaIN compared with CIN women without VaIN (49.4% \u003cem\u003evs\u003c/em\u003e. 26.0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eIn univariate logistic regression analysis, \u0026ge; 50 years of age (OR\u0026thinsp;=\u0026thinsp;2.673, 95% CI\u0026thinsp;=\u0026thinsp;1.778\u0026ndash;4.019), multiple preoperative HPV infections (OR\u0026thinsp;=\u0026thinsp;1.937, 95% CI\u0026thinsp;=\u0026thinsp;1.253\u0026ndash;2.994), cervical type III transformation zone (OR\u0026thinsp;=\u0026thinsp;1.852, 95% CI\u0026thinsp;=\u0026thinsp;1.046\u0026ndash;3.280), both margins positivity (OR\u0026thinsp;=\u0026thinsp;3.661, 95% CI\u0026thinsp;=\u0026thinsp;1.445\u0026ndash;9.272), and co-existing VaIN (OR\u0026thinsp;=\u0026thinsp;2.783, 95% CI\u0026thinsp;=\u0026thinsp;1.743\u0026ndash;4.443) were risk factors for persistent HR-HPV infection at the 1st follow-up (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). However, the grade of co-existent VaIN (OR\u0026thinsp;=\u0026thinsp;1.403, 95% CI\u0026thinsp;=\u0026thinsp;0.585\u0026ndash;3.365) was not associated with persistent HR-HPV infection.\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\u003eRisk factors associated with HR-HPV persistent infection at first follow-up after treatment.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\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\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHPV persistent infection, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eMultivariate\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e557\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e139 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e119\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (47.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.673 (1.778\u0026ndash;4.019)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.522 (1.342\u0026ndash;4.738)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e595\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e167 (28.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.227\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (34.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.354 (0.828\u0026ndash;2.214)\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative cytology\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 \u003ctd align=\"left\" colname=\"c8\"\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (34.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASC-US\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (30.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.858 (0.535\u0026ndash;1.375)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.524\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (28.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.787 (0.409\u0026ndash;1.512)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.472\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (29.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.821 (0.478\u0026ndash;1.410)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.475\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (13.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.296 (0.136\u0026ndash;0.644)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAGC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.972 (0.172\u0026ndash;5.478)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.974\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-operative HPV genotype\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon- HPV16/18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (32.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHPV16/18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e270\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.764 (0.507\u0026ndash;1.153)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.797 (0.497\u0026ndash;1.277)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-operative multiple HPV infection\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 (24.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e134\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (38.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.937 (1.253\u0026ndash;2.994)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.791 (1.102\u0026ndash;2.911)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of transformation zone\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (20.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 (25.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.311 (0.728\u0026ndash;2.364)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.367\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e307\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101 (32.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.852 (1.046\u0026ndash;3.280)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.398 (0.667\u0026ndash;2.929)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.375\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCervical histologic result post-operation\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInflammation or CIN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e281\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84 (29.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCIN2/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e390\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108 (27.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.898 (0.640\u0026ndash;1.260)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.534\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMargin status\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e564\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e154 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExternal margin positivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (30.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.158 (0.663\u0026ndash;2.020)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.607\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInternal margin positivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (37.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.566 (0.702\u0026ndash;3.495)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.273\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBoth margins positivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (57.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.661 (1.445\u0026ndash;9.272)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.235 (0.681\u0026ndash;7.329)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.185\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCo-existed with VaIN\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e593\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e154 (26.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (49.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.783 (1.743\u0026ndash;4.443)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.905 (1.472\u0026ndash;5.734)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade of co-existent VaIN\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaIN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (45.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaIN2/3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (54.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.403 (0.585\u0026ndash;3.365)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.447\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eVaIN, vaginal intraepithelial neoplasia; HPV, human papillomavirus; HR-HPV, high-risk human papillomavirus; OR, odds ratio; CI, confidence interval; NILM, negative for intraepithelial lesion or malignancy; ASC-US, atypical\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003esquamous cell of undetermined significance; ASC-H, atypical squamous cells, HSIL cannot be excluded; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; AGC, atypical glandular cells.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTo evaluate the effect of co-existent CIN and VaIN on persistence of HR-HPV at the 1st follow-up after adjusting for potential confounding effects (age, multiple HPV infection, types of transformation zone, margin status, and preoperative HPV16/18 infection), multivariate logistic regression equation was used. The adjusted OR of persistent HR-HPV remained significantly increased among women with co-existent CIN and VaIN (OR\u0026thinsp;=\u0026thinsp;2.905, 95% CI\u0026thinsp;=\u0026thinsp;1.472\u0026ndash;5.734) compared with CIN women without VaIN (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Residual/recurrent disease during follow-up\u003c/h2\u003e \u003cp\u003e The enrolled women were followed up for 3\u0026ndash;40 months, with a median of 6 months (IQR 3\u0026ndash;13). The overall rate of residual/recurrent disease was 7.1% (48/676). None case progressed to invasive cancer. Among 676 women, biopsy-confirmed residual/recurrent disease was diagnosed in 32 (4.7%) women during the 1st follow-up evaluation. In addition, 31 (31/32, 96.9%) women had persistent HR-HPV infection. The rate of residual/recurrent disease was 19.3% (16/83) during the 1st follow-up in women with co-existing VaIN and 2.7% (16/593) in subjects without VaIN (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01). In multivariate logistic regression analysis, after adjusting for age, margin status, preoperative multiple HPV infection, postoperative cytology and persistent HR-HPV infection, co-existent CIN and VaIN remained associated with residual/recurrent disease (OR\u0026thinsp;=\u0026thinsp;4.485, 95% CI\u0026thinsp;=\u0026thinsp;1.055\u0026ndash;19.070; 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\u003eRisk factors associated with residual/recurrent disease at first follow-up after treatment.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\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\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eResidual/recurrent disease, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eUnivariate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eMultivariate\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e557\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e119\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.993 (1.926\u0026ndash;8.277)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.858 (0.697\u0026ndash;11.727)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.145\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e595\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.751 (0.223\u0026ndash;2.522)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.643\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative cytology\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 \u003ctd align=\"left\" colname=\"c8\"\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e588\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASC-US or worse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (29.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40.842 (16.033-104.038)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e34.314 (7.308-161.111)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative HR-HPV persistence\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e481\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.2)\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e195\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (15.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90.732 (12.289-669.886)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e22.707 (2.556-201.694)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative multiple HPV infection\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e134\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (11.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.644 (2.538\u0026ndash;17.392)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.731 (1. 720-34.743)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of transformation zone\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType I\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.735 (0.221\u0026ndash;2.450)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.616\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e307\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.352 (0.448\u0026ndash;4.086)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.593\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMargin status\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e564\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExternal margin positivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.033 (1.160\u0026ndash;7.935)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.637 (0.262\u0026ndash;10.232)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.598\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInternal margin positivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (14.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.275 (1.652\u0026ndash;16.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12.705 (1.394-115.827)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBoth margins positivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.089 (2.439\u0026ndash;26.822)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.325 (0.248\u0026ndash;44.604)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.364\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCo-existed with VaIN\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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e593\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \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 \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (19.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.612 (4.118\u0026ndash;18.008)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.485 (1.055\u0026ndash;19.070)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eVaIN, vaginal intraepithelial neoplasia; HPV, human papillomavirus; HR-HPV, high-risk human papillomavirus; OR, odds ratio; CI, confidence interval; NILM, negative for intraepithelial lesion or malignancy; ASC-US, atypical\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003esquamous cell of undetermined significance; HSIL, high-grade squamous intraepithelial lesion.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eThe results of this study indicated the co-existence of VaIN in high-grade CIN women is rather common. Risk factors for co-existent CIN and VaIN in this study were \u0026ge;\u0026thinsp;50 years of age and multiple HPV infections. During follow-up, CIN co-existing with VaIN was associated with increased persistence of HR-HPV and increased rate of residual/recurrent disease in the cervix and/or vagina even after correction for potential confounders.\u003c/p\u003e \u003cp\u003eIn the past, clinicians paid attention to VaIN after hysterectomy due to CIN 2/3 and stage I cervical cancer. Currently, VaIN is known to typically co-exist with CIN rather than in isolation. In previous studies, co-existent CIN and VaIN was reported in 2.2\u0026ndash;15.7% of cases [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In the present study, co-existent CIN and VaIN was observed in 12.3% of cases. Therefore, co-existent CIN and VaIN has attracted increased attention. Co-existent CIN and VaIN was shown in literature to be associated with menopause, multiparity, multiple HPV infections, high HPV viral load, HPV16 infection, and immunosuppression [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Consistent with the literature, \u0026ge; 50 years of age and multiple HPV infections were independent risk factors for co-existent CIN and VaIN in the present study. However, the correlation between high HPV viral load and CIN co-existing with VaIN was not found in the present study. It might be that there were fewer cases with HPV viral load results. Unlike CIN, VaIN can be extremely challenging to manage due to its anatomical proximity to the bladder and bowel and difficulty in accessing fornices [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Ablation or excision showed good efficacy for high-grade VaIN [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. CIN 2/3 co-existing with VaIN, as multicentric lesion, should be treated at the same time. LEEP for CIN 2/3 and ablation (electrocoagulation or CO2 laser vaporization) for VaIN are good options. A retrospective study of 184 patients with VaIN whose main treatment was electrocoagulation with focal resection showed a primary remission rate of 87.62% [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Electrocoagulation was also safe, with few complications.\u003c/p\u003e \u003cp\u003eHR-HPV testing plays an important role in postoperative follow-up. Most HPV infections are gradually cleared after cervical excision [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In several previous studies regarding persistence of HR-HPV after LEEP for CIN 2/3, rates of persistent HPV at 3 months reportedly ranged from 20.4\u0026ndash;45.6% [\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and at 6 months from 14.3\u0026ndash;33.0% [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Factors associated with persistent HR-HPV included age, lesion grade, resection margin status, multiple HR-HPV infections, specific HPV genotype (such as HPV16, 52, 53, or 58), preoperative viral load, and cytology results [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, in previous studies, the results sometimes differed for each risk factor. For example, advanced age was a significant risk factor for persistent infection after treatment in most of the literature. Nevertheless, Baser E \u003cem\u003eet al\u003c/em\u003e. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] reported that young woman age was a significant independent predictor of HPV persistence 1 year after the CKC procedure. These discrepancies may be due to different age proportion of enrolled women, various definitions of HR-HPV persistence, and different follow-up time. In the present study, women\u0026thinsp;\u0026ge;\u0026thinsp;50 years of age had higher prevalence of persistent HR-HPV infection after treatment, which may occur due to reactivation or impaired clearance following hormonal changes and immunological impairment [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Although clinical and prognostic variables associated with persistent HR-HPV infection after treatment have been repeatedly evaluated in cytologic and histological series, data regarding the relationship between HR-HPV persistence after treatment and co-existent CIN and VaIN remain lacking. In the present study, after adjusting for potential confounding effects, such as age, multiple HPV infections, types of transformation zone, margin status, and preoperative HPV16/18 infection, co-existent CIN2/3 and VaIN had a higher tendency to harbor a persistent HR-HPV infection. This may due to the possible pathogenesis of multicentric lesions in the lower genital tract associated with specific HPV genotypes infection in the cervix and vagina respectively [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Therefore, women suffering from co-existent CIN2/3 and VaIN should be closely followed up in the post-treatment period.\u003c/p\u003e \u003cp\u003eThe overall rate of CIN 2\u0026thinsp;+\u0026thinsp;recurrence/persistence after LEEP reported in literature was approximately 5\u0026ndash;25% [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Predicting residual/recurrent disease as soon as possible after surgery is important. Residual/recurrence rate was reportedly influenced by menopause, size of the lesions, presence of CIN lesion on margins, HIV positivity, and persistent HR-HPV infection [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Although margin status is a convenient predictor of recurrence and a traditional risk marker, it does not appear to be an independent risk factor [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Persistent HR-HPV infection during follow-up is a good predictor. The 2019 ASCCP guidelines recommended that for the first follow-up, HPV-based testing is preferred at 6 months after treatment regardless of the margin status [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The appropriate time for the first follow-up has been explored in other studies [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. The relationship between residual/recurrent disease and CIN co-existing with VaIN has been investigated in only a few studies. Due to the nature of VaIN, recurrence is common even after treatment [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In the present study, the rate of residual/recurrent disease was 19.3% during the 1st follow-up among women with co-existent CIN and VaIN, which was higher than that in CIN women without VaIN (2.7%, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001). Furthermore, multivariate analysis confirmed that women with co-existent CIN and VaIN require careful and individualized follow-up to avoid these adverse consequences. For women with co-existent CIN2/3 and VaIN, the first follow-up at 3 months after treatment to determine if any residual/recurrent disease is present as soon as possible might be optional, however, the rationality of this scheme needs to be further confirmed with prospective research.\u003c/p\u003e \u003cp\u003eThe main strengths of the present manuscript compared with previous literature included the high number of cases enrolled, analyses of the relationship between CIN co-existing with VaIN and persistent HR-HPV infection, residual/recurrent disease during follow-up.\u003c/p\u003e \u003cp\u003eThe present study had several limitations. First, data on other potential factors (age at first sexual intercourse, number of sexual partners, menopause status and smoking history) were lacking. Second, HC2 testing was often used in postoperative follow-up. HR-HPV positivity in the 1st follow-up was defined as persistent infection, and whether it was persistent infection of the same genotype could not be determined. Moreover, this study could not investigate HPV infection in the cervix and vagina separately to clarify whether the HPV infection status in each site was the same.\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eIn conclusion, we should pay more attention to co-existent CIN and VaIN, as co-existing with VaIN may affect the clearance rate of HPV after LEEP. Compared with CIN women without VaIN, high-grade CIN co-existing with VaIN increased the rate of persistent HR-HPV infection and residual/recurrent disease during follow-up. Co-existent CIN2/3 and VaIN after LEEP and electrocoagulation should be closely monitored. Colposcopy should assess the cervix and the entire vagina. Further prospective studies with long-term follow-up data are necessary to evaluate the clinical implications for these risk factors and disease recurrence.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by National Key Research and Development Project \u0026quot;Research and Development of Digital Diagnostic and Medical Equipment\u0026quot; (grant number 2017YFC0114200), Liaoning Province Key Research and Development Project (grant number 2018225037).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Jing Zhang, Yanmei Zhu, Di Yang and Guangcong Liu. The first draft of the manuscript was written by Jing Zhang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe present study was approved by the ethical committee of Liaoning Cancer Hospital and Institute (reference number: 20230162).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was not required because of the anonymity of the patient records.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dataset analyzed in this study is available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Miss Yumei Xiu, Miss Dan Sun, and Miss Xiaopan Hu for their excellent assistance in this work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71(3):209\u0026ndash;249\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePerkins RB, Guido RS, Castle PE et al (2020) 2019 ASCCP Risk-Based Management Consensus Guidelines Committee. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis 24(2):102\u0026ndash;131\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOuh YT, Cho HW, Kim SM et al (2020) Risk factors for type-specific persistence of high-risk human papillomavirus and residual/recurrent cervical intraepithelial neoplasia after surgical treatment. Obstet Gynecol Sci 63(5):631\u0026ndash;642\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKocken M, Helmerhorst TJ, Berkhof J et al (2011) Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: a long-term multi-cohort study. 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Int J Gynecol Cancer 33(4):446\u0026ndash;461\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGurumurthy M, Leeson S, Tidy J et al (2020) UK national survey of the management of vaginal intraepithelial neoplasia. J Obstet Gynaecol 40(5):694\u0026ndash;698\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen L, Hu D, Xu S et al (2016) Clinical features, treatment and outcomes of vaginal intraepithelial neoplasia in a Chinese tertiary centre. Ir J Med Sci 185(1):111\u0026ndash;114\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim MK, Lee IH, Lee KH (2018) Clinical outcomes and risk of recurrence among patients with vaginal intraepithelial neoplasia: a comprehensive analysis of 576 cases. 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Clin Transl Oncol 24(5):902\u0026ndash;908\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCho HW, Hong JH, Lee JK (2021) Detection of high-risk human papillomavirus infection and treatment of high-grade vaginal intraepithelial neoplasia: A single-institution study. Int J Gynaecol Obstet 154(2):227\u0026ndash;232\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang G, Lang J, Shen K et al (2017) High-risk human papillomavirus infection clearance following conization among patients with cervical intraepithelial neoplasm grade 3 aged at least 45 years. Int J Gynaecol Obstet 136(1):47\u0026ndash;52\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGosvig CF, Huusom LD, Deltour I et al (2015) Role of human papillomavirus testing and cytology in follow-up after conization. Acta Obstet Gynecol Scand 94(4):405\u0026ndash;411\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDu R, Meng W, Chen ZF et al (2013) Post-treatment human papillomavirus status and recurrence rates in patients treated with loop electrosurgical excision procedure conization for cervical intraepithelial neoplasia. Eur J Gynaecol Oncol 34(6):548\u0026ndash;551\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim YT, Lee JM, Hur SY et al (2010) Clearance of human papillomavirus infection after successful conization in patients with cervical intraepithelial neoplasia. Int J Cancer 126(8):1903\u0026ndash;1909\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePirtea L, Grigoraş D, Matusz P et al (2016) Human Papilloma Virus Persistence after Cone Excision in Women with Cervical High Grade Squamous Intraepithelial Lesion: A Prospective Study. \u003cem\u003eCan J Infect Dis Med Microbiol\u003c/em\u003e 2016: 3076380\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGosvig CF, Huusom LD, Andersen KK et al (2013) Persistence and reappearance of high-risk human papillomavirus after conization. Gynecol Oncol 131(3):661\u0026ndash;666\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePirtea L, Grigoraş D, Matusz P et al (2016) Age and HPV type as risk factors for HPV persistence after loop excision in patients with high grade cervical lesions: an observational study. BMC Surg 16(1):70\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSo KA, Lee IH, Kim TJ et al (2019) Risk factors of persistent HPV infection after treatment for high-grade squamous intraepithelial lesion. Arch Gynecol Obstet 299(1):223\u0026ndash;227\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKilic D, Guler T, Atigan A et al (2020) Predictors of Human papillomavirus (HPV) persistence after treatment of high grade cervical lesions; does cervical cytology have any prognostic value in primary HPV screening? Ann Diagn Pathol 49:151626\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaser E, Ozgu E, Erkilinc S et al (2014) Risk factors for human papillomavirus persistence among women undergoing cold-knife conization for treatment of high-grade cervical intraepithelial neoplasia. Int J Gynaecol Obstet 125(3):275\u0026ndash;278\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang J, Liu G, Cui X et al (2021) Human papillomavirus genotypes and the risk factors associated with multicentric intraepithelial lesions of the lower genital tract: a retrospective study. BMC Infect Dis 21(1):554\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFern\u0026aacute;ndez-Montol\u0026iacute; ME, Tous S, Medina G et al (2020) Long-term predictors of residual or recurrent cervical intraepithelial neoplasia 2\u0026ndash;3 after treatment with a large loop excision of the transformation zone: a retrospective study. BJOG 127(3):377\u0026ndash;387\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu J, Jia Y, Luo M et al (2016) Analysis of Residual/Recurrent Disease and Its Risk Factors after Loop Electrosurgical Excision Procedure for High-Grade Cervical Intraepithelial Neoplasia. Gynecol Obstet Invest 81(4):296\u0026ndash;301\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJing L, Dan W, Zhunan L et al (2018) Residual lesions in uterine specimens after loop electrosurgical excision procedure in patients with CIN. Arch Gynecol Obstet 298(4):805\u0026ndash;812\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMassad LS, Einstein MH, Huh WK et al (2013) 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. \u003cem\u003eObstet Gynecol\u003c/em\u003e 121(4):829\u0026ndash;846\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlonso I, Torn\u0026eacute; A, Puig-Tintor\u0026eacute; LM et al (2006) Pre- and post-conization high-risk HPV testing predicts residual/recurrent disease in patients treated for CIN 2\u0026ndash;3. Gynecol Oncol 103(2):631\u0026ndash;636\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRyu A, Nam K, Kwak J et al (2012) Early human papillomavirus testing predicts residual/recurrent disease after LEEP. J Gynecol Oncol 23(4):217\u0026ndash;225\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBruhn LV, Hyldig N, Schledermann D (2022) HPV Test as Test of Cure After Conization for CIN2+: A Nationwide Register-Based Cohort Study. J Low Genit Tract Dis 26(4):287\u0026ndash;292\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eField A, Bhagat N, Clark S et al (2020) Vaginal Intraepithelial Neoplasia: A Retrospective Study of Treatment and Outcomes Among a Cohort of UK Women. J Low Genit Tract Dis 24(1):43\u0026ndash;47\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"high-grade cervical intraepithelial neoplasia, vaginal intraepithelial neoplasia, persistent high-risk human papillomavirus infection, residual/recurrent disease, loop electrosurgical excision procedure","lastPublishedDoi":"10.21203/rs.3.rs-4154836/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4154836/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eCervical intraepithelial neoplasia (CIN) with co-existent vaginal intraepithelial neoplasia (VaIN) is a challenge in clinical management. This study was aimed to evaluate the association of having co-existent CIN and VaIN with persistent high-risk HPV (HR-HPV) infection and with residual/recurrent disease after treatment.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective study was performed involving women treated for co-existent CIN2/3 and VaIN and those treated for CIN2/3 only between January 2018 and December 2020. CIN2/3 was treated with LEEP, and VaIN was treated with electrocoagulation (fulguration) at the time of CIN treatment. First follow-up was conducted by HPV-based testing at 3\u0026ndash;6 months after treatment. Persistent HPV infection and residual/recurrent disease after treatment are the outcomes of the study. Univariate and multivariate analyses were used to assess the risk factors of persistent HR-HPV infection and residual/recurrent disease.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 676 women with CIN 2/3, 83 (12.3%) women had co-existent VaIN. Age\u0026thinsp;\u0026ge;\u0026thinsp;50 years (odds ratio, OR\u0026thinsp;=\u0026thinsp;3.105, 95% confidence interval, CI\u0026thinsp;=\u0026thinsp;1.399\u0026ndash;6.889) and multiple HPV infections (OR\u0026thinsp;=\u0026thinsp;2.692, 95% CI\u0026thinsp;=\u0026thinsp;1.406\u0026ndash;5.155) were associated with an increased risk of co-existent CIN and VaIN. At the 1st follow-up, 195 (28.8%) of 676 women had persistent HR-HPV infection, which was more common in women having co-existent CIN and VaIN compared those with CIN only (49.4% vs. 26.0%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). After adjusting for potential confounding factors, co-existent CIN and VaIN was an independent risk factor for persistent HR-HPV infection (OR\u0026thinsp;=\u0026thinsp;2.844, 95% CI\u0026thinsp;=\u0026thinsp;1.446\u0026ndash;5.595) and for residual/recurrent disease (OR\u0026thinsp;=\u0026thinsp;4.876, 95% CI\u0026thinsp;=\u0026thinsp;1.131\u0026ndash;21.028) after treatment.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eCo-existent CIN and VaIN increased the risk of persistent HR-HPV infection and residual/recurrent disease after treatment. Close follow up was proper for women having co-existent CIN and VaIN.\u003c/p\u003e","manuscriptTitle":"High-grade cervical intraepithelial neoplasia co-existing with vaginal intraepithelial neoplasia increased the risk of persistent human papillomavirus infection and residual/recurrent disease after LEEP","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-22 15:09:57","doi":"10.21203/rs.3.rs-4154836/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"96ed5e7f-9601-4ea8-846a-dc224be81d50","owner":[],"postedDate":"April 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-14T12:19:43+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-22 15:09:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4154836","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4154836","identity":"rs-4154836","version":["v1"]},"buildId":"cTy_lsJlmDsVRNrSptgXS","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}