Real-World Effectiveness of Human Papillomavirus Vaccination Against Vulvovaginal High-Grade Precancerous Lesions and Cancers

BACKGROUND: Vaccination against human papillomavirus (HPV) has proven to be effective against severe cervical lesions and genital warts, whereas no previous study has provided real-world data on the HPV vaccine effectiveness against high-grade vulvovaginal lesions.

METHODS: A cohort of all women age 17-26 years living in Denmark during 2006-2019 was followed in nationwide registers for individual-level information about HPV vaccination and first diagnoses of vulvar and vaginal high-grade squamous intraepithelial lesions (HSIL+) or worse. The cumulative incidence of vulvar and vaginal HSIL+, respectively, was estimated with the Aalen-Johansen estimator, and Cox proportional hazards regression was used to estimate hazard ratios (HRs) for vulvar and vaginal lesions separately, comparing women vaccinated at age 16 years or younger and at age 17-26 years with unvaccinated women.

RESULTS: The cohort consisted of 514 537 women, of which 50.6% were vaccinated at baseline (<16 years), 31.8% were vaccinated during follow-up (17-26 years), and 17.6% remained unvaccinated. The cumulative incidence was less than 0.6‰ for vulvar HSIL+ and less than 0.2‰ for vaginal HSIL+. Adjusted analyses showed reduced HRs for both vulvar (HR = 0.22, 95% confidence interval = 0.13 to 0.38) and vaginal HSIL+ (HR = 0.16, 95% confidence interval = 0.04 to 0.55) for women vaccinated at age 16 years or younger compared with unvaccinated women. For women vaccinated at 17-26 years of age, the reductions in HRs were smaller for vaginal HSIL+ and close to 0 for vulvar HSIL+.

CONCLUSIONS: HPV vaccination before 17 years of age reduces the risk of vulvar and vaginal HSIL+ based on real-world data.