Background: Oral squamous cell carcinoma (OSCC) is usually preceded by clinically visible changes on oral mucosa categorized as oral potentially malignant disorders (OPMD). The progression of OPMD to OSCC is a multistep process that provides an opportunity for early cancer detection and interception. Recent research suggests that cancer stem cells (CSC) hold the key to unlocking effective strategies to curb initiation and growth of several malignant neoplasms, including OSCC. In this meta-analysis, we evaluated the efficacy of CSC markers CD133, podoplanin, ALDH1, and others in predicting risk of malignant transformation of OPMDs. Methods: The PubMed database was systematically reviewed for relevant articles. Quality of eligible studies was assessed as per reporting recommendations for tumor marker (REMARK) criteria. A total of 18 investigations from 12 studies evaluated clinical or prognostic significance of CSC markers in OPMDs. A reasonable number of patients (1,659) were included in this analysis. Results: Positive expression of CSC markers in OPMDs is significantly associated with progression to OSCC [risk ratio (RR), 3.31; 95% confidence interval (CI), 2.72-4.02]. Variability in CSC population makes it difficult to understand exact biology of OPMDs based on single CSC marker investigation. Conclusions: Identifying CSC population is a reliable prognostic indicator in OPMDs with or without dysplasia. Multi-marker panel investigation for CSCs in OPMDs may assist in curtailing new cases of oral cancer to a great extent. Impact: The study illustrates that evaluating CSC marker expression in OPMDs is a key tool in identifying high-risk cases to prevent development of OSCC.

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