Therapeutic potential of intramuscular HPV vaccine on recalcitrant warts: A systematic review and IPD meta-analysis

Abstract

Background: Recalcitrant warts, often unresponsive to standard treatments, lead to a significant clinical challenge. Emerging evidence suggests intramuscular HPV vaccination may offer therapeutic benefit. Objective: To evaluate the efficacy of HPV vaccination for wart resolution and identify response predictors through an individual patient data meta-analysis. Methods: This systematic review and individual patient data meta-analysis followed PRISMA-IPD guidelines and was registered in PROSPERO (CRD420251051106). Six databases were searched for studies published before March 2025 involving patients with recalcitrant warts treated with intramuscular HPV vaccines. Inclusion required reported treatment outcomes. Two reviewers independently screened, extracted, and assessed risk of bias. Outcomes were analyzed using Kaplan–Meier survival analysis with subgroup comparisons by age, wart location, immune status, and vaccine type based on cases with known time to clearance. Results: A total of 183 patients with recalcitrant warts from 27 studies (mean age 31.7 years) were included. The most common site was anogenital. Complete resolution occurred in 61.2% of cases (112/183). Among immunocompromised patients, a clinical response (complete or partial clearance) was achieved in 92.9% (13/14). Responders were significantly younger, with no outcome differences by vaccine type, concurrent treatment, sex, or comorbidities. Time-to-event analysis based on 168 patients with known time to complete clearance showed a median time to cure of 24 weeks with a 6-month cumulative cure rate of 52.4%. Reported adverse events were mild and transient. Conclusions: Intramuscular HPV vaccination has shown encouraging outcomes. Although current evidence is based on uncontrolled studies, further controlled studies are warranted to confirm these findings.