Human Papillomavirus Vaccines as Immunotherapy for Recalcitrant Verruca Vulgaris: A Systematic Evidence Synthesis

Recalcitrant verruca vulgaris (VV) is common, morbid, and notoriously resistant to first-line destructive therapies. Immunotherapeutic strategies that leverage human papillomavirus (HPV) vaccines have emerged as a promising option for patients with widespread or treatment-refractory disease. We synthesized study designs, vaccine formulations, administration routes, clinical outcomes, safety, and recurrence across eight studies encompassing randomized and nonrandomized trials, cohorts, and case reports. In aggregate, vaccines were associated with high rates of complete clearance at the study level, low recurrence where reported, and favorable tolerability. Intralesional administration often produced faster or more complete responses than intramuscular regimens in head-to-head comparisons. Quadrivalent and nine-valent vaccines demonstrated frequent complete responses in case series and case reports, while a randomized trial signaled benefits of combination immunotherapy using bivalent vaccine with Candida antigen compared with Candida alone. Adverse events were uncommon in this dataset and generally mild when reported. The overall evidence supports HPV vaccination as an effective immunotherapeutic approach for selected patients with recalcitrant VV, with route and formulation tailored to lesion burden, anatomic site, and patient tolerance. Standardized outcome definitions, patient- level response reporting, and long-term follow up will clarify durability and inform optimal sequencing with other immunotherapies.