Intralesional human papillomavirus vaccination for cutaneous verrucae: a systematic review and meta-analysis of therapeutic efficacy

Clinical Snapshot

Key Findings

• P Value: Not explicitly reported in abstract; confidence interval does not cross 1.0, indicating statistical significance at p < 0.05

• Effect Size: Pooled Risk Ratio (RR) 18.54 — intralesional HPV vaccination associated with an 18.54-fold higher rate of complete clearance compared with saline control

• Primary Outcome: Complete wart clearance with intralesional HPV vaccination versus intralesional normal saline

• Nnt Or Sensitivity: NNT not calculable from abstract data alone (absolute event rates in intervention and control arms not provided). Subgroup analysis: bivalent and quadrivalent HPV vaccines demonstrated comparable efficacy (specific RRs per subgroup not reported in abstract)

• Confidence Interval: 95% CI: 6.59 to 52.18

Clinical Application

Intralesional injection of HPV vaccine is a procedural intervention requiring trained clinical staff, appropriate injection technique, and access to HPV vaccine stock. The procedure is feasible in dermatology outpatient settings. Adverse events reported as mild and localised suggest an acceptable safety profile for clinical use. However, the off-label nature of this application, the number of injections required per treatment course, and optimal dosing intervals are not defined by this review. In Australia, HPV vaccines (Gardasil 9 — nonavalent; previously Gardasil — quadrivalent and Cervarix — bivalent) are TGA-registered for prophylactic use against HPV-related disease. Intralesional use for cutaneous warts is off-label and not currently listed on the PBS for this indication. The RACGP does not currently include intralesional HPV vaccination in guidelines for wart management. Conventional treatments (salicylic acid, cryotherapy) remain first-line per Australian dermatology practice. Gardasil 9 is available through the National Immunisation Program (NIP) for adolescents, but adult access for off-label intralesional use would require private prescription and out-of-pocket cost. TGA approval for this indication would require further high-quality RCT evidence. Clinicians considering this approach should obtain informed consent regarding off-label use and document treatment-refractory status. Adults and potentially adolescents with chronic, persistent, or treatment-refractory cutaneous warts (verrucae vulgaris and related subtypes) who have failed conventional first-line therapies such as salicylic acid, cryotherapy, or electrosurgery. The intervention may be particularly relevant for immunocompetent patients with multiple or recalcitrant lesions.

Abstract

OBJECTIVES: To evaluate the efficacy of intralesional human papillomavirus (HPV) vaccination in the management of cutaneous warts. METHODS: A comprehensive search of PubMed, MEDLINE, Embase, Scopus, and ClinicalTrials.gov was conducted in accordance with a registered PROSPERO protocol (CRD420251170324). Chronic or persistent warts were defined as lesions lasting more than six months or showing inadequate response to conventional therapies. The primary outcome was complete wart clearance, and pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Six studies were included. Intralesional HPV vaccination was associated with a significantly higher rate of complete clearance compared with intralesional normal saline (RR 18.54; 95% CI 6.59-52.18). Subgroup analyses demonstrated comparable efficacy between bivalent and quadrivalent vaccines. Reported adverse events were mild and localized. CONCLUSION: Intralesional HPV vaccination demonstrated significant therapeutic efficacy in the treatment of cutaneous warts and represents a promising immunotherapeutic option for patients with persistent or treatment-refractory disease.

References

1. 1.Leeyaphan, C., Bunyaratavej, S., Jirawattanadon, P., Bhorntarakcharoen, W., Chaichanamongkol, P., & Kanchanasurakit, S. (2026). Intralesional human papillomavirus vaccination for cutaneous verrucae: a systematic review and meta-analysis of therapeutic efficacy. Journal of Dermatological Treatment. Advance online publication. https://doi.org/10.1080/09546634.2026.2688574