Mitotic and apoptotic indices in oral epithelial dysplasia and oral squamous cell carcinoma: A systematic review
Swati S. Gotmare, Treville Pereira, Pooja Kamath, Subraj Shetty, Sanpreet S. SachdevAbstract
Background:
Oral carcinogenesis is associated with an altered balance between cellular proliferation and apoptosis. Mitotic index (MI) and apoptotic index (AI) were evaluated as tissue-based indicators of progression across oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC); however, the available evidence is methodologically heterogeneous. This review evaluated the patterns of MI and AI and examined the supportive contribution of related biomarkers.
Methodology:
PubMed, Scopus, Embase, ScienceDirect, and Google Scholar databases were searched since inception to March 2025. Studies assessing direct MI or AI, or surrogate proliferation and apoptosis biomarkers, in histopathologically confirmed OED and OSCC were included. Two reviewers independently performed study selection and data extraction. Risk of bias was assessed using design-appropriate Joanna Briggs Institute (JBI) checklists, and certainty was evaluated using GRADE. Owing to methodological and outcome heterogeneity, a narrative synthesis was performed.
Results:
Of 1,719 identified records, 784 were screened and 19 studies were finally included. Seven studies evaluated direct MI and 11 evaluated direct AI, while other studies assessed Ki-67, PCNA, AgNOR, Bax, Bcl-2, or methylation-derived markers. Direct morphological evidence generally demonstrated increasing MI with progression from normal mucosa through OED to OSCC. AI showed a less consistent pattern across lesion grades and tumor differentiation. Proliferation and apoptosis biomarkers provided supportive biological evidence but were not considered equivalent to conventional indices. The certainty of evidence ranged from low to very low.
Conclusion:
MI may provide a useful adjunctive indication of increasing proliferative activity across oral epithelial lesions, whereas AI appears to reflect more variable biological changes. Standardised prospective studies are required before these indices or their surrogate biomarkers can be recommended for routine diagnostic or prognostic use.