α-Smooth muscle actin (Myofibroblast) as a marker of disease progression and malignant transformation in oral submucous fibrosis: A systematic review and meta-analysis.

OBJECTIVE

This systematic review and meta-analysis sought to evaluate whether stromal myofibroblast assessed by alpha-smooth muscle actin (α-SMA) expression serves as a reliable biomarker of disease progression and malignant transformation (MT) potential in oral submucous fibrosis (OSMF).

DESIGN

A systematic review and meta-analysis was carried out using the PRISMA protocol, which was registered in the PROSPERO database. The databases searched included PubMed, Scopus, and Web of Science, and the search period was up to January 2026. The included studies had data regarding the assessment of α-SMA expression in normal oral mucosa (NOM), OSMF, and oral squamous cell carcinoma (OSCC). The methodological quality of each study was assessed using the Newcastle-Ottawa Scale. Random effects models using standardized mean difference (SMD) and odds ratio (OR) were used.

RESULTS

Seventeen studies included meeting the inclusion criteria. Narrative synthesis revealed a stepwise increase in stromal α-SMA expression from NOM to early OSMF, advanced OSMF, and OSCC with transition in architecture from focal to diffuse and networked pattern of stroma. Quantitative meta-analysis results demonstrated significantly higher α-SMA expression in OSMF compared to NOM (SMD = 1.82), in advanced compared with early OSMF (SMD = 1.17), and in OSCC compared with OSMF (SMD = 1.51). Dichotomous analysis revealed an overall significantly increased odds of high α-SMA expression in OSMF (OR = 7.28) and OSCC (OR = 11.19). Fifteen studies had a low risk of bias.

CONCLUSION

The increase in the expression of α-SMA demonstrates a strong graded association with OSMF severity and MT, supporting its value as a reproducible histopathologic biomarker for disease stratification and prognostic assessment.