HPV vaccination following cervical intraepithelial neoplasia grade 2 diagnosis and risk of progression

Human papillomavirus (HPV) vaccination is associated with a significantly reduced risk of cervical cancer when administered before initial exposure to HPV. Women with high-grade cervical intraepithelial neoplasia (CIN) have an increased risk of subsequent HPV-related disease, including recurrent high-grade CIN, compared to women without CIN. Some clinicians have advised women with high-grade CIN to undergo HPV vaccination to reduce their subsequent risk, despite a lack of evidence for this practice. We aimed to evaluate whether HPV vaccination of women undergoing active surveillance for CIN grade 2 (CIN2) is associated with a decreased risk of progression to cervical intraepithelial neoplasia grade 3 or worse (CIN3+).

We conducted a nationwide population-based historical cohort study in Denmark on women aged 18-40 years undergoing active surveillance for CIN2 from 2007 to 2020. We compared women receiving at least one HPV vaccine dose within 6 months after their CIN2 diagnosis to women not receiving the vaccine. Our primary outcome was progression to CIN3+. We stratified by age at CIN2 diagnosis (18-29, 30-40), calendar year (2007-2012, 2013-2020), and index cytology (high-grade, nonhigh-grade). We used Cox proportional hazards regression to estimate hazard ratios of the outcomes with unvaccinated women as the reference. Age at diagnosis, calendar year, index cytology, income, and educational level were adjusted for.

We included 4585 women, of whom 583 (12.7%) were vaccinated within 6 months after CIN2 diagnosis. A total of 1391 (30.3%) progressed to CIN3+ during follow-up. The 5-year cumulative risk was 29.9% (28.5-31.3). Overall, no protective effect of vaccination after CIN2 diagnosis was found (aHR 1.45 [1.24-1.69]). Stratified analyses showed increased progression risk with vaccination among women <30 years, in the early calendar period (2007-2012), and across both non-high-grade and high-grade index cytology; no significant difference in risk was observed in women ≥30 years or in the latest calendar period (2013-2020).

HPV vaccination did not reduce the risk of progression in women undergoing active surveillance for CIN2. This finding indicates that HPV vaccination should not be recommended in this group of women.