Abstract
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.
Highlights
IntroductionFirst described in the early1950s, is a potentially malignant disease predominantly seen in people of Asian descent
Oral submucous fibrosis, first described in the early1950s, is a potentially malignant disease predominantly seen in people of Asian descent
Thereby, it highlights the use of increased fibroblast Tissue inhibitors of matrix metalloproteinases (TIMPs)-1 and 2 levels as effective markers of early oral submucous fibrosis (OSF). Further studies regarding this finding have a clinical value as OSF may be reversed to normal at its early stage [9]. Another group has found that TIMP-1 production is enhanced when fibroblasts are co cultured with keratinocytes pretreated by arecoline
Summary
First described in the early1950s, is a potentially malignant disease predominantly seen in people of Asian descent. It is a chronic progressive disorder and its clinical features depend on the stage of the disease. The disease was described in 1950s, its pathogenesis and more importantly the mechanisms of malignant transformation have not been clear up to date. The aim of this review is to analyze critically the recent developments that may lead to our understanding of the pathogenesis (Figure 1) and malignant transformation of OSF (Figure 2). A special reference is made to emphasize the fact that arecanut contains definite carcinogens, promoting oral carcinogenesis
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