Oral submucous fibrosis: A global challenge. Rising incidence, risk factors, management, and research priorities.

Oral submucous fibrosis is a potentially malignant disorder of the oral cavity, with a high rate of malignant transformation. It is very common among habitual areca nut chewers. The pathogenesis of oral submucous fibrosis is not well established, but it is believed to be a disease of multifactorial origin, including areca nut chewing, ingestion of chilies, genetic factors, immunologic processes and nutritional deficiencies. Genetically susceptible individuals when exposed to areca nut chewing develop this disease over a variable period of time. Oral submucous fibrosis is considered to be a disease of collagen metabolism. Several genetic factors are reported but there is no consensus about the exact mechanism of disease initiation. Variations in histopathological presentation are noted among oral submucous fibrosis patients with habitual areca nut chewing in different forms and other additive agents, eg betel quid, pan masala and gutkha, together with a variety of tobacco habits. The role of epigenetic modifications, such as miRNA regulation, and DNA methylation is also being reported as part of the pathogenesis of oral submucous fibrosis. A combined approach, including analysis of genetic and epigenetic regulations with different habits, might be helpful to better understand the contributory factors and pathogenesis of this serious disorder.