A review on angio-fibrotic pathways driving cancer potential in oral submucous fibrosis

Oral Submucous Fibrosis (OSF) is a chronic, progressive, potentially malignant disorder associated with areca-nut exposure, characterized by persistent inflammation, extracellular matrix accumulation, and fibrotic restriction of oral function. This review highlights how fibrosis-driven vascular compromise and sustained hypoxia generate a tumor-promoting microenvironment that underlies malignant transformation. Dysregulated fibroblast activation, abnormal matrix remodeling, impaired angiogenesis, and chronic inflammatory signaling collectively promote stromal stiffness, oxidative stress, epithelial instability, and EMT-like changes. These interconnected angio-fibrotic and hypoxic mechanisms facilitate progression from fibrosis to epithelial dysplasia and ultimately oral squamous cell carcinoma. Understanding this pathogenic network provides a framework for early risk stratification and supports development of targeted anti-fibrotic and anti-angiogenic therapeutic strategies in OSF.