Lower incidence of vaginal cancer after cervical human papillomavirus screening - long-term follow-up of Finnish randomized screening trial

Objective: Around 70% of vaginal cancers and 40–50% of vulvar cancers are attributable to human papillomavirus (HPV). Globally the burden of these diseases is estimated to grow due to the increasing HPV prevalence and rapidly aging global population. We aimed to examine if HPV screening for cervical cancer has an additional beneficial effect in preventing vaginal and vulvar cancers. To assess this, we used long-term follow-up data from the Finnish randomized HPV screening trial. Methods: Between 2003 and 2008, over 236,000 women were individually randomized (1:1) to primary HPV or cytology screening in Southern Finland. We followed this cohort up to the year 2020. To compare the study arms, we calculated site-specific and pooled incidence rate ratios (IRRs) and mortality rate ratios (MRRs) for vaginal and vulvar cancers using Poisson regression. Results: During 3,5 million person-years of follow-up, the IRR for vaginal cancer in the HPV arm compared to the cytology arm was 0.40 (95% CI 0.17–0.88) and the corresponding MRR was 0.74 (95% 0.21–2.24). The corresponding IRR for vulvar cancer was 0.73 (95% 0.50–1.08) and the MRR was 0.64 (95% 0.23–1.62). The pooled IRR was 0.67 (95% 0.47 ̶ 0.95) and MRR 0.67 (95% 0.31 ̶ 1.37). Conclusion: We found lower incidence of vaginal cancers with HPV screening compared to cytology screening. To validate our results, we recommend analyzing data on vaginal and vulvar cancers also from other HPV screening studies.