Oral Sub-Mucous Fibrosis: A Narrative Review of Long-Term Malignant Disorder

Data from different studies provide a surprising hallmark that chewing areca nuts are the main symptom of oral submucous fibrosis. It is a long-term malignant disorder that narrows the mouth. Geographically, the prevalence of OSF is found in the Asia region at higher rates whereas the severity has not been seen in Pakistan. Common risk factors are deficiencies or iron, vitamins, and protein, immunological factors play a major role in the development of the disease. The possible mechanisms are found which is increased collagen synthesis and degradation. Recently, molecular biomarkers are fruitful in the treatment of OSF but further research is required. 

INTRODUCTION  

Oral mucosa, a membrane lining the inside of the mouth is exposed to stresses such as microorganisms and chemicals. These stresses expose acute and chronic reactive changes in the epithelium and connective tissues of the oral mucosa. Oral submucous fibrosis (OSF), first defined by Schwartz in 1952, is a precancerous form[1], insidious chronic progressive, and potentially malignant disorder of the oral cavity[2], caused by narrowing of mouth opening and pain during taking food. OSF is also known as idiopathic scleroderma of mouth, sclerosing stomality, and juxta epithelial fibrosis.

It is highly prevalent in South and Southeast Asia as well as globally accepted as Indian disease due to significant areca nut chewing habits [3]. Gutka, pan masala, tobacco, and smoking are reasons to be having oral submucous fibrosis disease. Recently, it has been recognized in Europe and North America. Symptoms include mouth dryness, weakened mouth movements, pain, and long term inability opening the mouth, hearing loss, and increased amount of saliva.

CLASSIFICATION CATEGORY

Many scientists have categorized oral submucous fibrosis into different types, stages, grades, and groups however widely accepted is Haider et al.[4] study which explains clinical staging and functional staging. The purpose was to check the disease severity and stage relationship to clinical staging. They concluded that bands are common at the posterior region in temperate cases of OSF and are more likely to also be found anteriorly as the disease increases in severity and stage relationship to clinical staging. The research was categorized clinically and functionally into three stages i.e, 1, 2, 3, and A, B, C. 

Clinically	Stage 1	Stage 2	Stage 3
	Faucial[1] bands only	Faucial and buccal[2] bands	Faucial and labial[3] bands
Functionally	Stage A	Stage B	Stage C
Mouth opening	13 - 20mm	10-12mm	<10mm

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^[1] Way from the back of the mouth to the pharynx

^[2] Surface of the tooth, opposite the cheek

^[3] Side of the tooth adjacent inside the cheek

They concluded that bands are common at the posterior region in temperate cases of OSF and are more likely to also be found anteriorly as the disease increases in severity.

DISEASE BURDEN/PREVALENCE

The worldwide prevalence of OSF is estimated to be 2.5 million. India has a high rate because of widespread tobacco and areca nut products with a ratio of 0.2-2.3% in males and 1.3-4.6% in females and the age range vary between 11 to 60 years [3]. Many studies found no severity of OSF in Pakistan. However, non-probability cross-sectional research showed 43.1% of cases of OSF and the majority were of women from 15-30 years age group. The reasons were chewing habits of areca nut, betal with tobacco, and without tobacco and naswar which initiated in the childhood of lower-class families [5].   

Fig 2: Map showing prevalence rate globally and in India.

RISK FACTORS

Ingestion of chilies, nutritional deficiencies, genetic, immunologic processes, areca nut chewing, naswar chewing, consumption of pan, and gutka are common risk factors of OSF [6]. Many researchers show that protein, vitamins, and iron deficiencies are commonly found in OSF patients. Immunological factors have been seen as an autoimmune basis, for instance, HLA, DR7, and DR3 antigen presence found whereas antibodies led towards the thyroid gland and antinuclear antibodies. A research conducted on the Indian population concluded that the relationship between copper and OSF is linked to the excess copper amount in tissues of fibrotic diseases such as cirrhosis.

MECHANISM OF DISEASE

OSF mostly impacts the oral cavity, the upper third of the esophagus, and pharynx. Molecular studies currently establish a model of transforming growth factor-B in the sense of regulation by areca nut. This is also a collagen-based disorder. When collagen synthesis is increased procollagen gene activates, proteinase levels elevate and lysyl oxidase regulates upward. In the case of collagen degradation tissue inhibitor genes (TIMPs) are activated which inhibit activated collagen and further collagenase activity automatically decreases. Studies also recommended proinflammatory cytokines involvement dysregulated by largely areca nut chewing. In other words, it is said that it oxidatively damages the cells.

RECENT ADVANCES

Human-based research must be provided for better understanding to reduce clearly OSF disorder than animal models. Recently, scientists are trying to cure OSF by using molecular markers.

CONCLUSION

In-detail further research is required especially in the case of copper incorporation and transformation of factor-B. A disease with a high prevalence of geographically in Asia maybe treated nothing but by using drugs. 

By: Maryam Akram

References:

1.     Deepak, P., Prateek, B., Dhurv, K., Deepak, C., Mansi, A., & Yoshi, P. (2017). Oral submucous fibrosis: newer proposed classification with critical updates in pathogenesis and management strategies. National Journal of Maxillofacial Surgery, 8(2): 89 - 94.  

2.     Dr. Chandramani, B.M., Dr. Palak, H.S., Naman, R.K.R., & Dr. Ruchi, K.P. (2015). Oral submucous fibrosis: an overview with evidence based management. International journal of oral health sciences and advances, 3(3).

3.     Naman, R.R., Alessandro, V., Chandramani, B.M., Ruwan, D, J., Alexander, R.K., & Newell, W.J. (2020). Oral submucous fibrosis: a contemporary narrative review with a proposed inter-professional approach for an early diagnosis and clinical management. Journal of otolaryngology - head & neck surgery, 49(3).  

4.     Shivakumar, G.G., & Sahana, S. (2011). Clinical staging of oral submucous fibrosis: a review. International journal oral medical science, 10(3):216-219.

5.     Sidra, M., Nazish, F., Salim, H., & Mervyn, H. (2016). High risk of malignant transformation of oral submucous fibrosis in pakistani females: a potential national disaster. Journal of the Pakistan medical association JPMA, 66(11).  

6.     Shridevi, A., Amol, K., Kaushal, S., Raghavendra, A., Samruddhim M., & Dr. Umesh. (2017). Assessing risk factors for oral submucous fibrosis - a cross-sectional survey. International journal of current medical and pharmaceutical research, 3(2), pp: 1297-1299.

7.     Paturu, K., Ila, P., & Imran, K. (2019). Molecular pathways regulated by areca nuts in the etiopathogenesis of oral submucous fibrosis. US national library of medicine, review article, 80(1): 213 - 224.

8.     Saba, K., Laxmikanth, C., Shenal, K. P., Veena, K.M., & Prasanna, K. (2012). Pathogenesis of oral submucous fibrosis. Journal of cancer research and therapeutics, 8(2).

9.     Prageet, K. S., Jeanne, F. G., Natasha, B., & Namrata, S. (2018). Internal journal of dentistry, volume 2018. Article ID 242087.

10.  Table and graph are created by author, so no reference was needed to add.