Abstract
BACKGROUND: Each year, 45,000 women worldwide develop vulvar cancer, often occurred from vulvar high-grade squamous intraepithelial lesions (vHSIL), a precancerous stage associated with high- risk human papillomavirus (HPV). Recurrent vHSIL, experienced by over 30% of patients despite treatment, conducting in significant physical and psychosocial challenges. With no established method to reduce recurrence, our study investigates the potential of adjuvant HPV vaccination during treatment. We aim to determine whether nonavalent HPV vaccination can effectively prevent vHSIL recurrence in women treated for vulvar HSIL. METHODS: This is a randomized, double-blind, placebo-controlled study protocol involving 498 women diagnosed with vHSIL. Participants will be randomized to receive either the nonavalent HPV vaccine or a placebo in addition to standard treatment. The primary outcome is the recurrence of vHSIL within 24 months following treatment. Secondary endpoints are treatment effectiveness, immune response, cost-effectiveness, and quality of life. Long-term follow-up examines vaccine effect after 5 and 10 years, along with the occurrence of vulvar malignancies. Relative risk between vaccinated and placebo groups will be evaluated, employing intention-to-treat principles. DISCUSSION: This study is designed to investigate the potential benefits of HPV vaccination in managing vHSIL. Results from the trial will provide evidence on the vaccine's impact on recurrence rates, treatment outcomes, and long-term prevention of vulvar malignancies. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT06052696. Registered 12 January 2023, https://clinicaltrials.gov/study/NCT06052696 .