Exploring Cancer‐Associated Fibroblasts in OSCC and OPMDs: Microenvironment Insights. Scoping Review

Introduction: The tumor microenvironment (TME) plays a crucial role in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). Despite progress, the mechanisms behind the TME-epithelial cell interaction remain unclear. Cancer-associated fibroblasts (CAFs), the most abundant cells in the TME, require further study. Material and methods: We conducted a scoping review, searching for clinical and vivo studies that discuss the role of CAFs in OSCC and OPMDs progression. Results: From 1152 PubMed results, 29 studies met the inclusion criteria. CAFs, identified as αSMA+ cells, interact with the TME and epithelial cells by secreting various molecules. In OSCC, CAF signals contribute to a pro-tumorigenic environment, and CAF numbers positively correlate with tumor grade, size, stage, aggressiveness, and mortality. While limited data exist on CAFs in OPMDs, they seem linked to malignant transformation risk. Discussion: CAFs are critical in OSCC pathophysiology, but the complex intercellular mechanisms are not fully understood. Currently, CAFs are not part of clinical decision-making, but emerging evidence suggests they could represent a promising new approach in managing OSCC and OPMDs. Conclusion: Future research should aim to gain a deeper understanding of how CAFs contribute to OSCC progression and their role in OPMDs pathophysiology.