Human papillomavirus vaccination and anal high-grade precancerous lesions and cancer-a real-world effectiveness study

Background: 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. Methods: We investigated HPV vaccine effectiveness against anal high-grade squamous intraepithelial lesion (HSIL) or worse in a nationwide cohort including all Danish women aged 17-32years during October 2006 to December 2021 (n = 968 881). HPV vaccinations and first occurrence of anal HSIL or worse 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 or worse according to vaccination status. Results: During follow-up, the number of incident histological anal HSIL or worse cases was 37 in unvaccinated women, and less than 5 and 26 in women vaccinated at ages younger than 17years and 17-32years, respectively. The overall number of cancers was less than 5. Compared with unvaccinated women, the risk of histological anal HSIL or worse was reduced for women vaccinated at age younger than 17years (HR = 0.30, 95% CI = 0.10 to 0.87). For women vaccinated at age 17-32years, the hazard rate of anal HSIL or worse was 1.21 (95% CI = 0.73 to 2.03). Conclusion: This is the first study to demonstrate that HPV vaccination at a younger age is associated with substantially reduced risk of anal HSIL or worse in the general population.