Elucidating the pathogenesis of oral submucous fibrosis: A comprehensive review

Oral submucosal fibrosis (OSMF) is a progressive and potentially malignant disorder of the oral cavity. This review aims to explore the key mechanisms underlying OSMF pathogenesis and its malignant transformation to oral cancer, focusing on the role of associated cells, growth factors, and signaling pathways, by detailing the sequential events within each pathway and their interconnections.

A comprehensive literature search was conducted using databases such as PubMed, Scopus, Google Scholar, and SciFinder to identify affected cells, pathways, and cellular mechanisms associated with OSMF and oral cancer.

This review elaborates the signaling pathways responsible for the progression of OSMF through myofibroblast activation. It highlights the altered functionality of key cellular players, including epithelial, endothelial, immune cells, and fibroblasts. It also enhances the understanding of OSMF pathophysiology by revealing the specific growth factors (TGF-βs, PDGF, FGF, VEGF, CTGF) and signaling pathways such as PI3K/AKT, JAK/STAT, WNT/β-catenin, and NF-кB, that are involved in the initiation and progression of OSMF and its malignant transformation to oral cancer.

This review identifies potential therapeutic targets and biomarkers within signaling pathways, mainly TGF-β and PI3K/AKT, that regulate fibroblast activation, inflammation, reactive oxygen species generation, collagen synthesis, and degradation in OSMF, which further leads to oral cancer development. In order to develop new treatments that target particular biomarkers, a deeper understanding of these signaling cascades is necessary.