Micronuclei in the Buccal Mucosal Cells are Genotoxicity Markers in Oral Potentially Malignant Disorders: A Systematic Review and Meta-Analysis

Objective: Micronuclei (MN) genotoxicity, linked to chromosomal anomalies, is a key biomarker for carcinogen exposure and cancer susceptibility, with higher frequencies observed in cancer patients. The micronuclei assay, using exfoliated buccal cells, offers a non-invasive method for diagnosing oral lesions caused by tobacco, betel nut, and alcohol. This review aims to systematically review micronuclei frequencies in buccal mucosal cells and assess their potential as genotoxicity markers in oral potentially malignant disorders (OPMD). Methods: A systematic search updated to 2024 was conducted using PubMed, Scopus, ProQuest, Cochrane, and Google Scholar for original studies analyzing micronuclei frequencies in buccal cells as genotoxicity markers for OPMD. Studies including leukoplakia, lichen planus, and OSMF, were selected. The assessment of risk bias was done using modified Newcastle-Ottawa Scale followed by meta- analysis. The review was registered in PROSPERO (Registration No. CRD42024536661).  Results: Twenty-six articles encompassing a pooled sample of 1,078 healthy controls and 1,489 OPMD cases (417 leukoplakia, 180 oral lichen planus, 401 OSMF, and 491 unsegregated OPMDs) were included. A significant increase in micronuclei frequency was observed in OPMD patients compared to controls (meta-Cohen’s d = 3.08, 95% CI: 1.80-4.35). Subgroup analysis revealed a gradual rise in MN frequency from healthy controls to leukoplakia (d = 2.75), oral lichen planus (d = 1.47), and the highest in oral submucous fibrosis (d = 5.55). Considerable heterogeneity was detected among studies (overall I² = 99.23%, OSMF I² = 99.85%, lichen planus I² = 49.59%). This variability highlights methodological and population differences across studies. Conclusion: Micronuclei genotoxicity is emerging as a valuable biomarker for the early detection of OPMD’s. Due to its non-invasive and cost-efficient characteristics, examining micronuclei in exfoliated buccal cells could be incorporated into regular screenings for groups at high risk of OPMD and oral cancer. However, the considerable variability among studies necessitates careful interpretation and highlights the importance of establishing standardized protocols in future research.