Journal Article

Is active surveillance of CIN2 always appropriate? Clinical outcomes and factors associated with progression and regression over 48 months in an HPV-positive cohort

Bruno, Maria Teresa, Cavallaro, Antonino Giovanni, Tarascio, Mattia, Panella, Marco Marzio, Pivetti, Elena, Aiello, Tiziana, Pagana, Alessia, Valenti, Gaetano

2026

Overview

Active surveillance of cervical intraepithelial neoplasia grade 2 (CIN2) is increasingly adopted to reduce the risk of overtreatment, particularly in young women. However, the appropriateness of this approach remains debated, especially in light of evidence suggesting an increased long-term risk of cervical cancer in certain subpopulations. A retrospective cohort study was conducted on HPV-positive women with histologically confirmed p16-positive CIN2 managed with active surveillance. Medium-term clinical outcomes included regression, persistence, and progression to CIN3 or higher during follow-up. Survival analyses (Kaplan-Meier), Cox regression models, and Modified Poisson regression models with robust standard errors were performed to identify independent factors associated with progression. The mean follow-up was 27 months, with a maximum follow-up of 48 months. During the observation period, spontaneous regression was observed in 61% of cases, while 25.5% of patients showed progression and 13.8% persistence of the lesion. Regression occurred predominantly within the first 24-36 months, followed by a plateau in the curves. Progression was significantly associated with high-grade cytology (ASC-H/HSIL) and HPV16/18 positivity. In multivariable models, both factors remained independent factors associated with progression, whereas non-16/18 HPV genotypes and low-grade cytology were associated with a higher likelihood of regression. Although this study does not allow for a direct assessment of long-term cancer risk, the identification of early factors associated with persistence and progression provides clinically relevant insights into CIN2 profiles associated with an increased risk of progression within the observed follow-up period. These findings suggest that active surveillance of CIN2 may not be equally appropriate across all patient subgroups and requires careful risk stratification based on virological and cytological factors to support selective and clinically sound management.