ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gynecological Oncology
This article is part of the Research TopicSquamous Cell Carcinomas – HPV, or No HPV, That Is The QuestionView all 8 articles
Risk-Stratified Surveillance After LEEP: A Nomogram Integrating HPV Persistence, Margin Status, and Clinical Factors to Predict CIN2+ Recurrence
Provisionally accepted
- Third Hospital of Shanxi Medical University, Taiyuan, China
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Background: Cervical intraepithelial neoplasia (CIN) recurrence after loop electrosurgical excision procedure (LEEP) remains a clinically consequential barrier to cervical cancer prevention, and risk stratification tools tailored to real-world practice are limited in China. This study developed and internally validated a clinical prediction nomogram for histologically confirmed CIN2+ recurrence after LEEP. Methods: A retrospective single-center cohort was assembled of women treated with LEEP for CIN2+ between January 2018 and October 2024. Candidate predictors included demographic and reproductive factors, smoking, HPV vaccination, prior cervical treatment, transformation zone type, LEEP pathology (including adenocarcinoma in situ [AIS] and margin status), pre-/post-treatment high-risk HPV measures, and neutrophil-to-lymphocyte ratio (NLR). Time-to-recurrence was analyzed using Cox regression with hierarchical domain modelling. A nomogram was constructed from the final multivariable model and evaluated for discrimination and calibration. Results: Among 2,230 women (median follow-up 31.8 months, IQR 19.6–43.5), 334 developed CIN2+ recurrence (15.0%), with a median time to recurrence of 15.6 months (IQR 8.2–24.3). Persistent HPV infection occurred in 50.6% of women with recurrence versus 23.1% without recurrence (p<0.001). Persistent HPV infection (same genotype pre-/post-LEEP) was the strongest independent predictor (adjusted hazard ratio [aHR] 2.51, 95% CI 1.99–3.16). Additional independent predictors included unvaccinated status (aHR 1.54, 95% CI 1.08–2.20), multiple positive margins (aHR 1.52, 95% CI 1.08–2.14), AIS versus CIN2 (aHR 1.48, 95% CI 1.03–2.12), prior cervical treatment (aHR 1.38, 95% CI 1.04–1.84), single positive margin (aHR 1.38, 95% CI 1.02–1.87), and higher NLR (per 1-unit increase: aHR 1.21, 95% CI 1.02–1.44). Model discrimination increased across hierarchical models from 0.516 (Model 1) and 0.562 (Model 3) to 0.619 in the final model. Risk stratification separated low-, intermediate-, and high-risk groups with observed 24-month recurrence rates of 6.2%, 14.8%, and 31.5%, respectively (p for trend <0.001). Conclusion: In a contemporary Chinese single-center cohort, genotype-defined persistent HPV infection and margin burden were dominant determinants of CIN2+ recurrence after LEEP, with vaccination status and NLR providing additional stratification. The resulting nomogram offers a pragmatic framework for risk-adapted surveillance, pending external multicenter validation.
Keywords: Cervical Intraepithelial Neoplasia, Loop electrosurgical excision procedure, nomogram, Persistent High-Risk HPV, recurrentCIN2+, surgical margin status
Received: 12 Jan 2026; Accepted: 04 Feb 2026.
Copyright: © 2026 Shang, Shi, Yu, Feng, Huang, Guo, Guo, Guo, Wang and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jingfen Sun
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