The study examined risk factors for disease progression in 510 women with CIN2 undergoing active surveillance from January 2012 to March 2021. During a median follow-up of 37 months, 65.9% (336 patients) achieved complete regression, 10.8% (55 patients) persisted, and 23.3% (119 patients) progressed. Multivariate analysis identified HPV16 infection (OR 4.07, 95% CI 1.88–8.81) and more than three pregnancies (OR 4.38, 95% CI 1.63–11.79) as independent risk factors for progression. HPV vaccination given after CIN2 diagnosis was an independent protective factor (OR 0.29, 95% CI 0.08–0.98). The estimated 5-year Kaplan-Meier progression rate was 72% (5 of 13 patients) in the high-risk subgroup (unvaccinated, HPV16-positive women with more than three pregnancies) versus 7.6% (27 of 497 patients) in the low-risk subgroup. The authors recommend risk stratification by HPV16 status and pregnancy history and strongly suggest vaccination after CIN2 diagnosis to reduce the risk of progression.