Value of intraoperative post-conisation human papillomavirus testing in predicting residual or recurrence after treatment with a loop electrosurgical excision procedure in women with HR-HPV positive and cervical high-grade squamous intraepithelial lesion

Value of intraoperative post-conisation human papillomavirus testing in predicting residual or recurrence after treatment with a loop electrosurgical excision procedure in women with HR-HPV positive and cervical high-grade squamous intraepithelial lesion | 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 Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Value of intraoperative post-conisation human papillomavirus testing in predicting residual or recurrence after treatment with a loop electrosurgical excision procedure in women with HR-HPV positive and cervical high-grade squamous intraepithelial lesion Weiting Xia, Shenyue Dai, Yan Hu, Simeng Yang, Cheng Chen, Xiaolin Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4528430/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 05 Dec, 2024 Read the published version in BMC Cancer → Version 1 posted 11 You are reading this latest preprint version Abstract Objective To evaluate the feasibility of intraoperative human papillomavirus (IOP-HPV) testing for the prediction of postoperative treatment failure in patients with high-grade squamous intraepithelial lesion (HSIL) undergoing loop electrosurgical excisional procedure (LEEP) Methods A total of 114 women diagnosed with HSIL by biopsy and/or endocervical curettage who underwent LEEP were included in a prospective cohort study. IOP-HPV testing was performed immediately after the procedure. Patients were followed up for 24 months. Logistic regression was used to analyse the factors influencing the residual or recurrent lesions. Further stratified analyses were performed to investigate the differences in prognosis of IOP-HPV positivity in patients of different age and menopausal status. Results 1. Of the 114 patients, 6 (5.26%) were pathologically upgraded to cervical cancer, and 21 (18.42%) were lost to follow-up. Recurrence or residual HSIL lesions occurred in 9.20% (8/87) of cases. Of the 8 women who developed post-treatment HSIL, 7 (26.92%) were positive for IOP-HPV, and only 1 (1.64%) was negative for IOP-HPV (<0.01). 2. Transformation zones of type 2 (P =0.0306) or type 3 (P =0.0446) , diagnosed as LSIL/negative by cervical biopsy (P=0.0396), margin involvement (P=0.0233), positive endocervical curettage after conisation (P=0.0028), intraoperative HPV (P <0.01), cytological abnormalities (P=0.0038), DNA ploidy (P =0.0172), and postoperative HPV (P <0.01) and DNA ploidy (P=0.0078) positivity at 6 months were associated with a higher risk of residual or recurrent lesions. 3. The results of the multivariate regression analysis showed that IOP-HPV positivity was the independent risk factor for residual or recurrent lesions (OR=10.69 , 95% CI:3.41, 33.51, P<0.01). IOP-HPV positivity was strongly associated with the occurrence of residual/recurrent LSIL (OR=6.42 , 95% CI:1.74, 23.70, P=0.0053) and HSIL (OR=32.08 , 95% CI:3.60, 285.64, P=0.0019). 4. Stratified analyses showed that IOP-HPV positive in patients younger than 50 years or premenopausal patients was associated with a significantly higher risk of recurrence or residual lesions (p<0.05). Conclusions IOP-HPV positivity is an independent risk factor for residual or recurrent HSIL lesions. In addition, IOP-HPV positivity was more associated with residual or recurrent lesions in those younger than 50 years or premenopausal. IOP-HPV testing may be of critical clinical value in providing the early and accurate prediction of residual or recurrent lesions. HSIL LEEP IOP-HPV recurrence residual Figures Figure 1 Figure 2 Introduction High-grade squamous intraepithelial lesion (HSIL) of the cervix is caused by persistent high-risk human papillomavirus (HPV) infection[ 1 ], and is a precursor of cervical cancer. Surgical excision by either cold knife conization, laser conization or loop electrosurgical excision procedure (LEEP) is the gold standard treatment[ 2 ]. However, approximately 15% of patients experience varying degrees of residual or recurrence after surgery[ 3 ]. A few studies have evaluated the risk of recurrence after LEEP in women with HSIL, but the results have been inconsistent [ 4 – 8 ]. Age, smoking, lesion size and severity, high-risk human papillomavirus (HR-HPV) type, and persistence of HR-HPV after treatment have each been shown to predict residual or recurrent CIN [ 9 , 10 ]. In addition, margin involvement is a well-established risk factor for treatment failure [ 11 – 15 ]. There is still uncertainty and debate as to which risk factor or combination of factors most accurately predicts recurrence. It is known that most precancerous lesions are located in the transformation zone, and that after excision of the transformation zone, a high percentage of women will have clearance not only of the lesion but also of the HPV infection. Therefore, in women undergoing LEEP where the lesion is completely removed, we would expect the HPV test performed intraoperatively immediately after excision (the IOP HPV test) to be negative, and positive if the excision was incomplete. Therefore, this article attempts to evaluate the feasibility and utility of intraoperative HPV testing (IOP-HPV) performed in the residual cervix immediately after conisation for HSIL, and to determine whether it could be an early marker of disease clearance or persistence. We also analysed the population by age and menopausal status to see if there was a difference in the risk of recurrence. Materials and Methods Data collection This prospective study included 114 patients with HSIL/CIN2-3 who underwent LEEP at the First Affiliated Hospital of Wenzhou Medical University between February 2021 and May 2022. The enrolled patients were all high-risk HPV (HR-HPV) positive and were diagnosed by colposcopically-directed biopsy (CDB) or endocervical curettage (ECC) within 90 days prior to treatment. All women were followed for a minimum of 24 months. Exclusion criteria were the presence of an immunosuppressive disorder and chronic treatment with immunosuppressive drugs, pathology upgraded to cervical cancer after LEEP, or for whom follow-up information was not available. The study was approved by the Institutional Review Board of the First Affiliated Hospital of Wenzhou Medical University (number: KY2020-053). Written informed consent was obtained from all participants. Before LEEP, the abnormal area was delineated with acetic acid and Lugol's solution and removed adjacent to the transformation zone, followed by selective coagulation of the surgical bed with a diathermic coagulation ball. Immediately after LEEP, cervical specimens were collected for IOP-HPV testing, cytology and DNA ploidy analysis of cervical exfoliated cells. ECC was performed at the end of the procedure. HPV genotyping was performed on specimens by PCR and flow fluorescence hybridisation. Cytology samples were interpreted by an experienced pathologist according to the Bethesda system[ 16 ]. For DNA ploidy analysis, after Feulgen staining of cervical cells, the samples were scanned by an automated high-resolution cellular DNA image analysis system. The system analysed multiple parameters of each sample nucleus and automatically performed cell counting and classification according to various characteristic parameters. Follow-up visits were scheduled at 6, 12 and 24 months. At each visit, liquid-based cytology (LBC), HPV testing and DNA ploidy analysis of cervical exfoliated cells were performed. Individuals with any of the three abnormalities underwent colposcopic cervical biopsy, and if the conversion zone was not completely visible or no abnormalities were found on colposcopy, ECC was performed. If all were negative, routine colposcopy and cervical biopsy were performed at 6 and 24 months after surgery. Lesions found within 6 months were considered residual, while those found after 6 months were considered recurrent. If HSIL or more severe lesions were found, a second surgical treatment was performed and follow-up was terminated. Statistical methods In this study, the included participants were categorized as "IOP-HPV positive" and "IOP-HPV negative", continuous variables were described as “mean ± SD (standard deviation)”, categorical variables were described as “N (%)”, and comparisons of differences between the two groups were made using either the Kruskal-Wallis H test or the Chi-square test. We used logistic regression model to assess the association between IOP-HPV and postoperative residual/recurrence. In the analysis we developed three models, model I was unadjusted, model II was adjusted for type of transformation zone, IOP cytology, post-conisation endocervical curettage and model III was adjusted for type of transformation zone, pathology of colposcopy-guided biopsy, IOP cytology, IOP DNA ploidy analysis, cone margin, post-conisation endocervical curettage. Covariates were included as potential confounders in the adjusted models if they changed the estimates of IOP-HPV on postoperative residual/recurrence by more than 10% or were significantly associated with postoperative residual/recurrence. In addition, we performed interaction and stratified analysis by age and menopause in the sensitivity analyses. R language 4.2.1 was used to analyse all data. In all analyses, p < 0.05 was considered statistically significant. Results Patient characteristics During the specified time period, 114 patients met the selection criteria and were included in the study, of whom histological examination of LEEP specimens revealed early cervical cancer (stage IA1/IA2) in 6 (5.26%) cases, of which 21 (18.42%) were lost to follow-up (Fig. 1 ). The median age of all patients was 43 years, ranging from 25 to 62 years, 21.84% (19/87) were menopausal, and the median follow-up was 25 months (range 6–33 months). At baseline, all patients were positive for HR-HPV prior to treatment. Recurrence/residual HSIL lesions occurred in 9.20% (8/87) of cases and all of these patients received follow-up treatment. The median time to diagnosis of HSIL after LEEP was 10 months (range 6–14 months). Of the 8 women who developed HSIL after treatment, seven (26.92%) were positive for IOP-HPV and only one (1.64%) was negative for IOP-HPV (< 0.001). The characteristics of all patients are summarised in Table 1 . Table 1 Patient characteristics Characteristic IOP HPV (-) IOP HPV (+) P-value Age, years Mean ± SD 42.08 ± 9.22 45.50 ± 10.88 0.180 Age, years 0.555 Age<45 Age ≥ 45 37(60.66%) 24(39.34%) 14(53.85%) 12(46.15%) Age, years 0.254 Age<50 Age ≥ 50 45(73.77%) 16(26.23%) 16 (61.54%) 10 (38.46%) Menopause 0.014 Premenopausal Postmenopausal 52(85.25%) 9 (14.75%) 16 (61.54%) 10 (38.46%) Transformation zone (%) 0.010 Type 1 Type 2 Type 3 29(47.54%) 16(26.23%) 16(26.23%) 4 (15.38%) 8 (30.77%) 14 (53.85%) Preoperative HR-HPV test (%) 0.726 Type 16 or 18 positive Other HR-HPV positive 33(54.10%) 28(45.90%) 13 (50.00%) 13 (50.00%) Preoperative cytology (%) 0.751 Negative ASCUS/LSIL/HSIL 19(31.15%) 42(68.85%) 9 (34.62%) 17 (65.38%) Pathology of colposcopy-guided biopsy (%) 0.023 Negative/LSIL HSIL 2(3.28%) 59(96.72%) 5(19.23%) 21 (80.77%) Preoperative ECC 0.019 Negative/LSIL HSIL Not satisfactory 24(39.34%) 18(29.51%) 19(31.15%) 6 (23.08%) 16 (61.54%) 4 (15.38%) IOP/6-months tests IOP cytology 0.001 Negative ≥ASC-US 54(88.52%) 7(11.48%) 15 (57.69%) 11 (42.31%) IOP DNA ploidy analysis 0.008 Negative Positive 44(72.13%) 17 (27.87%) 11(42.31%) 15 (57.69%) Cone margin < 0.001 Negative Positive 58(95.08%) 3 (4.92%) 17(65.38%) 9 (34.62%) Post-conisation ECC 0.003 Negative Positive 60(98.36%) 1 (1.64%) 20(76.92%) 6 (23.08%) Six-month cytology < 0.001 Negative Positive Unavailable 53(86.89%) 0(0.00%) 8 (13.11%) 13(50.00%) 3(11.54%) 10 (38.46%) Six-month DNA ploidy analysis 0.006 Negative Positive Unavailable 47(77.05%) 6(9.84%) 8 (13.11%) 11 (42.31%) 5 (19.23%) 10 (38.46%) Six-month HPV < 0.001 Negative Positive Unavailable 46(75.41%) 7(11.48%) 8 (13.11%) 7 (26.92%) 9 (34.62%) 10 (38.46%) Recurrence < 0.001 No Yes LSIL HSIL 55 (90.16%) 6(9.84%) 5(8.20%) 1 (1.64%) 12(46.15%) 14(53.85%) 7(26.92%) 7 (26.92%) Factors associated with residual/recurrence Univariate regression analysis showed the ORs associated with residual/recurrence (Table 2 ). Patients with cervical transformation zones of type 2 (OR = 5.00; 95% CI = 1.16–21.51; P = 0.0306) and type 3 (OR = 4.29; 95% CI = 1.04–17.74; P = 0.0446) had a higher risk of residual or recurrent lesions than those with transformation zones of type 1. Interestingly, patients whose colposcopy-guided biopsy pathology was LSIL or negative (i.e., tissue from the cervical curettage was diagnosed as HSIL) had a significantly increased risk of postoperative recurrence compared to those whose colposcopy-guided biopsy pathology was HSIL (OR = 0.19; 95% CI = 0.04–0.92; P = 0.0396). Table 2 Factors associated with residual/recurrence. OR (95% CI) P-value Age, years 1.01 (0.96, 1.06) 0.7356 Age, years Age<45 Age ≥ 45 1.0 0.93 (0.34, 2.57) 0.8865 Age, years Age<50 Age ≥ 50 1.0 1.01(0.34, 3.00) 0.9898 Menopause Premenopausal Postmenopausal 1.0 1.78 (0.57, 5.52) 0.3180 Transformation zone Type 1 Type 2 Type 3 1.0 5.00 (1.16, 21.51) 4.29 (1.04, 17.74) 0.0306 0.0446 Preoperative HR-HPV test Type 16 or 18 positive Other HR HPV positive 0.69 (0.25, 1.89) 1.0 0.4681 Preoperative cytology Negative ASCUS/LSIL/HSIL 1.0 0.85 (0.30, 2.43) 0.7588 Pathology of colposcopy-guided biopsy Negative/LSIL HSIL 1.0 0.19 (0.04, 0.92) 0.0396 Preoperative ECC Negative/LSIL HSIL Not satisfactory 1.0 1.57 (0.52, 4.77) 0.31 (0.06, 1.68) 0.4248 0.1751 IOP/6-months tests IOP-HPV Negative Positive 1.0 10.69 (3.41, 33.51) < 0.0001 IOP cytology Negative ≥ASCUS 1.0 5.27 (1.71, 16.27) 0.0038 IOP DNA ploidy analysis Negative Positive 1.0 3.52 (1.25, 9.94) 0.0172 Cone margin Negative Positive 1.0 4.36 (1.22, 15.55) 0.0233 Post-conisation ECC Negative Positive 1.0 28.29 (3.15, 253.80) 0.0028 Six-month cytology Negative Positive Unavailable 1.0 8.15 (0.69, 96.97) 1.57 (0.47, 5.19) 0.0967 0.4612 Six-month DNA ploidy analysis Negative Positive Unavailable 1.0 6.53 (1.64, 26.06) 2.09 (0.60, 7.33) 0.0078 0.2475 Six-month HPV Negative Positive Unavailable 1.0 50.00 (9.85, 253.70) 6.41 (1.35, 30.38) < 0.0001 0.0193 For pathological findings in LEEP specimens, margin involvement was significantly associated with residual/recurrence (P = 0.0233), with ORs of 4.36 (95% CI = 1.22, 15.55). Similarly, a positive result suggested by endocervical curettage after conisation significantly increased the risk of postoperative recurrence (OR = 28.29; 95% CI = 3.15–253.80; P = 0.0028). Patients with intraoperative HPV positivity (OR = 10.69; 95% CI = 3.41–33.51; P < 0.01), cytological abnormalities (OR = 5.27; 95% CI = 1.71–16.27; P = 0.0038) and DNA ploidy positivity (OR = 3.52; 95% CI = 1.25–9.94; P = 0.0172) all had a significantly increased risk of postoperative residual/recurrence. Meanwhile, patients with HPV positivity (OR = 50; 95% CI = 9.85–253.70; P < 0.01) or DNA ploidy positivity (OR = 6.53; 95% CI = 1.64–26.06; P = 0.0078) at 6 months post-operatively also had a significantly increased risk of recurrence, but unexpectedly, the increased risk in patients with abnormal cytology at 6 months post-operatively was not statistically significant. Multifactorial regression analysis of the association between intraoperative HPV positivity and postoperative residual/recurrence Table 3 shows the ORs and 95% CIs of the association between intraoperative HPV infection and postoperative residual or recurrent disease in the three regression models. In model I, we found that IOP-HPV positivity was a risk factor for residual or recurrent disease within 2 years of LEEP in women with HSIL (OR = 10.69, 95% CI:3.41, 33.51, P < 0.01). Based on these results, further analyses showed that IOP-HPV positive was strongly associated with the occurrence of residual/recurrent LSIL (OR = 6.42, 95% CI:1.74, 23.70, P = 0.0053) and HSIL (OR = 32.08, 95% CI:3.60, 285.64, P = 0.0019). More interestingly, the OR was significantly higher in the HSIL group than in the LSIL group (32.08 vs 6.42). In models II and III, the above conclusions remained after adjustment for multiple confounders. IOP-HPV positive showed a robust positive correlation with residual/recurrent cervical lesions. Table 3 Multifactorial analysis of the association between intraoperative HPV positivity and postoperative residual/recurrence Outcome Model I OR(95%CI) P-value Model II OR(95%CI) P-value Model III OR(95%CI) P-value Non- recurrence 1.0 1.0 1.0 recurrence 10.69 (3.41, 33.51) < 0.0001 6.75 (1.85, 24.59) 0.0038 7.47 (1.94, 28.72) 0.0034 LSIL 6.42(1.74, 23.70) 0.0053 4.83 (1.17, 19.95) 0.0295 5.22 (1.20, 22.73) 0.0275 HSIL 32.08 (3.60, 285.64) 0.0019 16.83 (1.20, 236.37) 0.0362 37.52 (1.35, 1045.14) 0.0327 Model I adjust for: None Model II adjust for: Type of transformation zone, IOP cytology, Post-conisation endocervical curettage Model III adjust for: Type of transformation zone, Pathology of colposcopy-guided biopsy, IOP cytology, IOP DNA ploidy analysis, Cone margin, Post-conisation endocervical curettage Stratified associations between IOP-HPV and postoperative residual/recurrent lesion by age and menopause We performed further stratified analyses according to the age of the patients and whether they were menopausal or not (Fig. 2 ). The results showed that there was no significant difference in the risk of postoperative lesion residue/recurrence in patients with IOP HPV positivity, whether they were over or under 45 years of age. In contrast, the risk of postoperative residual/recurrence was significantly higher in patients younger than 50 years than in those older than 50 years. According to models II and III, for patients with IOP-HPV positivity, the risk of postoperative recurrence was 29 times (Interaction-P = 0.0096) and 55.9 times (Interaction-P = 0.0120) higher for patients younger than 50 years, respectively. In addition, premenopausal patients who were HPV-positive intraoperatively had a significantly higher risk of recurrence or residual lesions found postoperatively than postmenopausal patients. According to model II, in non-menopausal women, IOP-HPV positivity is associated with a risk of postoperative lesion recurrence or residual disease that is approximately 59 times higher than in postmenopausal women (Interaction-P = 0.0023). Furthermore, after adjusting for all confounders in model III, the ratio is 130 times higher Interaction-P = 0.0027), which is still statistically significant. Discussion This is one of the few studies to evaluate IOP-HPV testing as an early marker for residual/recurrent cervical high-grade squamous intraepithelial lesion. The present study highlights positive IOP-HPV testing as an important risk factor for recurrence. More interestingly, for these HSIL patients with preoperative HR-HPV positivity, we found that if IOP-HPV testing was positive, being younger than 50 years or non-menopausal was associated with a greater risk of residual or recurrent lesions after LEEP (P<0.05). It has been reported that approximately 15% of women treated for high-grade cervical intraepithelial neoplasia (CIN grade 2 or 3) develop residual or recurrent CIN grade 2 or 3 or cervical cancer [ 3 , 17 – 20 ], with the majority of these diagnosed within 2 years of treatment [ 3 , 18 , 21 , 22 ]. In our study, all patients included were HR-HPV positive preoperatively and we found that 9.2% of them developed recalcitrant/recurrent disease during the two-year postoperative follow-up period, which is consistent with the findings in previous literature. Because of this significant risk, close follow-up of these patients is standard practice. Several risk factors for recurrence of cervical lesions have been suggested in the literature [ 20 , 23 ]. Bogani et al investigated the effect of persistent HPV infection on the risk of CIN2 + recurrence in 545 patients undergoing primary conisation [ 24 ]. The results showed that the risk of recurrence in patients with persistent HPV infection 6 months after cervical conization was 7.46%, whereas the risk of recurrence of cervical lesions in patients with persistent HPV infection 12 months after cervical conization was 13.1%. In addition, the results of a multicentre, 5-year follow-up study of recurrence rates after loop electrosurgery and laser conisation showed that HPV persistence was the only factor associated with 5-year recurrence [ 19 ]. Furthermore, in postmenopausal women, persistent infection with the same HR-HPV genotypes, particularly HPV-18, has been shown to be a risk factor for the development of recurrent CIN2-3 [ 25 ]. Therefore, postoperative HPV infection is considered an important risk factor for HSIL recurrence and is now an important test recommended for postoperative follow-up in clinical practice. However, early identification of patients at higher risk of treatment failure may help to avoid delays in retreatment of these patients and reduce unnecessary visits by women at very low risk of developing the disease. A pilot study by Torne et al was the first to demonstrate that IOP-HPV testing is feasible and accurately predicts treatment failure in patients with CIN2-3. Specifically, treatment failure was found in 12/132 women (9.1%) in the study. The sensitivity, specificity, positive predictive value, and negative predictive value of IOP-HPV testing for treatment failure were superior to other conventional predictors (cone margins, endocervical smears, and 6-month intraoperative cytology), and on multivariate analysis, IOP-HPV was highly associated with treatment failure (OR15.40, 95% CI 1.58-150.42)[ 26 ]. J Rabasa etal performed a similar study to evaluate whether the IOP-HPV test has the same prognostic value as the HPV test performed 6 months after treatment for HSIL to predict treatment failure. They found that the recurrence rate of HSIL was 6%. There was a strong association between a positive IOP-HPV test, a positive 6-month HPV test, a positive HPV 16 genotype, positive surgical margins and HSIL recurrence. The sensitivity, specificity, and positive and negative predictive values of the IOP-HPV test were better than those of the HPV test at 6 months[ 27 ]. Therefore, they believe that this new approach may allow early identification of patients with recurrent disease, which will not delay treatment. Genotyping could be useful in identifying high-risk patients. However, the study was only followed up to 12 months post-surgery and to remedy this, the team subsequently published the results of a 24-month follow-up study showing that the recurrence rate of HSIL was 6.2% (19/304). HPV testing after loop electrosurgical resection predicted HSIL recurrence at 24 months with similar diagnostic accuracy to HPV testing at 6 months. The direct economic savings after the provisional suppression of procedures included in the 6-month control assessment per patient with high-grade intraepithelial lesion was estimated to be 172.8 €[ 28 ]. These studies aroused our intense interest and our results showed similar rates of postoperative recurrence and validated IOP-HPV as an important risk factor for postoperative recurrence. However, among patients with IOP-HPV positivity, is there a difference in the risk of postoperative recurrence according to age or menopausal status? To my knowledge, no relevant study has investigated this question. Menopause has been suggested to be associated with persistent HPV infection. Results from a retrospective cohort study by So KA etal showed that older age (> 50 years) and menopause were associated with persistent HR-HPV infection after cervical conization, and multifactorial analyses showed that menopausal status was the only significant independent predictor of HR-HPV persistence after treatment[ 29 ]. However, a study aimed at analysing the characteristics of HPV distribution, prevalence of infection and age risk in premenopausal and postmenopausal women showed that menopause was not associated with HPV infection[ 30 ]. In addition, a previous study of HPV infection in 20,000 women from nine provinces in China showed that the prevalence of HR-HPV infection in more than 2,000 postmenopausal women (17.2%) was not significantly different from that in non-menopausal women (16.4%) [ 31 ]. It is controversial whether menopause increases a patient's risk of HPV infection. It is also inconclusive whether menopause is associated with recurrence after HSIL treatment. The results of a Korean study showed that menopause (P < 0.001; OR, 3.969), pre- and post-operative HR-HPV load (P < 0.05; OR, 2.430; P < 0.05; OR, 5.351), and infection with multiple HR-HPV types (P < 0.05; OR (2.345) were significantly associated with residual/recurrent CIN after surgery [ 32 ]. However, Gosvig CF et al. found that persistent HR-HPV infection after cervical conization was not associated with age[ 33 ], and the findings of Amal M.A et al. also demonstrated that age and menopause were not associated with postoperative recurrence of HSIL[ 34 ]. This is similar to previously reported studies[ 35 – 37 ]. In our study, the population was all preoperatively HR-HPV positive and pathologically diagnosed with HSIL. We were surprised to find that among them, IOP-HPV positivity at age less than 50 years or premenopausal was more significantly associated with residual/recurrent lesions (including HSIL and LSIL). This observation may be related to more frequent sexual intercourse before age 50 or before menopause. What's more, postmenopausal women were more likely to have cervical adhesions and strictures after LEEP, making it difficult to diagnose recurrent lesions. This needs to be confirmed and investigated in studies with large samples. By identifying the risk factors for HSIL recurrence and residual disease, the best and most precise way to treat HSIL and IOP-HPV positive patients will be explored. This study is one of the few to use intraoperative HPV testing as an early predictor of residual or recurrent cervical HSIL. Our study was performed by the same surgeon to ensure consistency of surgery. There are still some shortcomings of this study. The sample size is small, which may cause some variability in the research results. The follow-up study is expected to address these shortcomings and provide a more in-depth discussion. Conclusion The rate of residual or recurrent lesions after LEEP treatment for HSIL was approximately 9.2%. IOP-HPV positivity was an independent risk factor for residual or recurrent HSIL. In addition, IOP-HPV positivity, age less than 50 years, or premenopausal status were more significantly associated with residual or recurrent lesions. Therefore, IOP-HPV testing for LEEP may have significant clinical value in the early prediction of residual or recurrent high-grade squamous intraepithelial lesions of the cervix, allowing for personalised management and timely follow-up. Larger studies are needed to confirm whether IOP-HPV testing can replace or complement traditional follow-up strategies. Abbreviations ASCUS Atypical squamous cells of undetermined signifcance CDB Colposcopically directed biopsy CIN Cervical intraepithelialneoplasia ECC Endocervical curettage HR-HPV High-risk human papillomavirus HSIL High-grade squamous intraepithelial lesion IOP-HPV Intraoperative post-conisation human papillomavirus LBC Liquid-based cytology TCT ThinPrep cytologic test LEEP Loop electrosurgical excisional procedure LSIL Low-grade squamous intraepithelial lesion Declarations Acknowledgements Not applicable Authors ’ contributions WX and XL had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of data analysis. Conception and design: WX, XL and SD.Acquisition, analysis, or interpretation of data: WX, SY, CC, and XL. Drafting of the manuscript: WX, YH, and XL. Critical revision of the manuscript for important intellectual content: WX, SD and XL. Statistical analysis: WX, XL,CC. Data Collection: SD, SY, and XL.Supervision: YH. All authors read and approved the fnal manuscript. Funding Scientific and Technology Project of Wenzhou (grant number Y20210369) Availability of data and materials The datasets generated and analysed during the current study are not publicly available due avoid unreasonable use by third parties or organizations, but are available from the corresponding author on reasonable request. Ethics approval and consent to participate This study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University. Informed consent was obtained for all patients or family members. In addition, all methods were performed in accordance with the relevant guidelines and regulations. Consent for publication Not applicable. Competing interests The authors declare no competing interests. References Walboomers JMM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. 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Correlation of recurrence rates and times with posttreatment human papillomavirus status in patients treated with loop electrosurgical excision procedure conization for cervical squamous intraepithelial lesions. Int J Gynecol Cancer. 2008;18(1):90–4. SarianLOZ, Derchain SFM, Pitta Dda, Morais R, Rabelo-Santos SS. Factors associated with HPV persistence after treatment for high-grade cervical intra-epithelial neoplasia with large loop excision of the transformation zone (LLETZ). J Clin Virol. 2004;31(4):270–4. Flannelly G, Bolger B, Fawzi H, De A, Monaghan JM. Follow up after LLETZ: could schedules be modified according to risk of recurrence? BJOG. 2001;108(10):1025–30. Serati M, Siesto G, Carollo S, Formenti G, Riva C, Cromi A, et al. Risk factors for cervical intraepithelial neoplasia recurrence after conization: a 10-year study. Eur J Obstet Gynecol Reproductive Biology. 2012;165(1):86–90. Arbyn M, Evangelos Paraskevaidis, Martin-Hirsch P, Prendiville W, Dillner J. Clinical utility of HPV–DNA detection: Triage of minor cervical lesions, follow-up of women treated for high-grade CIN: An update of pooled evidence. Gynecol Oncol. 2005;99(3):S7–11. Arbyn M, Redman CWE, Verdoodt F, Kyrgiou M, Tzafetas M, Ghaem-Maghami S, et al. Incomplete excision of cervical precancer as a predictor of treatment failure: a systematic review and meta-analysis. Lancet Oncol. 2017;18(12):1665–79. Zhang H, Zhang T, You Z, Zhang Y, Positive Surgical Margin HPV, Persistence. Expression of Both TPX2 and PD-L1 Are Associated with Persistence/Recurrence of Cervical Intraepithelial Neoplasia after Cervical Conization. PLoS ONE. 2015;10(12):e0142868. Solomon D, Davey D, Kurman R, Moriarty A, O’Connor D, Prey M, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002;287(16):2114–9. Zielinski GD, Bais AF, Helmerhorst TJM, René HM, Verheijen, Frits, Peter JF, Snijders, et al. HPV Testing and Monitoring of Women After Treatment of CIN 3: Review of the Literature and Meta-analysis. Obstet Gynecol Surv. 2004;59(7):543–53. Melnikow J, McGahan C, Sawaya GF, Ehlen T, Coldman A. Cervical Intraepithelial Neoplasia Outcomes After Treatment: Long-term Follow-up From the British Columbia Cohort Study. JNCI J Natl Cancer Inst. 2009;101(10):721–8. Bogani G, DI Donato V, Sopracordevole F, Ciavattini A, Ghelardi A, Lopez S, et al. Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser Conization: A 5-year follow-up study. Gynecol Oncol. 2020;159(3):636–41. Bogani G, Sopracordevole F, Ciavattini A, Vizza E, Paolo Vercellini, Ghezzi F et al. HPV persistence after cervical surgical excision of high-grade cervical lesions. Cancer Cytopathol. 2023. Feng C, Gu L, Wei Y, Niu J, Yang H, Hong Z et al. Analysis of outcomes following loop electrosurgical excision and clinical features of patients with cervical high-grade squamous intraepithelial lesions with abnormal preoperative endocervical curettage. World J Surg Oncol. 2023;21(1). Bilibio JP, Monego HI, Binda MLA, dos Reis R. Menopausal status is associated with a high risk for residual disease after cervical conization with positive margins. PLoS ONE. 2019;14(6):e0217562. Ruthy Shaco-Levy, Eger G, Dreiher J, Benharroch D, Mihai Meirovitz. Positive Margin Status in Uterine Cervix Cone Specimens is Associated With Persistent/Recurrent High-grade Dysplasia. Int J Gynecol Pathol. 2014;33(1):83–8. Bogani G, Sopracordevole F, Ciavattini A, Vizza E, Paolo Vercellini, Giannini A, et al. Duration of human papillomavirus persistence and its relationship with recurrent cervical dysplasia. Eur J Cancer Prev. 2023;32(6):525–32. Kang WD, Kim SM. Human papillomavirus genotyping as a reliable prognostic marker of recurrence after loop electrosurgical excision procedure for high-grade cervical intraepithelial neoplasia (CIN2-3) especially in postmenopausal women. Menopause. 2016;23(1):81–6. Torné A, Fusté P, Rodríguez-Carunchio L, Alonso I, del Pino M, Nonell R, et al. Intraoperative post-conisation human papillomavirus testing for early detection of treatment failure in patients with cervical intraepithelial neoplasia: a pilot study. BJOG: Int J Obstet Gynecol. 2012;120(4):392–9. Rabasa J, Bradbury M, Sanchez-Iglesias JL, Guerrero D, Forcada C, Alcalde A, et al. Evaluation of the intraoperative human papillomavirus test as a marker of early cure at 12 months after electrosurgical excision procedure in women with cervical high‐grade squamous intraepithelial lesion: a prospective cohort study. BJOG. 2019;127(1):99–105. Jordi Rabasa, Alcalde A, Bradbury M, José Luis Sánchez-Iglesias, Guerrero D, Forcada C et al. Intraoperative Human Papillomavirus Test Predicts 24-Month High-Grade Squamous Intraepithelial Lesion Recurrence Saving Costs: A Prospective Cohort Study. Journal of lower genital tract disease. 2020;24(4):367–71. So KA, Lee IH, Kim TJ, Lee KH. Risk factors of persistent HPV infection after treatment for high-grade squamous intraepithelial lesion. Arch Gynecol Obstet. 2018;299(1):223–7. Shen Y, Xia J, Li H, Xu Y, Xu S. Human papillomavirus infection rate, distribution characteristics, and risk of age in pre- and postmenopausal women. BMC Women’s Health. 2021;21(1). Holt HK, Zhang L, Zhao FH, Hu SY, Zhao XL, Zhang X, et al. Evaluation of multiple primary and combination screening strategies in postmenopausal women for detection of cervical cancer in China. Int J Cancer. 2016;140(3):544–54. Ouh YT, Cho HW, Kim SM, Min KJ, Lee SH, Song JY, et al. Risk factors for type-specific persistence of high-risk human papillomavirus and residual/recurrent cervical intraepithelial neoplasia after surgical treatment. Obstet Gynecol Sci. 2020;63(5):631–42. Gosvig CF, Huusom LD, Andersen KK, Iftner A, Cederkvist L, Svare E, et al. Persistence and reappearance of high-risk human papillomavirus after conization. Gynecol Oncol. 2013;131(3):661–6. Abdulaziz AMA, You X, Liu L, Sun Y, Zhang J, Sun S, et al. Management of high-grade squamous intraepithelial lesion patients with positive margin after LEEP conization. Medicine. 2021;100(20):e26030. Chen J, Wang Z, Wang Z, Yang X. The risk factors of residual lesions and recurrence of the high-grade cervical intraepithelial lesions (HSIL) patients with positive-margin after conization. Medicine. 2018;97(41):e12792. Leguevaque P, Motton S, Decharme A, Soulé-Tholy M, Escourrou G, Hoff J. Predictors of recurrence in high-grade cervical lesions and a plan of management. Eur J Surg Oncol. 2010;36(11):1073–9. Park JY, Lee KH, Dong SM, Kang S, Park SY, Seo SS. The association of pre-conization high-risk HPV load and the persistence of HPV infection and persistence/recurrence of cervical intraepithelial neoplasia after conization. Gynecol Oncol. 2008;108(3):549–54. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 05 Dec, 2024 Read the published version in BMC Cancer → Version 1 posted Editorial decision: Revision requested 30 Oct, 2024 Reviews received at journal 30 Oct, 2024 Reviewers agreed at journal 20 Oct, 2024 Reviewers agreed at journal 27 Jun, 2024 Reviews received at journal 21 Jun, 2024 Reviewers agreed at journal 16 Jun, 2024 Reviewers invited by journal 12 Jun, 2024 Editor invited by journal 06 Jun, 2024 Editor assigned by journal 05 Jun, 2024 Submission checks completed at journal 05 Jun, 2024 First submitted to journal 04 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board 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-4528430","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":315977774,"identity":"81a62e92-2d24-40e8-844f-66015b7c89d6","order_by":0,"name":"Weiting Xia","email":"","orcid":"","institution":"the First Affiliated Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Weiting","middleName":"","lastName":"Xia","suffix":""},{"id":315977775,"identity":"3c0903af-848a-4c8e-a250-c251600e1b9b","order_by":1,"name":"Shenyue Dai","email":"","orcid":"","institution":"the First Affiliated Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shenyue","middleName":"","lastName":"Dai","suffix":""},{"id":315977777,"identity":"6ad64da3-8b73-43db-a753-a9c9bcc4f375","order_by":2,"name":"Yan Hu","email":"","orcid":"","institution":"the First Affiliated Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Hu","suffix":""},{"id":315977778,"identity":"32bd4e5b-bb19-41c4-b339-a6a5ac664651","order_by":3,"name":"Simeng Yang","email":"","orcid":"","institution":"the First Affiliated Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Simeng","middleName":"","lastName":"Yang","suffix":""},{"id":315977780,"identity":"2ea97af4-8047-4553-b1af-d8f6fed6045c","order_by":4,"name":"Cheng Chen","email":"","orcid":"","institution":"the First Affiliated Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Cheng","middleName":"","lastName":"Chen","suffix":""},{"id":315977782,"identity":"6bc14165-71b3-4c51-a93e-9d5c483a49f1","order_by":5,"name":"Xiaolin Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYBACfvbmA8Y//9gws7E3EKlFsudYQjFjQxo7H88BIrUY3MhR+MzYcJhfTiKBWFsachg3F+44LM0m+XjjDYYam2iCWvgZzh42nnkm3ZhNOq3YguFYWm4DQVsa+9IMeNisk9mkc8wkgC4krMXgMI/5Dx425vo2yTPEajnGY2DM2+bMzCbBQ6QWyR62BMMZZ9KY2XiAfkkgxi/88o8PGHyosGGWbz+88caHGhvCWlAcSXTUIGkhVccoGAWjYBSMDAAAv9Y9D5KpyWAAAAAASUVORK5CYII=","orcid":"","institution":"the First Affiliated Hospital of Wenzhou Medical University","correspondingAuthor":true,"prefix":"","firstName":"Xiaolin","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2024-06-04 13:33:55","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4528430/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4528430/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12885-024-13272-9","type":"published","date":"2024-12-05T15:58:08+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":59052415,"identity":"24060137-cfe2-408e-949b-8102f66b35f8","added_by":"auto","created_at":"2024-06-25 20:15:48","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":896651,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the study.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4528430/v1/fdf66d3ec90b722c86c7ba14.jpg"},{"id":59052414,"identity":"b50571cd-5421-4ffb-9bdb-388e05352edd","added_by":"auto","created_at":"2024-06-25 20:15:48","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":712735,"visible":true,"origin":"","legend":"\u003cp\u003eStratified associations between IOP-HPV positivity and postoperative residual/recurrence according to baseline characteristics. \u003csup\u003ea \u003c/sup\u003ewas adjusted for type of transformation zone, IOP cytology, post-conisation endocervical curettage. \u003csup\u003eb \u003c/sup\u003ewas adjusted for type of transformation zone, pathology of colposcopy-guided biopsy, IOP cytology, IOP DNA ploidy analysis, cone margin, post-conisation endocervical curettage.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4528430/v1/498cc99c1dff4ae7bc6d740b.jpg"},{"id":70965305,"identity":"06668d58-9d8b-47d1-9af6-be415d33eec3","added_by":"auto","created_at":"2024-12-09 16:18:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2456668,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4528430/v1/89096cf9-dbbf-44dc-b116-c9799bdc4c43.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Value of intraoperative post-conisation human papillomavirus testing in predicting residual or recurrence after treatment with a loop electrosurgical excision procedure in women with HR-HPV positive and cervical high-grade squamous intraepithelial lesion","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHigh-grade squamous intraepithelial lesion (HSIL) of the cervix is caused by persistent high-risk human papillomavirus (HPV) infection[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], and is a precursor of cervical cancer. Surgical excision by either cold knife conization, laser conization or loop electrosurgical excision procedure (LEEP) is the gold standard treatment[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, approximately 15% of patients experience varying degrees of residual or recurrence after surgery[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA few studies have evaluated the risk of recurrence after LEEP in women with HSIL, but the results have been inconsistent [\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Age, smoking, lesion size and severity, high-risk human papillomavirus (HR-HPV) type, and persistence of HR-HPV after treatment have each been shown to predict residual or recurrent CIN [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In addition, margin involvement is a well-established risk factor for treatment failure [\u003cspan additionalcitationids=\"CR12 CR13 CR14\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. There is still uncertainty and debate as to which risk factor or combination of factors most accurately predicts recurrence.\u003c/p\u003e \u003cp\u003eIt is known that most precancerous lesions are located in the transformation zone, and that after excision of the transformation zone, a high percentage of women will have clearance not only of the lesion but also of the HPV infection. Therefore, in women undergoing LEEP where the lesion is completely removed, we would expect the HPV test performed intraoperatively immediately after excision (the IOP HPV test) to be negative, and positive if the excision was incomplete.\u003c/p\u003e \u003cp\u003eTherefore, this article attempts to evaluate the feasibility and utility of intraoperative HPV testing (IOP-HPV) performed in the residual cervix immediately after conisation for HSIL, and to determine whether it could be an early marker of disease clearance or persistence. We also analysed the population by age and menopausal status to see if there was a difference in the risk of recurrence.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003eData collection\u003c/h2\u003e\nThis prospective study included 114 patients with HSIL/CIN2-3 who underwent LEEP at the First Affiliated Hospital of Wenzhou Medical University between February 2021 and May 2022. The enrolled patients were all high-risk HPV (HR-HPV) positive and were diagnosed by colposcopically-directed biopsy (CDB) or endocervical curettage (ECC) within 90 days prior to treatment. All women were followed for a minimum of 24 months. Exclusion criteria were the presence of an immunosuppressive disorder and chronic treatment with immunosuppressive drugs, pathology upgraded to cervical cancer after LEEP, or for whom follow-up information was not available. The study was approved by the Institutional Review Board of the First Affiliated Hospital of Wenzhou Medical University (number: KY2020-053). Written informed consent was obtained from all participants.\u003cbr /\u003e\n\u003cp\u003eBefore LEEP, the abnormal area was delineated with acetic acid and Lugol's solution and removed adjacent to the transformation zone, followed by selective coagulation of the surgical bed with a diathermic coagulation ball. Immediately after LEEP, cervical specimens were collected for IOP-HPV testing, cytology and DNA ploidy analysis of cervical exfoliated cells. ECC was performed at the end of the procedure. HPV genotyping was performed on specimens by PCR and flow fluorescence hybridisation. Cytology samples were interpreted by an experienced pathologist according to the Bethesda system[\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]. For DNA ploidy analysis, after Feulgen staining of cervical cells, the samples were scanned by an automated high-resolution cellular DNA image analysis system. The system analysed multiple parameters of each sample nucleus and automatically performed cell counting and classification according to various characteristic parameters.\u003c/p\u003e\n\u003cp\u003eFollow-up visits were scheduled at 6, 12 and 24 months. At each visit, liquid-based cytology (LBC), HPV testing and DNA ploidy analysis of cervical exfoliated cells were performed. Individuals with any of the three abnormalities underwent colposcopic cervical biopsy, and if the conversion zone was not completely visible or no abnormalities were found on colposcopy, ECC was performed. If all were negative, routine colposcopy and cervical biopsy were performed at 6 and 24 months after surgery. Lesions found within 6 months were considered residual, while those found after 6 months were considered recurrent. If HSIL or more severe lesions were found, a second surgical treatment was performed and follow-up was terminated.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003eStatistical methods\u003c/h2\u003e\n\u003cp\u003eIn this study, the included participants were categorized as \"IOP-HPV positive\" and \"IOP-HPV negative\", continuous variables were described as \u0026ldquo;mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (standard deviation)\u0026rdquo;, categorical variables were described as \u0026ldquo;N (%)\u0026rdquo;, and comparisons of differences between the two groups were made using either the Kruskal-Wallis H test or the Chi-square test. We used logistic regression model to assess the association between IOP-HPV and postoperative residual/recurrence. In the analysis we developed three models, model I was unadjusted, model II was adjusted for type of transformation zone, IOP cytology, post-conisation endocervical curettage and model III was adjusted for type of transformation zone, pathology of colposcopy-guided biopsy, IOP cytology, IOP DNA ploidy analysis, cone margin, post-conisation endocervical curettage. Covariates were included as potential confounders in the adjusted models if they changed the estimates of IOP-HPV on postoperative residual/recurrence by more than 10% or were significantly associated with postoperative residual/recurrence. In addition, we performed interaction and stratified analysis by age and menopause in the sensitivity analyses. R language 4.2.1 was used to analyse all data. In all analyses, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eDuring the specified time period, 114 patients met the selection criteria and were included in the study, of whom histological examination of LEEP specimens revealed early cervical cancer (stage IA1/IA2) in 6 (5.26%) cases, of which 21 (18.42%) were lost to follow-up (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The median age of all patients was 43 years, ranging from 25 to 62 years, 21.84% (19/87) were menopausal, and the median follow-up was 25 months (range 6\u0026ndash;33 months). At baseline, all patients were positive for HR-HPV prior to treatment. Recurrence/residual HSIL lesions occurred in 9.20% (8/87) of cases and all of these patients received follow-up treatment. The median time to diagnosis of HSIL after LEEP was 10 months (range 6\u0026ndash;14 months). Of the 8 women who developed HSIL after treatment, seven (26.92%) were positive for IOP-HPV and only one (1.64%) was negative for IOP-HPV (\u0026lt;\u0026thinsp;0.001). The characteristics of all patients are summarised in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\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\u003ePatient characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIOP HPV (-)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIOP HPV (+)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.08\u0026thinsp;\u0026plusmn;\u0026thinsp;9.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.50\u0026thinsp;\u0026plusmn;\u0026thinsp;10.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.180\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.555\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026lt;45\u003c/p\u003e \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37(60.66%)\u003c/p\u003e \u003cp\u003e24(39.34%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(53.85%)\u003c/p\u003e \u003cp\u003e12(46.15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.254\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026lt;50\u003c/p\u003e \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45(73.77%)\u003c/p\u003e \u003cp\u003e16(26.23%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (61.54%)\u003c/p\u003e \u003cp\u003e10 (38.46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMenopause\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePremenopausal\u003c/p\u003e \u003cp\u003ePostmenopausal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52(85.25%)\u003c/p\u003e \u003cp\u003e9 (14.75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (61.54%)\u003c/p\u003e \u003cp\u003e10 (38.46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTransformation zone (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType 1\u003c/p\u003e \u003cp\u003eType 2\u003c/p\u003e \u003cp\u003eType 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29(47.54%) 16(26.23%) 16(26.23%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (15.38%)\u003c/p\u003e \u003cp\u003e8 (30.77%)\u003c/p\u003e \u003cp\u003e14 (53.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative HR-HPV test (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.726\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType 16 or 18 positive\u003c/p\u003e \u003cp\u003eOther HR-HPV positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33(54.10%) 28(45.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (50.00%) 13 (50.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative cytology (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.751\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative ASCUS/LSIL/HSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(31.15%) 42(68.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (34.62%) 17 (65.38%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePathology of colposcopy-guided biopsy (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative/LSIL\u003c/p\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(3.28%) 59(96.72%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(19.23%)\u003c/p\u003e \u003cp\u003e21 (80.77%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative ECC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative/LSIL\u003c/p\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003cp\u003eNot satisfactory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24(39.34%)\u003c/p\u003e \u003cp\u003e18(29.51%) 19(31.15%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (23.08%)\u003c/p\u003e \u003cp\u003e16 (61.54%)\u003c/p\u003e \u003cp\u003e4 (15.38%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIOP/6-months tests\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIOP cytology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003e\u0026ge;ASC-US\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54(88.52%) 7(11.48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (57.69%)\u003c/p\u003e \u003cp\u003e11 (42.31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIOP DNA\u0026nbsp;ploidy\u0026nbsp;analysis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44(72.13%) 17 (27.87%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(42.31%) 15 (57.69%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCone margin\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58(95.08%) 3 (4.92%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17(65.38%) 9 (34.62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePost-conisation ECC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60(98.36%) 1 (1.64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(76.92%) 6 (23.08%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSix-month cytology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003cp\u003eUnavailable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53(86.89%) 0(0.00%) 8 (13.11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(50.00%) 3(11.54%) 10 (38.46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSix-month DNA\u0026nbsp;ploidy\u0026nbsp;analysis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003cp\u003eUnavailable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47(77.05%) 6(9.84%) 8 (13.11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (42.31%)\u003c/p\u003e \u003cp\u003e5 (19.23%)\u003c/p\u003e \u003cp\u003e10 (38.46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSix-month HPV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive Unavailable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46(75.41%) 7(11.48%) 8 (13.11%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (26.92%)\u003c/p\u003e \u003cp\u003e9 (34.62%)\u003c/p\u003e \u003cp\u003e10 (38.46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRecurrence\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eYes\u003c/p\u003e \u003cp\u003eLSIL\u003c/p\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (90.16%)\u003c/p\u003e \u003cp\u003e6(9.84%) 5(8.20%) 1 (1.64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(46.15%) 14(53.85%) 7(26.92%) 7 (26.92%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eFactors associated with residual/recurrence\u003c/h2\u003e \u003cp\u003eUnivariate regression analysis showed the ORs associated with residual/recurrence (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Patients with cervical transformation zones of type 2 (OR\u0026thinsp;=\u0026thinsp;5.00; 95% CI\u0026thinsp;=\u0026thinsp;1.16\u0026ndash;21.51; P\u0026thinsp;=\u0026thinsp;0.0306) and type 3 (OR\u0026thinsp;=\u0026thinsp;4.29; 95% CI\u0026thinsp;=\u0026thinsp;1.04\u0026ndash;17.74; P\u0026thinsp;=\u0026thinsp;0.0446) had a higher risk of residual or recurrent lesions than those with transformation zones of type 1. Interestingly, patients whose colposcopy-guided biopsy pathology was LSIL or negative (i.e., tissue from the cervical curettage was diagnosed as HSIL) had a significantly increased risk of postoperative recurrence compared to those whose colposcopy-guided biopsy pathology was HSIL (OR\u0026thinsp;=\u0026thinsp;0.19; 95% CI\u0026thinsp;=\u0026thinsp;0.04\u0026ndash;0.92; P\u0026thinsp;=\u0026thinsp;0.0396).\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\u003eFactors associated with residual/recurrence.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.01 (0.96, 1.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.7356\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026lt;45\u003c/p\u003e \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e0.93 (0.34, 2.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.8865\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026lt;50\u003c/p\u003e \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e1.01(0.34, 3.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.9898\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMenopause\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePremenopausal\u003c/p\u003e \u003cp\u003ePostmenopausal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e1.78 (0.57, 5.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.3180\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTransformation zone\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType 1\u003c/p\u003e \u003cp\u003eType 2\u003c/p\u003e \u003cp\u003eType 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e5.00 (1.16, 21.51)\u003c/p\u003e \u003cp\u003e4.29 (1.04, 17.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0306\u003c/p\u003e \u003cp\u003e0.0446\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative HR-HPV test\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType 16 or 18 positive\u003c/p\u003e \u003cp\u003eOther HR HPV positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.69 (0.25, 1.89)\u003c/p\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.4681\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative cytology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003eASCUS/LSIL/HSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e0.85 (0.30, 2.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.7588\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePathology of colposcopy-guided biopsy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative/LSIL\u003c/p\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e0.19 (0.04, 0.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0396\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreoperative ECC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative/LSIL\u003c/p\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003cp\u003eNot satisfactory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e1.57 (0.52, 4.77)\u003c/p\u003e \u003cp\u003e0.31 (0.06, 1.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4248\u003c/p\u003e \u003cp\u003e0.1751\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIOP/6-months tests\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIOP-HPV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e10.69 (3.41, 33.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIOP cytology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003e\u0026ge;ASCUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e5.27 (1.71, 16.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIOP DNA\u0026nbsp;ploidy\u0026nbsp;analysis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e3.52 (1.25, 9.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCone margin\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e4.36 (1.22, 15.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0233\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePost-conisation ECC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e28.29 (3.15, 253.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0028\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSix-month cytology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003cp\u003eUnavailable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e8.15 (0.69, 96.97)\u003c/p\u003e \u003cp\u003e1.57 (0.47, 5.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0967\u003c/p\u003e \u003cp\u003e0.4612\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSix-month DNA\u0026nbsp;ploidy\u0026nbsp;analysis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003cp\u003eUnavailable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e6.53 (1.64, 26.06)\u003c/p\u003e \u003cp\u003e2.09 (0.60, 7.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0078\u003c/p\u003e \u003cp\u003e0.2475\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSix-month HPV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003ePositive\u003c/p\u003e \u003cp\u003eUnavailable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003cp\u003e50.00 (9.85, 253.70)\u003c/p\u003e \u003cp\u003e6.41 (1.35, 30.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003cp\u003e0.0193\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFor pathological findings in LEEP specimens, margin involvement was significantly associated with residual/recurrence (P\u0026thinsp;=\u0026thinsp;0.0233), with ORs of 4.36 (95% CI\u0026thinsp;=\u0026thinsp;1.22, 15.55). Similarly, a positive result suggested by endocervical curettage after conisation significantly increased the risk of postoperative recurrence (OR\u0026thinsp;=\u0026thinsp;28.29; 95% CI\u0026thinsp;=\u0026thinsp;3.15\u0026ndash;253.80; P\u0026thinsp;=\u0026thinsp;0.0028). Patients with intraoperative HPV positivity (OR\u0026thinsp;=\u0026thinsp;10.69; 95% CI\u0026thinsp;=\u0026thinsp;3.41\u0026ndash;33.51; P\u0026thinsp;\u0026lt;\u0026thinsp;0.01), cytological abnormalities (OR\u0026thinsp;=\u0026thinsp;5.27; 95% CI\u0026thinsp;=\u0026thinsp;1.71\u0026ndash;16.27; P\u0026thinsp;=\u0026thinsp;0.0038) and DNA ploidy positivity (OR\u0026thinsp;=\u0026thinsp;3.52; 95% CI\u0026thinsp;=\u0026thinsp;1.25\u0026ndash;9.94; P\u0026thinsp;=\u0026thinsp;0.0172) all had a significantly increased risk of postoperative residual/recurrence. Meanwhile, patients with HPV positivity (OR\u0026thinsp;=\u0026thinsp;50; 95% CI\u0026thinsp;=\u0026thinsp;9.85\u0026ndash;253.70; P\u0026thinsp;\u0026lt;\u0026thinsp;0.01) or DNA ploidy positivity (OR\u0026thinsp;=\u0026thinsp;6.53; 95% CI\u0026thinsp;=\u0026thinsp;1.64\u0026ndash;26.06; P\u0026thinsp;=\u0026thinsp;0.0078) at 6 months post-operatively also had a significantly increased risk of recurrence, but unexpectedly, the increased risk in patients with abnormal cytology at 6 months post-operatively was not statistically significant.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e\u003cb\u003eMultifactorial regression analysis of the association between intraoperative HPV positivity and postoperative residual/recurrence\u003c/b\u003e\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the ORs and 95% CIs of the association between intraoperative HPV infection and postoperative residual or recurrent disease in the three regression models. In model I, we found that IOP-HPV positivity was a risk factor for residual or recurrent disease within 2 years of LEEP in women with HSIL (OR\u0026thinsp;=\u0026thinsp;10.69, 95% CI:3.41, 33.51, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Based on these results, further analyses showed that IOP-HPV positive was strongly associated with the occurrence of residual/recurrent LSIL (OR\u0026thinsp;=\u0026thinsp;6.42, 95% CI:1.74, 23.70, P\u0026thinsp;=\u0026thinsp;0.0053) and HSIL (OR\u0026thinsp;=\u0026thinsp;32.08, 95% CI:3.60, 285.64, P\u0026thinsp;=\u0026thinsp;0.0019). More interestingly, the OR was significantly higher in the HSIL group than in the LSIL group (32.08 vs 6.42). In models II and III, the above conclusions remained after adjustment for multiple confounders. IOP-HPV positive showed a robust positive correlation with residual/recurrent cervical lesions.\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\u003eMultifactorial analysis of the association between intraoperative HPV positivity and postoperative residual/recurrence\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel I\u003c/p\u003e \u003cp\u003eOR(95%CI) P-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModel II\u003c/p\u003e \u003cp\u003eOR(95%CI) P-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModel III\u003c/p\u003e \u003cp\u003eOR(95%CI) P-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon- recurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003erecurrence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10.69 (3.41, 33.51)\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6.75 (1.85, 24.59) 0.0038\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.47 (1.94, 28.72) 0.0034\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.42(1.74, 23.70) 0.0053\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.83 (1.17, 19.95) 0.0295\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.22 (1.20, 22.73) 0.0275\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32.08 (3.60, 285.64) 0.0019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16.83 (1.20, 236.37) 0.0362\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e37.52 (1.35, 1045.14) 0.0327\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eModel I adjust for: None\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eModel II adjust for: Type of transformation zone, IOP cytology, Post-conisation endocervical curettage\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eModel III adjust for: Type of transformation zone, Pathology of colposcopy-guided biopsy, IOP cytology, IOP DNA ploidy analysis, Cone margin, Post-conisation endocervical curettage\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStratified associations between IOP-HPV and postoperative residual/recurrent lesion by age and menopause\u003c/h2\u003e \u003cp\u003e We performed further stratified analyses according to the age of the patients and whether they were menopausal or not (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The results showed that there was no significant difference in the risk of postoperative lesion residue/recurrence in patients with IOP HPV positivity, whether they were over or under 45 years of age. In contrast, the risk of postoperative residual/recurrence was significantly higher in patients younger than 50 years than in those older than 50 years. According to models II and III, for patients with IOP-HPV positivity, the risk of postoperative recurrence was 29 times (Interaction-P\u0026thinsp;=\u0026thinsp;0.0096) and 55.9 times (Interaction-P\u0026thinsp;=\u0026thinsp;0.0120) higher for patients younger than 50 years, respectively. In addition, premenopausal patients who were HPV-positive intraoperatively had a significantly higher risk of recurrence or residual lesions found postoperatively than postmenopausal patients. According to model II, in non-menopausal women, IOP-HPV positivity is associated with a risk of postoperative lesion recurrence or residual disease that is approximately 59 times higher than in postmenopausal women (Interaction-P\u0026thinsp;=\u0026thinsp;0.0023). Furthermore, after adjusting for all confounders in model III, the ratio is 130 times higher Interaction-P\u0026thinsp;=\u0026thinsp;0.0027), which is still statistically significant.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis is one of the few studies to evaluate IOP-HPV testing as an early marker for residual/recurrent cervical high-grade squamous intraepithelial lesion. The present study highlights positive IOP-HPV testing as an important risk factor for recurrence. More interestingly, for these HSIL patients with preoperative HR-HPV positivity, we found that if IOP-HPV testing was positive, being younger than 50 years or non-menopausal was associated with a greater risk of residual or recurrent lesions after LEEP (P\u0026lt;0.05).\u003c/p\u003e \u003cp\u003eIt has been reported that approximately 15% of women treated for high-grade cervical intraepithelial neoplasia (CIN grade 2 or 3) develop residual or recurrent CIN grade 2 or 3 or cervical cancer [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], with the majority of these diagnosed within 2 years of treatment [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In our study, all patients included were HR-HPV positive preoperatively and we found that 9.2% of them developed recalcitrant/recurrent disease during the two-year postoperative follow-up period, which is consistent with the findings in previous literature. Because of this significant risk, close follow-up of these patients is standard practice. Several risk factors for recurrence of cervical lesions have been suggested in the literature [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Bogani et al investigated the effect of persistent HPV infection on the risk of CIN2\u0026thinsp;+\u0026thinsp;recurrence in 545 patients undergoing primary conisation [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The results showed that the risk of recurrence in patients with persistent HPV infection 6 months after cervical conization was 7.46%, whereas the risk of recurrence of cervical lesions in patients with persistent HPV infection 12 months after cervical conization was 13.1%. In addition, the results of a multicentre, 5-year follow-up study of recurrence rates after loop electrosurgery and laser conisation showed that HPV persistence was the only factor associated with 5-year recurrence [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFurthermore, in postmenopausal women, persistent infection with the same HR-HPV genotypes, particularly HPV-18, has been shown to be a risk factor for the development of recurrent CIN2-3 [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Therefore, postoperative HPV infection is considered an important risk factor for HSIL recurrence and is now an important test recommended for postoperative follow-up in clinical practice.\u003c/p\u003e \u003cp\u003eHowever, early identification of patients at higher risk of treatment failure may help to avoid delays in retreatment of these patients and reduce unnecessary visits by women at very low risk of developing the disease. A pilot study by Torne et al was the first to demonstrate that IOP-HPV testing is feasible and accurately predicts treatment failure in patients with CIN2-3. Specifically, treatment failure was found in 12/132 women (9.1%) in the study. The sensitivity, specificity, positive predictive value, and negative predictive value of IOP-HPV testing for treatment failure were superior to other conventional predictors (cone margins, endocervical smears, and 6-month intraoperative cytology), and on multivariate analysis, IOP-HPV was highly associated with treatment failure (OR15.40, 95% CI 1.58-150.42)[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. J Rabasa etal performed a similar study to evaluate whether the IOP-HPV test has the same prognostic value as the HPV test performed 6 months after treatment for HSIL to predict treatment failure. They found that the recurrence rate of HSIL was 6%. There was a strong association between a positive IOP-HPV test, a positive 6-month HPV test, a positive HPV 16 genotype, positive surgical margins and HSIL recurrence. The sensitivity, specificity, and positive and negative predictive values of the IOP-HPV test were better than those of the HPV test at 6 months[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Therefore, they believe that this new approach may allow early identification of patients with recurrent disease, which will not delay treatment. Genotyping could be useful in identifying high-risk patients. However, the study was only followed up to 12 months post-surgery and to remedy this, the team subsequently published the results of a 24-month follow-up study showing that the recurrence rate of HSIL was 6.2% (19/304). HPV testing after loop electrosurgical resection predicted HSIL recurrence at 24 months with similar diagnostic accuracy to HPV testing at 6 months. The direct economic savings after the provisional suppression of procedures included in the 6-month control assessment per patient with high-grade intraepithelial lesion was estimated to be 172.8 \u0026euro;[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. These studies aroused our intense interest and our results showed similar rates of postoperative recurrence and validated IOP-HPV as an important risk factor for postoperative recurrence. However, among patients with IOP-HPV positivity, is there a difference in the risk of postoperative recurrence according to age or menopausal status? To my knowledge, no relevant study has investigated this question.\u003c/p\u003e \u003cp\u003eMenopause has been suggested to be associated with persistent HPV infection. Results from a retrospective cohort study by So KA etal showed that older age (\u0026gt;\u0026thinsp;50 years) and menopause were associated with persistent HR-HPV infection after cervical conization, and multifactorial analyses showed that menopausal status was the only significant independent predictor of HR-HPV persistence after treatment[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. However, a study aimed at analysing the characteristics of HPV distribution, prevalence of infection and age risk in premenopausal and postmenopausal women showed that menopause was not associated with HPV infection[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In addition, a previous study of HPV infection in 20,000 women from nine provinces in China showed that the prevalence of HR-HPV infection in more than 2,000 postmenopausal women (17.2%) was not significantly different from that in non-menopausal women (16.4%) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIt is controversial whether menopause increases a patient's risk of HPV infection. It is also inconclusive whether menopause is associated with recurrence after HSIL treatment. The results of a Korean study showed that menopause (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; OR, 3.969), pre- and post-operative HR-HPV load (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05; OR, 2.430; P\u0026thinsp;\u0026lt;\u0026thinsp;0.05; OR, 5.351), and infection with multiple HR-HPV types (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05; OR (2.345) were significantly associated with residual/recurrent CIN after surgery [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. However, Gosvig CF et al. found that persistent HR-HPV infection after cervical conization was not associated with age[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], and the findings of Amal M.A et al. also demonstrated that age and menopause were not associated with postoperative recurrence of HSIL[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. This is similar to previously reported studies[\u003cspan additionalcitationids=\"CR36\" citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, the population was all preoperatively HR-HPV positive and pathologically diagnosed with HSIL. We were surprised to find that among them, IOP-HPV positivity at age less than 50 years or premenopausal was more significantly associated with residual/recurrent lesions (including HSIL and LSIL). This observation may be related to more frequent sexual intercourse before age 50 or before menopause. What's more, postmenopausal women were more likely to have cervical adhesions and strictures after LEEP, making it difficult to diagnose recurrent lesions. This needs to be confirmed and investigated in studies with large samples. By identifying the risk factors for HSIL recurrence and residual disease, the best and most precise way to treat HSIL and IOP-HPV positive patients will be explored.\u003c/p\u003e \u003cp\u003eThis study is one of the few to use intraoperative HPV testing as an early predictor of residual or recurrent cervical HSIL. Our study was performed by the same surgeon to ensure consistency of surgery. There are still some shortcomings of this study. The sample size is small, which may cause some variability in the research results. The follow-up study is expected to address these shortcomings and provide a more in-depth discussion.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe rate of residual or recurrent lesions after LEEP treatment for HSIL was approximately 9.2%. IOP-HPV positivity was an independent risk factor for residual or recurrent HSIL. In addition, IOP-HPV positivity, age less than 50 years, or premenopausal status were more significantly associated with residual or recurrent lesions. Therefore, IOP-HPV testing for LEEP may have significant clinical value in the early prediction of residual or recurrent high-grade squamous intraepithelial lesions of the cervix, allowing for personalised management and timely follow-up. Larger studies are needed to confirm whether IOP-HPV testing can replace or complement traditional follow-up strategies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eASCUS \u0026nbsp;Atypical squamous cells of undetermined signifcance\u003c/p\u003e\n\u003cp\u003eCDB \u0026nbsp; \u0026nbsp;Colposcopically directed biopsy\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCIN \u0026nbsp; \u0026nbsp; \u0026nbsp;Cervical intraepithelialneoplasia\u003c/p\u003e\n\u003cp\u003eECC \u0026nbsp; \u0026nbsp; Endocervical curettage\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHR-HPV \u0026nbsp;High-risk human papillomavirus\u003c/p\u003e\n\u003cp\u003eHSIL \u0026nbsp; \u0026nbsp; High-grade squamous intraepithelial lesion\u003c/p\u003e\n\u003cp\u003eIOP-HPV \u0026nbsp;Intraoperative post-conisation human papillomavirus\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLBC \u0026nbsp; \u0026nbsp; Liquid-based cytology\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTCT \u0026nbsp; \u0026nbsp; \u0026nbsp;ThinPrep cytologic test\u003c/p\u003e\n\u003cp\u003eLEEP \u0026nbsp; \u0026nbsp; Loop electrosurgical excisional procedure\u003c/p\u003e\n\u003cp\u003eLSIL \u0026nbsp; \u0026nbsp; \u0026nbsp;Low-grade squamous intraepithelial lesion\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e\u0026rsquo;\u003c/strong\u003e\u003cstrong\u003econtributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWX and XL had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of data analysis. Conception and design: WX, XL and SD.Acquisition, analysis, or interpretation of data: WX, SY, CC, and XL. Drafting of the manuscript: WX, YH, and XL. Critical revision of the manuscript for important intellectual content: WX, SD and XL. Statistical analysis: WX, XL,CC. Data Collection: SD, SY, and XL.Supervision: YH. All authors read and approved the fnal manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eScientific and Technology Project of Wenzhou (grant number Y20210369)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analysed during the current study are not publicly available due avoid unreasonable use by third parties or organizations, but are \u0026nbsp;available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University. Informed consent was obtained for all patients or family members. In addition, all methods were performed in accordance with the relevant guidelines and regulations.\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\u003eCompeting interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWalboomers JMM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189(1):12\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartin-Hirsch PP, Paraskevaidis E, Bryant A, Dickinson HO, Keep SL. Surgery for cervical intraepithelial neoplasia. Martin-Hirsch PP, editor. 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JAMA. 2002;287(16):2114\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZielinski GD, Bais AF, Helmerhorst TJM, Ren\u0026eacute; HM, Verheijen, Frits, Peter JF, Snijders, et al. HPV Testing and Monitoring of Women After Treatment of CIN 3: Review of the Literature and Meta-analysis. Obstet Gynecol Surv. 2004;59(7):543\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMelnikow J, McGahan C, Sawaya GF, Ehlen T, Coldman A. Cervical Intraepithelial Neoplasia Outcomes After Treatment: Long-term Follow-up From the British Columbia Cohort Study. JNCI J Natl Cancer Inst. 2009;101(10):721\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBogani G, DI Donato V, Sopracordevole F, Ciavattini A, Ghelardi A, Lopez S, et al. Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser Conization: A 5-year follow-up study. 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BMC Women\u0026rsquo;s Health. 2021;21(1).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolt HK, Zhang L, Zhao FH, Hu SY, Zhao XL, Zhang X, et al. Evaluation of multiple primary and combination screening strategies in postmenopausal women for detection of cervical cancer in China. Int J Cancer. 2016;140(3):544\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOuh YT, Cho HW, Kim SM, Min KJ, Lee SH, Song JY, et al. Risk factors for type-specific persistence of high-risk human papillomavirus and residual/recurrent cervical intraepithelial neoplasia after surgical treatment. Obstet Gynecol Sci. 2020;63(5):631\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGosvig CF, Huusom LD, Andersen KK, Iftner A, Cederkvist L, Svare E, et al. Persistence and reappearance of high-risk human papillomavirus after conization. Gynecol Oncol. 2013;131(3):661\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbdulaziz AMA, You X, Liu L, Sun Y, Zhang J, Sun S, et al. Management of high-grade squamous intraepithelial lesion patients with positive margin after LEEP conization. Medicine. 2021;100(20):e26030.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen J, Wang Z, Wang Z, Yang X. The risk factors of residual lesions and recurrence of the high-grade cervical intraepithelial lesions (HSIL) patients with positive-margin after conization. Medicine. 2018;97(41):e12792.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeguevaque P, Motton S, Decharme A, Soul\u0026eacute;-Tholy M, Escourrou G, Hoff J. Predictors of recurrence in high-grade cervical lesions and a plan of management. Eur J Surg Oncol. 2010;36(11):1073\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark JY, Lee KH, Dong SM, Kang S, Park SY, Seo SS. The association of pre-conization high-risk HPV load and the persistence of HPV infection and persistence/recurrence of cervical intraepithelial neoplasia after conization. Gynecol Oncol. 2008;108(3):549\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"HSIL, LEEP, IOP-HPV, recurrence, residual","lastPublishedDoi":"10.21203/rs.3.rs-4528430/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4528430/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo evaluate the feasibility of intraoperative human papillomavirus (IOP-HPV) testing for the prediction of postoperative treatment failure in patients with high-grade squamous intraepithelial lesion (HSIL) undergoing loop electrosurgical excisional procedure (LEEP)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 114 women diagnosed with HSIL by biopsy and/or endocervical curettage who underwent LEEP were included in a prospective cohort study. IOP-HPV testing was performed immediately after the procedure. Patients were followed up for 24 months. Logistic regression was used to analyse the factors influencing the residual or recurrent lesions. Further stratified analyses were performed to investigate the differences in prognosis of IOP-HPV positivity in patients of different age and menopausal status.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1. Of the 114 patients, 6 (5.26%) were pathologically upgraded to cervical cancer, and 21 (18.42%) were lost to follow-up. Recurrence or residual HSIL lesions occurred in 9.20% (8/87) of cases. Of the 8 women who developed post-treatment HSIL, 7 (26.92%) were positive for IOP-HPV, and only 1 (1.64%) was negative for IOP-HPV (\u0026lt;0.01).\u003c/p\u003e\n\u003cp\u003e2. Transformation zones of type 2 (P =0.0306) or type 3 (P =0.0446) , diagnosed as LSIL/negative by cervical biopsy (P=0.0396), margin involvement (P=0.0233), positive endocervical curettage after conisation (P=0.0028), intraoperative HPV (P \u0026lt;0.01), cytological abnormalities (P=0.0038), DNA ploidy (P =0.0172), and postoperative HPV (P \u0026lt;0.01) and DNA ploidy (P=0.0078) positivity at 6 months were associated with a higher risk of residual or recurrent lesions.\u003c/p\u003e\n\u003cp\u003e3. The results of the multivariate regression analysis showed that IOP-HPV positivity was the independent risk factor for residual or recurrent lesions (OR=10.69 , 95% CI:3.41, 33.51, P\u0026lt;0.01). IOP-HPV positivity was strongly associated with the occurrence of residual/recurrent LSIL (OR=6.42 , 95% CI:1.74, 23.70, P=0.0053) and HSIL (OR=32.08 , 95% CI:3.60, 285.64, P=0.0019).\u003c/p\u003e\n\u003cp\u003e4. Stratified analyses showed that IOP-HPV positive in patients younger than 50 years or premenopausal patients was associated with a significantly higher risk of recurrence or residual lesions (p\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIOP-HPV positivity is an independent risk factor for residual or recurrent HSIL lesions. In addition, IOP-HPV positivity was more associated with residual or recurrent lesions in those younger than 50 years or premenopausal. IOP-HPV testing may be of critical clinical value in providing the early and accurate prediction of residual or recurrent lesions.\u003c/p\u003e","manuscriptTitle":"Value of intraoperative post-conisation human papillomavirus testing in predicting residual or recurrence after treatment with a loop electrosurgical excision procedure in women with HR-HPV positive and cervical high-grade squamous intraepithelial lesion","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-25 20:15:42","doi":"10.21203/rs.3.rs-4528430/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-30T18:53:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-30T15:49:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"158646684911392160701789296480968137268","date":"2024-10-20T13:32:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"303093728208583749757995334192026110299","date":"2024-06-27T08:44:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-21T23:03:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"85634508829776539698600915830875308004","date":"2024-06-16T19:23:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-12T17:09:11+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-06-06T18:27:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-05T23:59:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-05T23:58:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2024-06-04T13:32:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3b5a6bb2-ae01-4dc8-b1dc-694567781fe5","owner":[],"postedDate":"June 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-09T16:13:09+00:00","versionOfRecord":{"articleIdentity":"rs-4528430","link":"https://doi.org/10.1186/s12885-024-13272-9","journal":{"identity":"bmc-cancer","isVorOnly":false,"title":"BMC Cancer"},"publishedOn":"2024-12-05 15:58:08","publishedOnDateReadable":"December 5th, 2024"},"versionCreatedAt":"2024-06-25 20:15:42","video":"","vorDoi":"10.1186/s12885-024-13272-9","vorDoiUrl":"https://doi.org/10.1186/s12885-024-13272-9","workflowStages":[]},"version":"v1","identity":"rs-4528430","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4528430","identity":"rs-4528430","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}