Vitiligo and Skin Cancer Risk: A Systematic Review and Meta‐Analysis With Subtype and Phototherapy Stratification

Background

Vitiligo is an autoimmune disorder characterized by CD8+ T cell‐mediated melanocyte destruction and a pro‐inflammatory immune milieu. Despite frequent use of ultraviolet‐based phototherapy, emerging evidence suggests that vitiligo may paradoxically confer a reduced risk of skin cancer. Clarifying this association may provide insight into tumor immune surveillance and inform risk assessment in patients with vitiligo.

Objectives

To evaluate the association between vitiligo and the risk of melanoma and non‐melanoma skin cancers (NMSC), and to assess the potential impact of phototherapy exposure on skin cancer risk.

Methods

A PRISMA‐compliant systematic review and meta‐analysis searched PubMed, Scopus, Embase, and ClinicalTrials.gov through January 2026 for studies comparing skin cancer incidence in patients with vitiligo versus controls. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using Hartung‐Knapp random‐effects models, with assessment of heterogeneity and publication bias.

Results

Fourteen studies were included (454,307 vitiligo patients; 3,583,147 controls), of which nine were eligible for meta‐analysis. Vitiligo was associated with lower odds of melanoma (OR 0.43; 95% CI, 0.16–1.13), with consistent inverse associations across sensitivity analyses. A similar inverse trend was observed for NMSC overall (OR 0.29; 95% CI, 0.06–1.49). Squamous cell carcinoma risk was significantly reduced (OR 0.76; 95% CI 0.57–0.99; p  = 0.045), while basal cell carcinoma showed a non‐significant inverse association (OR 0.54; 95% CI, 0.26–1.11). Phototherapy exposure was associated with higher point estimates for melanoma (OR 1.87; 95% CI 0.53–6.54) and NMSC (OR 1.46; 95% CI, 0.37–5.69), although neither association reached statistical significance. Funnel plots and Egger's testing did not detect publication bias.

Conclusions

Vitiligo was associated with lower odds of melanoma and NMSC, with a statistically significant reduction for squamous cell carcinoma. Phototherapy exposure showed higher but non‐significant point estimates. These findings provide a benchmark for baseline cancer risk in vitiligo and may inform safety monitoring of phototherapy and emerging immunomodulatory therapies.

PROSPERO number: CRD42024619708.