The prognostic role of caspases in oral squamous cell carcinoma: A systematic review

Background : Oral squamous cell carcinoma (OSCC) is a common malignancy of oral cavity characterized by evasion of apoptosis, wherein caspases play a crucial role in apoptosis. There are only limited studies which examined expression of caspase in OSCC, their prognostic significance remains unclear due to the heterogeneity of the results across the studies. Aims and Objectives : To systematically review the literature evaluating the expression of caspases in OSCC and their potential role as prognostic markers. Methodology : This systematic review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD42024618007). A comprehensive search was conducted across PubMed, Scopus, Embase, Cochrane, and Google Scholar using MeSH terms related to OSCC and caspases. Case control studies involving evaluation of caspase expressions (e.g., caspase-3, -7, -8, -9) were included. Data extraction and risk of bias assessment were independently performed by two reviewers using the using a domain-based approach. Due to methodological heterogeneity, a narrative synthesis was made. Results : Out of 279 retrieved records, ten studies were included. Caspase-3 and cleaved caspase-3 were the most evaluated markers. While some of the studies revealed high caspase-3 and cleaved caspase-3 expression linked with poor prognosis and metastasis, other studies conversely reported decreased expression of caspase 3 in OSCC tissues. Caspase-7 was uniquely linked to recurrence and reduced disease-free survival. Discrepancies were attributed to variations in tumour site, stage, detection techniques, and potential non-apoptotic functions of caspases. Conclusion : Caspase expression in OSCC remains as an enigma, as it sometimes associated with contradictory prognostic implications. Further standardized, multicentric studies are required to delineate their definitive prognostic value, non-apoptotic role and its potential as therapeutic targets.