Oral submucous fibrosis: review on mechanisms of malignant transformation

Abstract

Research studies focusing on various aspects of carcinogenesis in the background of fibrosis have advanced significantly in the recent past, allowing us to understand the mechanisms involved in malignant transformation of oral submucous fibrosis (OSF), the most prevalent potentially malignant oral disorder in South Asia. The role of areca nut as a carcinogen has been proven beyond doubt, with a large number of animal studies demonstrating its carcinogenicity, mutagenicity, and genotoxicity. Studies on the molecules implicated in cell cycle regulation, hypoxia, processes leading to DNA double-strand breaks, senescence, and many other pathways related to carcinogenesis have shown ample evidence for the malignant transformation in OSF induced by areca nut. More importantly, the understanding of the mechanisms of malignant transformation may lead to early diagnosis of oral squamous cell carcinoma arising in the background of OSF, which is now considered to constitute a clinicopathologically distinct disease, and the differences are believed to arise from the differential mechanisms of areca nut carcinogenesis. Therefore, the objective of this study is to review the literature on the various mechanisms leading to the malignant transformation of OSF.