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An Official Publication of the Indian Association of Oral and Maxillofacial Pathologists

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Year : 2017  |  Volume : 21  |  Issue : 3  |  Page : 330-331

Oral submucous fibrosis: An update

1 Department of Oral Pathology, Dr. R. Ahmed Dental College and Hospital, Kolkata, West Bengal, India
2 Department of Oral and Maxillofacial Pathology, V.S. Dental College and Hospital, Bengaluru, Karnataka, India

Date of Web Publication15-Dec-2017

Correspondence Address:
Jay Gopal Ray
Department of Oral Pathology, Dr. R. Ahmed Dental College and Hospital, Kolkata, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jomfp.JOMFP_230_17

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How to cite this article:
Ray JG, Smitha T. Oral submucous fibrosis: An update. J Oral Maxillofac Pathol 2017;21:330-1

How to cite this URL:
Ray JG, Smitha T. Oral submucous fibrosis: An update. J Oral Maxillofac Pathol [serial online] 2017 [cited 2020 Jul 13];21:330-1. Available from: http://www.jomfp.in/text.asp?2017/21/3/330/220902

Oral submucous fibrosis (OSF) still remains a disease frequently encountered in a very restricted geographic location where areca nut is cultivated and consumed, and products such as pan masala and gutkha are readily available for consumption.

A very strong correlation between OSF and gutkha/pan masala abuse has been observed for many years. Areca nut being the most important constituent of these products has been identified as an independent group I human carcinogen, and several attempts to curb and regulate the use of gutkha and pan masala have been made in India.

In response to a public interest litigation to ban the substance a high court's judgment directed the central government to explore the harmful potential of these products. The Central Committee on Food Standards duly conducted an investigation and concluded that it was a dangerous food product. The committee recommended an outright ban on these products, but we are yet to see any effect.

Recent reports from across our nation and different other nations where gutkha chewers are at large a sharp decline in the age of onset of this disease is noticed and at the same time prevalence of OSF has increased from 0.03% to 6.42% in India. Why children and adolescents are getting addicted to this habit still remains questionable, but it could be due to lack of education, poor socio-economic condition and peer pressure, economical and easy availability, boosts a sense of well-being and satisfies hunger after chewing. Repeated intake of several packs per day increases the chance of early onset of this disease among genetically susceptible individuals.

High amounts of collagen production (mostly aberrant collagen), lack of collagen degradation and subsequent accumulation of collagen due to genetic and epigenetic modifications, other biochemical and molecular mechanisms still remains the main cause of this disease. The cause of many human diseases is due to jeopardy in the well-balanced interplay among a number of genetic, environmental and lifestyle factors. In OSF, single nucleotide polymorphisms can account for an increased (or decreased) likelihood of developing the disease. Genetically, susceptible individuals when exposed to areca nut chewing over a variable period may develop the disease. Genetic testing may provide prognostic information that allows an individual to make decisions about preventive measures such as lifestyle changes and more targeted medical follow-up. Although several genetic factors are reported, there is no consensus about the exact mechanism of disease initiation.

In OSF, once the overlying epithelium becomes altered and as the disease advances, the blood vessels are obliterated thereby reducing the possibility of clearing the metabolites from the diseased tissue and with further exposure to carcinogens the epithelium becomes more prone to undergo uncontrolled proliferation and invasion resulting in squamous cell carcinoma (SCC).

If we critically think about the disease OSF, it basically involves the connective tissue with fibrosis which increases with progression of the disease; whereas malignancy arises in the epithelium (SCC) and the term malignant transformation of OSF is used.

Fibrosis and cancer are known to be inextricably linked; however, very little is known about the common and overlapping molecular pathways between the two. Fibrosis and cancer initiation and progression is linked to the potent and pleiotropic growth factor transforming growth factor-β (TGF-β) which can induce both collagen and LOX expression. The highly fibrotic microenvironment may generate a more conducive environment around dormant tumor cells that then drives the transition from dormancy to growth. Activated fibroblasts and fibroblast-mediated extracellular matrix (ECM) remodeling have a prominent role in defining the rate and extent of cancer progression.

Repeated exposure to gutkha/Pan masala increases the possibility of oxidative stress mainly contributed by reactive oxygen species (ROS), ROS account for its genomic instability, resistance to apoptosis, proliferation and angiogenesis triggering cancer cell invasion through invadopodia formation. ROS promote activation and proliferation of fibroblasts and myofibroblasts, mostly by activating TGF-β pathway. Sustained myofibroblast activation stimulates dysfunctional repair mechanisms, leading to accumulation of fibrotic ECM that is rich in collagens that coalesce into fibrous bundles resistant to degradation. The fibrotic ECM disrupts cell polarity and stimulates cell proliferation, creating an environment for cancer development. However, carcinoma cells carry transformative mutations (as well as epigenetic changes) presumed to be absent in the fibrotic tissue.

When betel quid alone (betel nut and betel leaf) is chewed the incidence of OSF/OSF associated malignancy is not high but incidentally chewing gutkha (processed areca nut with tobacco) increases the possibility of OSF/OSF associated malignancy. It may be so that these products release high amounts of substances which can bring about fibrosis through different molecular and inflammatory pathways and at the same time causes genomic instability in the overlying epithelium through a set of other well-defined pathways wherein the epithelium gains proliferative ability. Therefore, it will not be wrong to presume that the underlying fibrosis makes the microenvironment more conducive for the transformed epithelial cell to seed in the fertile soil.

The first step in treatment OSF is to stop the habit of chewing gutkha/pan masala completely, supplemented with antioxidants, Vitamin A, elemental zinc, pentoxyphylline, interferon-gamma, colchicine and intralesional corticosteroids. Antioxidants possibly take care of the oxidative damage to the local tissue whereas Vitamin A helps in maintaining epithelial cell integrity. Elemental zinc administration has shown remarkable improvement in the clinical signs like reduction in burning sensation within a short time. Surgical modalities have been tried with variable response. Lasers for splicing the bands are also tried but are yet to prove much success. Stem cell in the treatment of OSF and nanotechnology-based approaches for reversal of the fibrotic connective tissue may have some future perspective.

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