Oral Submucous Fibrosis: Review on Mechanisms of Pathogenesis and Malignant Transformation
Rasika Priyadharshani Ekanayaka and Wanninayake Mudiyanselage Tilakaratne*
Department of Oral Pathology, Faculty of Dental Sciences, University of Peradeniya, Sri Lanka
- *Corresponding Author:
- WM Tilakaratne
Faculty of Dental Sciences
University of Peradeniya, Sri Lanka
E-mail: [email protected]
Received Date: June 20, 2013; Accepted Date: July 29, 2013; Published Date: August 05, 2013
Citation: Ekanayaka RP, Tilakaratne WM (2013) Oral Submucous Fibrosis: Review on Mechanisms of Pathogenesis and Malignant Transformation. J Carcinogene Mutagene S5:002. doi: 10.4172/2157-2518.S5-002
Copyright: © 2013 Ekanayaka RP, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Studies focusing on epidemiology, histopathology and molecular biology/pathology on various aspects of oral submucous fibrosis (OSF), especially in the last decade have helped to understand the pathogenesis to a larger extent. In addition research in some aspects of carcinogenesis in the background of fibrosis has also advanced significantly in the recent past allowing us to understand the mechanisms involved in malignant transformation of the most prevalent oral potentially malignant disorder in South Asia. It has been shown that pathogenesis of OSF is directly related to arecoline present in arecanut and most of the alterations in various pathways and molecules leading to accumulation of collagen are mediated as a result of arecoline. Reduction of Matrix metalloproteinases (MMPs) and increased secretion of Tissue inhibitors of matrix metalloproteinases (TIMPs) play the most significant role in collagen accumulation whilst fibrogenic cytokines, mainly TGF-β over expression leads to increased production of collagen. There are various other pathways/molecules contributing to the pathogenesis in varying capacities. Malignant transformation in OSF has also been studied by various groups in the recent past. Role of arecanut as a carcinogen is proven beyond doubt with a large number of animal studies demonstrating its carcinogenicity, mutagenicity and genotoxicity. Studies involved in many 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 arecanut induced malignant transformation in OSF. Some of the findings in these studies may be helpful in inventing new treatment strategies for a common disease without an effective treatment up to date. Further, the understanding of mechanisms of malignant transformation may lead to early diagnosis of oral squamous cell carcinoma (OSCC) arising in the background of OSF.