Abstract
The impact of HPV vaccination on cervical cancer and condylomas is well-established, but its effectiveness against high grade vulvar and vaginal lesions (VIN/VaIN) and related cancers remains less clear due to their rarity. This systematic review assessed the efficacy of quadrivalent (qHPV) and 9-valent (9vHPV) vaccines in both primary and tertiary prevention of these conditions. Eleven studies met the inclusion criteria. qHPV showed 100% efficacy against HPV16/18-related VIN/VaIN and cancers in per-protocol populations, with reduced but still significant efficacy (71%) in intention-to- treat analyses. The 9vHPV vaccine further reduced risks associated with additional HPV types (31/33/45/52/58). Real-life data revealed decreased incidence of vulvar and vaginal cancers following vaccination, particularly among younger women. While vaccination appeared to reduce recurrence rates after initial treatment of HPV-related lesions, randomized trials have not confirmed a clear adjuvant benefit. Overall, HPV vaccination proves highly effective in preventing vulvar and vaginal disease, especially when administered before HPV exposure.PROSPERO number: CRD420250638054.