CIN2 and Active Surveillance: Evidence from 48-Month Follow-Up in an HPV-Positive Cohort

Background: Conservative management of grade 2 cervical intraepithelial neoplasia (CIN2) is now supported by international guidelines, especially in young women or those seeking fertility. However, identifying subgroups at increased risk of progression remains a clinical priority, especially in settings with prolonged surveillance. Objectives: To evaluate the clinical evolution of CIN2 in an HPV-positive cohort followed under active surveillance for a maximum follow-up of 48 months, with particular attention to the risk of progression, persistence and regression, and associated predictors. Methods: Retrospective observational study conducted on a cohort of 237 HPV-positive women with a histological diagnosis of CIN2. Three possible clinical outcomes (progression, persistence, and regression) were analyzed. Patients underwent structured follow-up including cytology and colposcopy every 6 months, and HPV testing annually. Excisional treatment was performed only in case of progression or poor compliance. Logistic regression (univariate and multivariate) was applied to identify independent predictors of progression and regression. Results: After a maximum follow-up of 48 months. 61.3% of lesions regressed spontaneously, 13.1% persisted, and 25.5% progressed to CIN3. In multivariate analysis, high-grade cytology (ASC-H/HSIL) and HPV 16/18 infection were independently associated with a reduced likelihood of regression (OR ≈ 0.5, p < 0.01) and an increased risk of progression (OR ≈ 2.0, p < 0.05). Lesion size and age were not significant predictors. Importantly, no invasive carcinoma occurred during follow-up. Conclusions: Active surveillance for CIN2 remains a valid strategy in low-risk subgroups, but it is not universally safe. Data suggest that the combination of high-grade cytology and HPV 16/18 represents a high oncological risk profile, for which prompt treatment is indicated. Persistence beyond 36 months should be considered a cumulative risk marker, with implications for personalized follow-up and risk management. Further prospective, registry-linked studies are required to validate long-term safety and refine risk-based management strategies for CIN2.