HPV Vaccination as Treatment for Cutaneous Diseases: Beyond Prevention

Abstract Human papillomavirus (HPV) causes cutaneous diseases ranging from common warts to cutaneous squamous cell carcinoma (cSCC). Although HPV vaccines were licensed to prevent anogenital infections, they are increasingly used off-label to treat established HPV-associated cutaneous lesions. This narrative review evaluates therapeutic HPV vaccination for recalcitrant warts, non-melanoma skin cancer (NMSC), and immunocompromised populations. The only large randomized controlled trial showed no benefit for anogenital warts, and all positive evidence derives from low-quality studies with small sample sizes and heterogeneous designs. Publication bias is likely. Key challenges include lack of coverage for oncogenic β-HPV subtypes and the off-label nature of therapy. Future directions require next-generation vaccines targeting cutaneous HPV types and well-designed trials. Pending robust data, therapeutic HPV vaccination should remain strictly investigational and should be offered only within the context of clinical research or after explicit shared decision-making, rather than as a routine clinical option.