Genotoxicity in oral mucosal cells associated with e-cigarette use: a systematic review and meta-analysis

OBJECTIVES: To evaluate the effects of electronic smoking devices (e-cigarettes) on the genotoxicity of oral mucosal cells compared with conventional cigarette smokers and nonsmokers, and to critically assess the methodological frameworks generating this evidence. STUDY DESIGN: Searches were conducted up to July 2025 in PubMed, EMBASE, Scopus, Web of Science, CINAHL, Cochrane Library, LILACS, and grey literature. Eligible studies were observational designs assessing genotoxic damage in oral mucosal cells of adult e-cigarette users through the buccal micronucleus cytome assay (BMNcyt). Data extraction and risk of bias assessment (JBI checklists) were performed independently by two reviewers. Meta-analyses used random-effects models. RESULTS: Nine cross-sectional studies (n = 711) were included. Meta-analysis showed that e-cigarette users had significantly lower micronucleus (MN) frequency than smokers (mean difference: 2.75; 95% CI: 0.02-5.47; P = .048), but no significant difference compared with nonsmokers. Subgroup analysis indicated higher MN frequencies in e-cigarette users versus nonsmokers when ≥1,000 cells were analyzed per sample. Risk of bias ranged from low to high, and the certainty of the pooled evidence was rated as "very low." CONCLUSIONS: E-cigarettes induce less genotoxicity than conventional smoking but may increase DNA damage compared with nonsmokers under standardized BMNcyt protocols. Stronger prospective studies with methodological rigor are needed.