Exploring the role of angiogenesis in fibrosis and malignant transformation in oral submucous fibrosis: a systematic review and meta-analysis

Angiogenesis is a crucial molecular driver of fibrosis in various inflammatory lesions. Oral submucous fibrosis (OSMF) is a chronic inflammatory fibrotic disorder with malignant potential. The angiogenetic pathways in OSMF remain obscure due to limited research, necessitating an in-depth review. This review aimed to illuminate the cryptic pathogenetic mechanisms of angiogenesis in the disease progression/fibrosis of OSMF and its malignant transformation, providing insights for improved treatment. Extensive literature searches were conducted across an array of databases until October 2023. Original research articles on angiogenesis in OSMF were included, and the risk of bias was assessed using the modified Newcastle-Ottawa scale. RevMan ver. 5.4 (Cochrane Collaboration) was used for data analysis. Thirty-four articles were included for qualitative synthesis and seven for quantitative analysis. Findings revealed that angiogenesis was significantly increased in early-stage OSMF but decreased as the disease advanced. It was also associated with the severity of epithelial dysplasia and malignant transformation. A random-effects model confirmed the upregulation of angiogenesis as a significant risk factor in early-stage fibrosis and malignant transformation. The mounting evidence reinforces that angiogenesis plays a crucial role in the progression of early-stage fibrosis of OSMF and its malignant transformation, opening avenues for diagnostic and therapeutic interventions.