Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grade 2+ from childhood vaccinated women: The Trial23 cohort study
The introduction of prophylactic HPV vaccination has significantly reduced vaccine-type HPV infections and is reshaping the landscape of cervical cancer prevention. As vaccinated cohorts enter screening age, understanding the genotype-specific risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) is critical for adapting screening strategies. To compare HPV genotype-specific detection rates of histologically confirmed CIN2+ between vaccinated and unvaccinated women in Denmark's Trial23 cohort, with over seven years of follow-up. This population-based cohort study included 15,668 women born in 1994 who were offered HPV vaccination with the 4-valent vaccine in 2008 and entered Danish screening age in 2017 In our cohort, 95 % were vaccinated and 5 % were unvaccinated. The primary endpoints of this study were HPV-type-specific incident CIN2+ cases. The first histological biopsy sample diagnosed with CIN2+ in 2017-2023 was retrieved for HPV genotyping with the Seegene Allplex HPV28. Cox proportional hazards models estimated hazard ratios (HRs) for CIN2+ outcomes by hierarchically grouped HPV genotypes. Among vaccinated women, the incidence of CIN2+ was 5.3 per 1000 person-years, compared to 12.1 per 1000 person-years in unvaccinated women (HR: 0.44; 95 % CI: 0.34-0.57). Vaccination was associated with a 95 % reduction in HPV16/18-related CIN2+ (HR: 0.05; 95 % CI: 0.03-0.09). A similar, but non-significant, trend of a 32 % risk of CIN2+ for HPV31/33/45/52/58 was found, with an adjusted HR of 0.68 (95 % CI: 0.43-1.09). For CIN2+ associated with other high-risk HPV types, the HR was 0.70 (95 % CI 0.35-1.37). HPV16/18 vaccination reduced the risk of HPV16/18-related CIN2+ lesions, but a substantial burden remained from non-vaccine high-risk types. The substantial protection against HPV16/18-related CIN2+ and the consequential shift in HPV genotype distribution of CIN2+ among vaccinated women underline the need for adaptation of screening strategies.