HPV16/18 Genotyping Combined with PAX1 Methylation Triage Reduces Unnecessary Colposcopy While Improving CIN3+ Detection: A Real-World Study of 3,253 Chinese Women

HPV16/18 Genotyping Combined with PAX1 Methylation Triage Reduces Unnecessary Colposcopy While Improving CIN3+ Detection: A Real-World Study of 3,253 Chinese Women | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 18 December 2025 V1 Latest version Share on HPV16/18 Genotyping Combined with PAX1 Methylation Triage Reduces Unnecessary Colposcopy While Improving CIN3+ Detection: A Real-World Study of 3,253 Chinese Women Authors : Xing Fan , Haichun Guo , Sifeng Wang , and Xiangwen Peng 0000-0001-9110-5163 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.176603959.96579141/v1 143 views 102 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background : Current cervical cancer screening guidelines recommend colposcopy referral for women co-positive for high-risk human papillomavirus (hrHPV) and abnormal cytology (≥ASC-US). However, cytology exhibits suboptimal sensitivity, and this strategy leads to high colposcopy burdens, especially in populations where non-HPV16/18 genotypes predominate. We evaluated a novel triage strategy using HPV16/18 genotyping and PAX1 methylation to optimize resource allocation. Methods : In a cohort of 3,253 hrHPV-positive women who underwent HPV genotyping, liquid-based cytology (TCT), PAX1 methylation testing, colposcopy, and histopathological confirmation, we compared two strategies: (A) standard referral (hrHPV+ & TCT ≥ ASC-US); (B) novel referral (HPV16/18+ → immediate colposcopy; non-16/18 hrHPV+ → colposcopy if PAX1 methylation ΔCt ≤ 8.79). CIN3+ (CIN3 or cancer) served as the clinical endpoint. Results : Non-16/18 hrHPV types (especially HPV52/58) accounted for over 30% of infections and 60% of CIN2+ lesions. PAX1 methylation was strongly associated with lesion severity (median ΔCt: chronic cervicitis 17.92 vs. CIN3 7.36 vs. cancer 5.97; P < 0.001) and predicted CIN3+ with high accuracy (AUC = 0.82 in non-16/18 group). Strategy B detected 40 additional CIN3+ cases (+30.5%) , reduced colposcopy referrals by 853 cases (absolute −25%, relative −46%) , and increased the positive predictive value (PPV) from 6.6% to 14.6% (2.2-fold improvement) compared to Strategy A. Conclusion : A triage algorithm combining HPV16/18 genotyping with PAX1 methylation significantly enhances CIN3+ detection while substantially reducing unnecessary colposcopies. This strategy is particularly well-suited for Chinese and other Asian populations where non-16/18 hrHPV types are prevalent, offering a more precise, cost-effective approach toward WHO’s 2030 cervical cancer elimination goals. Supplementary Material File (hpv pax.pptx) Download 665.46 KB File (hpv-manuscript file.docx) Download 64.33 KB File (table1.xlsx) Download 8.74 KB File (table2.xlsx) Download 8.91 KB Information & Authors Information Version history V1 Version 1 18 December 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords cancer: trophoblastic disease epidemiology Authors Affiliations Xing Fan Changsha Hospital of Hunan Normal University View all articles by this author Haichun Guo Changsha Hospital of Hunan Normal University View all articles by this author Sifeng Wang Changsha Hospital of Hunan Normal University View all articles by this author Xiangwen Peng 0000-0001-9110-5163 [email protected] Changsha Hospital of Hunan Normal University View all articles by this author Metrics & Citations Metrics Article Usage 143 views 102 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Xing Fan, Haichun Guo, Sifeng Wang, et al. HPV16/18 Genotyping Combined with PAX1 Methylation Triage Reduces Unnecessary Colposcopy While Improving CIN3+ Detection: A Real-World Study of 3,253 Chinese Women. Authorea . 18 December 2025. 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