The inverse association between non-melanoma skin cancer and alopecia areata: A systematic review and meta-analysis

Non-melanoma skin cancers (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are the most common malignancies worldwide and remain clinically relevant in survivorship care. While many autoimmune diseases carry increased cancer risk, alopecia areata (AA), a T cell-mediated autoimmune disease, may instead confer enhanced cutaneous tumor immunosurveillance. We conducted a systematic review and meta-analysis to evaluate NMSC risk in AA and assess its potential as a human model of immune-mediated cancer protection. PubMed, Embase, Scopus, and ClinicalTrials.gov were searched through July 2025 for observational studies reporting BCC or SCC incidence in AA versus controls. Effect estimates were pooled using random-effects models with REML and Hartung-Knapp adjustment. Heterogeneity was assessed with I 2 and leave-one-out sensitivity analyses. Eight retrospective cohorts (n = 854,000 AA patients) met inclusion criteria, four reported BCC and five SCC outcomes. Across studies, AA patients consistently demonstrated lower skin cancer incidence compared with controls (OR 0.58; 95% CI, 0.27-1.22). Pooled estimates suggested reduced risk for BCC (OR 0.43; 95% CI, 0.11-1.75) and SCC (OR 0.66; 95% CI, 0.28-1.57), though neither reached statistical significance. Between-study heterogeneity was high (I 2 > 80%), reflecting differences in study design, case ascertainment, and adjustment for UV exposure, phototype, and treatment history. Sensitivity analyses confirmed stability of the protective direction, with no evidence of publication bias detected. These findings support a possible inverse association between AA and NMSC, contrasting with malignancy patterns seen in other autoimmune conditions. AA may represent a natural model of heightened cutaneous immune surveillance, with relevance to understanding cancer risk in the context of JAK inhibition and immune signaling. Further prospective studies with standardized outcome definitions, including diverse patient populations, are warranted to validate this association and explore translational implications for cancer prevention and survivorship care.