HPV 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 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.

RESULTS: 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).

CONCLUSION: 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.