# Integrating active surveillance and HPV vaccination for high-risk CIN2: a strategy to reduce disease progression

## TL;DR

This study shows that HPV vaccination after a CIN2 diagnosis can significantly reduce disease progression, especially in high-risk women.

## Contribution

The novel finding is that HPV vaccination administered after CIN2 diagnosis is an effective protective measure against disease progression.

## Key findings

- 65.9% of women with CIN2 undergoing active surveillance achieved complete regression.
- HPV16 infection and more than three pregnancies are independent risk factors for disease progression.
- HPV vaccination after CIN2 diagnosis significantly reduces progression risk (OR 0.29).

## Abstract

This study aimed to identify risk factors associated with disease progression in women with cervical intraepithelial neoplasia grade 2 (CIN2) undergoing active surveillance and to evaluate the protective effect of human papillomavirus (HPV) vaccination administered after diagnosis.

This single-center, retrospective cohort study included 510 women (mean age 30.15 ± 5.82 years, range 18–61) with histologically confirmed CIN2 who chose active surveillance between January 2012 and March 2021. Patient demographics, clinical characteristics, and HPV vaccination status were collected and analyzed. Primary and secondary outcomes were complete regression, persistence, and progression of disease (to CIN3, adenocarcinoma in situ [AIS], or invasive cancer). Univariate and multivariate logistic regression analyses, along with Cox proportional hazards models, were applied to assess risk factors.

Over a mean follow-up period of 37.0 months, 65.9% (336 of 510) of patients achieved complete regression, 10.8% (55 of 510) exhibited persistent CIN2, and 6.3% (32 of 510) experienced disease progression. A multivariate analysis identified HPV16 infection (OR 4.07, 95%CI 1.88–8.81) and having more than three pregnancies (OR 4.38, 95%CI 1.63–11.79) as independent risk factors for progression. Notably, HPV vaccination administered after CIN2 diagnosis was found to be an independent protective factor (OR 0.29, 95%CI 0.08–0.98). The Kaplan–Meier estimated 5-year progression rate was 72% (5 of 13 patients) in the high-risk subgroup (unvaccinated, HPV16-positive women with more than three pregnancies), compared with only 7.6% (27 of 497 patients) in the low-risk subgroup (vaccinated, HPV16-negative women with three or fewer pregnancies).

Active surveillance is a safe and effective management strategy for the majority of women with CIN2. Risk stratification using HPV16 infection status and pregnancy history is crucial for personalized management. HPV vaccination after CIN2 diagnosis is strongly recommended, as it significantly reduces the risk of disease progression.