Meta-Analysis and Systematic Review of Immune Checkpoint Expression in Predicting the Risk of Malignant Transformation in Oral Potentially Malignant Disorders

INTRODUCTION AND AIMS: Immune checkpoints (ICPs) play a critical role in tumour immune evasion, yet their significance in oral potentially malignant disorders (OPMDs) remains poorly defined. This study evaluates the evidence regarding ICPs in predicting malignant transformation (MT) of OPMDs and identifies research gaps. METHODS: A systematic synthesis was conducted of studies investigating ICP expression in predicting the MT risk of OPMDs. A search strategy was developed and applied across the PubMed, Scopus, and Web of Science Core Collection databases to identify articles relevant to this topic. RESULTS: Of the 231 publications retrieved, 5 met the inclusion criteria, encompassing a total of 613 patients, among whom 129 experienced MT, corresponding to an MT rate of 21.04%. A total of 2 ICPs were evaluated. Among these, PD-L1 was identified in several studies as having potential utility in predicting the MT risk of OPMDs. However, its clinical application requires further investigation, and clinical evidence regarding the role of other ICPs in predicting MT risk remains lacking. CONCLUSION: The role of ICPs in predicting the MT risk of OPMD remains underexplored with fragmented evidence. While the PD-1/PD-L1 axis shows promise, its clinical utility remains unestablished. Prospective studies and randomized trials are further needed. CLINICAL RELEVANCE: Elucidating ICP roles in OPMDs could enable precise risk stratification and immunopreventive strategies, facilitating early intervention and reducing oral cancer incidence.