Mitochondrial DNA mutations in oral squamous cell carcinoma: A systematic review and meta-analysis

Abstract

Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral malignancies globally and remains a major health burden in South and Southeast Asia. Emerging evidence implicates mitochondrial dysfunction and mitochondrial DNA (mtDNA) mutations in OSCC carcinogenesis, progression, and prognosis. This systematic review and meta-analysis aimed to determine the pooled prevalence of mtDNA mutations in OSCC, map recurrent mutational hotspots, and evaluate their diagnostic and prognostic relevance. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, PubMed, Scopus, Web of Science, and EMBASE were searched (2000–2025) for observational studies analysing somatic mtDNA mutations in OSCC. Risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist for prevalence studies, and a DerSimonian–Laird random-effects proportional meta-analysis was performed. Subgroup analyses explored coding versus noncoding mutations, D-loop hotspots, and heteroplasmic versus homoplasmic patterns. Eight studies comprising 403 patients were included. The pooled prevalence of mtDNA mutations in OSCC was 88.1% (95% CI: 69.9–99.1). Individual study prevalence ranged from 26.7% (Yuan et al .) to 100% (Fendt, Kloss-Brandstätter, Mondal (b), and Palodhi). Heterogeneity was high (I² = 94.9%, Cochran’s Q = 137.97, P < 0.001; τ² = 0.3467). In the leave-one-out sensitivity analysis, the pooled prevalence ranged from 84.5% to 93.6%. These findings indicate that mtDNA mutations are highly prevalent in OSCC, although heterogeneity is considerable; larger standardised studies are needed to establish their diagnostic and prognostic value.