Dermatology · Medical Literature
Intralesional human papillomavirus vaccination for cutaneous verrucae: a systematic review and meta-analysis of therapeutic efficacy.
Abstract
To evaluate the efficacy of intralesional human papillomavirus (HPV) vaccination in the management of cutaneous warts. 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. 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. 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.
Clinical relevance
In patients with chronic or treatment-refractory cutaneous warts, does intralesional HPV vaccination achieve significantly higher rates of complete wart clearance compared with intralesional normal saline? __SNAPSHOT__ {"studyDesign":"Systematic review and meta-analysis (PROSPERO-registered: CRD420251170324); random-effects model","setting":"Multi-database search (PubMed, MEDLINE, Embase, Scopus, ClinicalTrials.gov) through March 2026; all six included studies were conducted in Egypt","sampleSize":"6 studies included; total patient count not reported in abstract; n=124 patients reported to have experienced an adverse event","population":"Patients with chronic or persistent cutaneous warts (lesions lasting >6 months or with inadequate response to conventional therapies); at least 1 dose of intralesional HPV vaccine required; comparator group required for inclusion","intervention":"Intralesional HPV vaccination (bivalent or quadrivalent formulations)","comparator":"Intralesional normal saline (placebo comparator)","primaryOutcome":"Complete wart clearance (pooled risk ratio with 95% CI)","followUp":"Not reported","fundingSource":"Not reported"}
Key findings
In the primary pooled analysis (6 studies, random-effects model), intralesional HPV vaccination was associated with a significantly higher rate of complete wart clearance compared with intralesional normal saline (RR 18.54; 95% CI 6.59–52.18). Heterogeneity was notably low (I² = 0%; p = .97 for the heterogeneity test), suggesting consistent direction of effect across included studies. In subgroup analyses by vaccine valency, bivalent HPV vaccine demonstrated an RR of 14.05 (95% CI 3.57–55.32; I² = 0%; p = .83), and quadrivalent HPV vaccine demonstrated an RR of 26.78 (95% CI 5.52–129.82; I² = 0%; p = .95); the wide and overlapping confidence intervals preclude a definitive conclusion of superiority of one formulation over the other. NNT cannot be calculated from the abstract, as absolute event rates in intervention and control groups were not reported. Adverse events were mild and localized; all 124 participants who experienced an adverse event reported only tolerable injection-site pain. No serious adverse events were described.
Practice implications
This meta-analysis demonstrates a statistically robust association between intralesional HPV vaccination and complete clearance of chronic or treatment-refractory cutaneous warts versus placebo injection, with no significant heterogeneity across studies. However, several critical limitations restrict the immediate translatability of these findings. All six included studies originated from Egypt and appear to involve overlapping investigator groups from a limited number of institutions, raising serious concerns about geographic and institutional selection bias and limiting generalizability to diverse patient populations. Absolute clearance rates for both intervention and control arms were not reported in the abstract, making it impossible to estimate NNT or confirm clinical magnitude of benefit beyond the relative measure. The extremely wide confidence intervals for subgroup analyses (e.g., quadrivalent RR upper bound 129.82) reflect small underlying study numbers and should be interpreted with caution. The comparator was normal saline rather than standard-of-care therapies (e.g., cryotherapy, salicylic acid), so the study does not establish superiority over established treatments. Dosing regimens, number of sessions, wart types, patient age, immunocompetence status, and duration of follow-up were not described in the available abstract. The finding is consistent with earlier narrative reviews and individual RCTs suggesting intralesional HPV vaccination may benefit recalcitrant wart patients, but independent replication in geographically diverse, adequately powered RCTs using active comparators is needed before routine clinical adoption. Only the abstract was available for this summary, which limits full methodological appraisal. __LIMITATIONS__ All six included studies conducted in Egypt with overlapping investigator groups, severely limiting geographic generalizability and raising concern for systematic bias,Small number of included studies (n=6), with wide confidence intervals in subgroup analyses indicating imprecision,Comparator was normal saline, not active standard-of-care; superiority over established wart therapies (cryotherapy, salicylic acid, etc.) is not established,Absolute clearance rates not reported in abstract; NNT cannot be calculated,Follow-up duration not reported; recurrence rates after clearance not described,Dosing protocols, number of treatment sessions, wart subtypes, and patient immunocompetence status not specified in abstract,Potential inclusion of overlapping patient populations across studies given institutional concentration,No assessment of blinding adequacy or risk of bias in individual included studies available from abstract alone,Funding source not reported; potential conflicts of interest cannot be assessed,Only abstract available; full methodological appraisal not possible __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ This systematic review and meta-analysis of 6 studies reports a large relative benefit of intralesional HPV vaccination over saline placebo for complete clearance of chronic cutaneous warts (RR 18.54; 95% CI 6.59–52.18), with low heterogeneity and a favorable tolerability profile. However, all included studies originate from Egyptian institutions with overlapping investigator groups, the comparator was placebo rather than active standard-of-care therapy, and absolute effect sizes are not reported, making NNT estimation impossible. Intralesional HPV vaccination is a promising immunotherapeutic option for treatment-refractory warts but requires independent replication in geographically diverse, adequately powered trials with active comparators before it can be considered for routine practice change.