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Risk-stratified surveillance after LEEP: a nomogram integrating HPV persistence, margin status, and clinical factors
Haixia Shang1, Xiaofeng Shi1, Hongxin Yu2
1Department of Obstetrics and Gynecology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, China.
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 modeling. 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 one-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.
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