HPV vaccination and anal high-grade precancerous lesions and cancer: a real-world effectiveness study

Human papillomavirus (HPV) vaccination has shown high efficacy against anal HPV infection and lesions in clinical trials, and the HPV prevalence and type distribution in anal precancers and cancer predict a high preventable potential for HPV vaccination. However, the real-world effectiveness of HPV vaccination against anal high-grade lesions and cancer is yet to be shown.We investigated HPV vaccine effectiveness against anal high-grade squamous intraepithelial lesion or worse (HSIL+) in a nationwide cohort including all Danish women aged (17-32 years) during October 2006-December 2021 (N = 968,881). HPV vaccinations and first occurrence of anal HSIL+ were retrieved from nationwide registries. Women were considered vaccinated after first dose and classified by age at vaccination. Using Cox regression, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for anal HSIL+ according to vaccination status.During follow-up, the number of incident histological anal HSIL+ cases was 37 in unvaccinated women, and <5 and 26 in women vaccinated at < 17 years and 17-32 years of age, respectively. The overall number of cancers was <5. Compared with unvaccinated women, the risk of histological anal HSIL+ was reduced for women vaccinated at age <17 years (HR = 0.30, 95% CI: 0.10-0.87). For women vaccinated at 17-32 years, the hazard rate of anal HSIL+ was 1.21 (95% CI: 0.73-2.03).This is the first study to demonstrate that HPV vaccination at a younger age is associated with substantially reduced risk of anal HSIL+ in the general population.