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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 28  |  Issue : 2  |  Page : 111-118

The clinicohistopathologic study of oral submucous fibrosis: A new staging system with treatment strategies


Department of Oral Medicine and Radiology, Ahmedabad Dental College and Hospital, Gandhinagar, Gujarat, India

Date of Submission31-Mar-2015
Date of Acceptance16-Nov-2016
Date of Web Publication02-Dec-2016

Correspondence Address:
Yesha V Jani
M 10/74 Swatantra Senani Flats, Near Pragatinagar, Naranpura, Ahmedabad - 380 013
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-1363.195082

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   Abstract 

Introduction: Oral submucous fibrosis (OSMF), a precancerous condition, is highly prevalent in the Indian subcontinent. The current classification systems focus on either clinical and/or histopathologic features; hence, a need has arisen to formulate a staging system with emphasis on treatment strategies. Aims and Objectives: The objective of the study was to devise the staging system which is suggestive of treatment strategies based on the clinical and histopathological staging. Study Design: The study sample consisted of 100 OSMF patients categorized into clinical stages of Andrade and Khanna's staging system and histological grading of Andrade and Khanna's grading system. Thereafter, clinical features were reevaluated for modifying the Andrade and Khanna's staging system. Results: Based on the findings of the current study, certain clinical features were modified among all the stages of Andrade and Khanna's classification system for OSMF. Conclusion: The present study has devised a new staging system for OSMF with objective clinical and histopathological criteria which provide guidance for treatment plan.

Keywords: Classification, oral submucous fibrosis, precancerous condition


How to cite this article:
Jani YV, Dudhia BB. The clinicohistopathologic study of oral submucous fibrosis: A new staging system with treatment strategies. J Indian Acad Oral Med Radiol 2016;28:111-8

How to cite this URL:
Jani YV, Dudhia BB. The clinicohistopathologic study of oral submucous fibrosis: A new staging system with treatment strategies. J Indian Acad Oral Med Radiol [serial online] 2016 [cited 2021 Apr 13];28:111-8. Available from: https://www.jiaomr.in/text.asp?2016/28/2/111/195082


   Introduction Top


Oral submucous fibrosis (OSMF) is a chronic, precancerous condition found to affect the South and South East Asian population, especially those of the Indian subcontinent. [1],[2],[3],[4],[5],[6],[7] It has now become an Indian epidemic with an estimated 2.5 million people being affected with this disease. [8],[9]

It has been suggested that areca nut chewing, consumption of chillies, genetic susceptibility, nutritional deficiency, autoimmunity and collagen disorders may be involved in the pathogenesis of this condition. The most common etiology considered for causation of OSMF is "arecoline" which is a constituent of arecanut. [1],[4],[5],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18]

In the early cases of OSMF, oral mucosa becomes blanched and slightly opaque. [10],[19],[20],[21] Fibrosis of mucosa occurs in the late cases of OSMF; leading to stiffness seen most commonly in the palate, buccal mucosa and faucial pillars. Progression of fibrosis leads to difficulty in opening the mouth, inability to whistle or blow out a candle, and sometimes difficulty in swallowing. [4],[10],[19],[20]

Histopathological findings in early cases of OSMF can be listed as epithelial hyperplasia, thickened collagen bundles, moderate numbers of large fibroblasts and inflammatory cell infiltration containing a number of polymorphonuclear leukocytes. [9],[12] The advanced cases of OSMF show histopathological features such as epithelial atrophy, dense bundles and sheets of collagen, thick bands of subepithelial hyalinization extending into the submucosal tissues (replacing fat or fibrovascular tissue), decreased vascularity, absence of edema and decreased inflammatory cells (lymphocytes and plasma cells). [9],[10],[12],[19],[20],[22]

OSMF is a well-recognized, potentially premalignant condition. Malignant transformation rate as high as 7.6% has been reported from the Indian subcontinent over a 17-year period. [5],[6],[8],[9],[12],[23],[24],[25],[26],[27],[28],[29]

Hence, the treatment of patients with OSMF depends on the degree of clinical involvement which, in turn, depicts changes taking place at the microscopic level. The treatment should be initiated as reducing exposure to the risk factors. Submucosal injections of agents such as steroids, hyaluronidase, placental extracts and collagenase have been tried with limited benefits. [10],[20],[30],[31],[32],[33],[34] Excision of the fibrous bands, with correction of the defect using various grafts, especially with buccal fat pad graft, has been tried in patients with severe OSMF. [30],[35],[36] Even though several treatment regimens have been tried, there is no treatment which offers a complete cure for OSMF, and the condition is irreversible, once the fibrosis sets in. [4],[34],[37]

OSMF is being studied since many years for its clinical and histopathological staging. All the studies have suggested different clinical staging of OSMF (based on the severity of clinical features) and different histopathological grading (based on tissue involvement). Several classifications have been proposed by various researchers based on different clinical aspects of OSMF for clinical staging.

The current staging systems fail to suggest a correlation between clinical and histopathological staging of OSMF. Hence, a new system must be introduced that correlates both the clinical and histopathological stages. A system like this could help in targeting the treatment of patients based on the stage of the disease. The purpose of this study is to formulate such a classification system.


   Materials and Methods Top


The study sample consisted of 100 OSMF patients coming to the Oral Medicine and Radiology department of the institute. The patients who were habitual of eating spicy food and/or chewing areca nut/tobacco in addition to having examined for two or more of the following signs and symptoms suggestive of OSMF were included in the study:

  1. Burning sensation and difficulty in eating hot and spicy food
  2. Reduced mouth opening
  3. Blanched or opaque appearance of the mucosa
Participants were then interviewed and the history findings were recorded in a case sheet proforma specially prepared for the study. A detailed history regarding the type, frequency and duration of habit was obtained followed by thorough clinical examination of various mucosae and salivation performed by the principal investigator. The clinical staging was done by observer A from the Oral Medicine and Radiology department by evaluating the clinical findings as per the criteria of Andrade and Khanna's staging system, [38] which depends upon the severity of clinical features.

After clinical examination and staging, a punch biopsy was taken by the principal investigator from the buccal mucosa [Figure 1] and [Figure 2], and the tissue was sent to the department of Oral Pathology of the institute for detailed histopathological examination. The study has been conducted as per the IRB guidelines and Helsinki Declaration and after approval from the ethical committee of the institute. Histological grading was done by observer B from the Oral Pathology department as per the criteria of Khanna and Andrade [38] grading system, which depends upon the involvement of epithelium (keratinization and thickness) as well as connective tissue (hyalinization, fibrous tissue, fibroblasts, blood vessels, and inflammatory cells). Observers A and B were unknown of each other's findings to avoid any bias. Epithelial atypia in form of mild to severe dysplasia was summarized according to the criteria by Krammer.
Figure 1: Photograph showing armamentarium used for taking punch biopsy

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Figure 2: Photograph showing procedure of taking punch biopsy from buccal mucosa

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After histopathological grading was done, clinical and histopathological features were studied and reevaluated. Then, the criteria of Andrade and Khanna's staging system were modified by addition of certain clinical features in each clinical grade while retaining the Khanna and Andrade histopathological grading as a confirmatory gold standard. Patients were then advised the treatment according to the new staging system.


   Results Top


[Table 1] demonstrates clinical features incorporated in clinical stage I. All patients had burning sensation on consuming hot and spicy food, normal tongue protrusion, and no palpable fibrous bands. Blanching of faucial pillars, soft palate and buccal mucosa was seen in 75% of the patients. Acute ulceration and recurrent stomatitis was seen in 25% of the patients whereas none of the patients had hypersalivation.
Table 1: Patients having clinical features of clinical stage I (out of 4 clinical stage I patients)


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[Table 2] demonstrates clinical features incorporated in clinical stage II. Most of the patients had burning sensation on eating normal food, blanching of faucial pillars, soft palate, buccal mucosa and labial mucosa as well as mouth opening reduced by one-third (25-38 mm) with palpable fibrous bands in the faucial pillars, palate and buccal mucosa. Very few patients had reduced salivation, reduced tongue protrusion, lymphadenopathy or ulcerative lesions. None of the patients had mottled appearance in buccal mucosa or red erythematous patches.
Table 2: Patients having clinical features of clinical stage II (out of 36 stage II patients)


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[Table 3] demonstrates clinical features incorporated in clinical stage III. All the patients had severe blanching, palpable fibrous bands in the faucial pillars, palate, buccal mucosa and labial mucosa which radiate to pterygomandibular raphe and soft palate. Almost all patients had mouth opening reduced by two-third (20-30 mm), reduced tongue protrusion and severe burning sensation on eating normal food whereas a very small number of patients had atrophy of lips, hyposalivation, lymphadenopathy and inability to blow cheeks.
Table 3: Patients having clinical features of clinical stage III (out of 44 stage III patients)


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[Table 4] demonstrates clinical features incorporated in clinical stage IV. All the patients had reduced mouth opening up to 15-25 mm, severe blanching, as well as widespread fibrosis involving the faucial pillars, palate, buccal mucosa, labial mucosa, and floor of the mouth, reduced palatal movements, and shrunken and fibrotic uvula. Almost all patients had restricted tongue movements, papillary atrophy of tongue, and severe burning sensation even in absence of stimuli. Very few patients had hyposalivation and lymphadenopathy.{Table 3}
Table 4: Patients having clinical features of clinical stage IV (out of 16 stage IV patients)


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[Table 5] demonstrates the distribution of different histological features among OSMF patients. Histological features were categorized into epithelial changes and connective tissue changes. The most common feature observed in epithelium was atrophic epithelium in 80% patients followed by parakeratinization in 70% patients, absence of retepegs, and less prominence of retepegs in 53 and 44% patients, respectively. Epithelial dysplasia was observed in 63% patients, out of which mild dysplasia was observed in maximum i.e., 40% patients, followed by moderate dysplasia and severe dysplasia observed in 22 and 1% patients, respectively. The most common features observed in connective tissue were chronic inflammatory cell infiltrate in 87% patients, dense fibrous connective tissue in 65% patients, and partial hyalinization of collagen fibers in 61% patients. Other common features observed in connective tissue were dilated blood vessels and decreased number of fibroblasts in 42 and 62% patients, respectively.
Table 5: Distribution of different histological features as per Khanna and Andrade`s criteria among OSMF patients with different histological grades


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[Table 6] demonstrates comparison between histological grading and clinical staging in OSMF patients. Out of 100 OSMF patients, 3 belonged to histological grade I, 34 belonged to histological grade II, 43 belonged to histological grade III, and 20 belonged to histological grade IV. Out of the 4 patients of clinical stage I, 3 (75%) patients belonged to histological grade I and 1 (25%) patient belonged to histological grade II. Out of the 36 patients of clinical stage II, 28 (77.8%) patients belonged to histological grade II, followed by 7 (19.4%) patients in grade III, and 1 (2.8%) patient in histological grade IV. Out of the 44 patients of clinical stage III, 33 (75%) patients belonged to histological grade III, followed by 6 (13.7%) patients in histological grade IV, and 5 (11.5%) patients in histological grade II. Out of the 16 patients of clinical stage IV, 13 (81.2%) patients belonged to histological grade IV, followed by 3 (18.8%) patients in histological grade III. Pearson's correlation test revealed that r value was 0.792.
Table 6: Comparison between clinical staging and histological grading in OSMF patients


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   Discussion Top


OSMF is a chronic, insidious, disabling condition of the oral mucosa characterized by epithelial atrophy and progressive accumulation of collagen fibers in the lamina propria and submucosa. [35],[39] OSMF is a potentially malignant disease of the oral cavity and is most commonly found in Asian countries. [22]

Because OSMF is considered a precancerous condition, it is essential to diagnose and treat as per the stage of the disease. At present, many staging systems exist, which categorize OSMF in different stages clinically and histologically.

Clinically OSMF is mostly categorized on the basis of the severity of clinical features. Lal (1953) was the first to categorize OSMF in different clinical stages on the basis of severity of clinical features. [22] The staging system lacks specificity of criteria and also lacks symptoms such as burning sensation and mouth opening. Criteria of the staging system are very subjective causing variability in staging the disease, thus, making it difficult to compare with the histological grades of the disease. Another clinical staging system was proposed by Pindborg et al. [19] where he studied 118 patients; 79 patients in group I, 29 patients in group II (A), 8 patients in group II (B), and 7 patients in group III. He gave clinical staging according to clinical features such as blanching, fibrosis, and precancerous lesions, however, it was subjective and not specifically related to the clinical features. It did not consider the alterations in the mouth opening (interincisal distance) of the patients, which is one of the important features of OSMF. Kiran et al. [5] proposed a functional staging system based only on mouth opening after examining 75 patients where 5 patients were from stage I, 57 patients from stage II, and 13 patients in stage III. Functional staging system has been divided in three stages which has ranges of mouth opening. Based on several studies, it is suggested that common clinical presentations of fibrosis and burning sensation along with the range of mouth opening would be more convenient and appropriate for the clinicians to diagnose and treat. Khanna and Andrade [14] gave both clinical and histological grading system for OSMF after evaluating 100 patients over a period of 6 years. These patients were grouped in four categories: group I-very early cases (3); group II - early cases (22); group III - moderately advanced cases (42); group IVa - advanced cases (25); and group IVb - advanced cases with premalignant changes and malignant transformation (8). Clinical staging system is based on clinical signs and symptoms, which includes burning sensation, mouth opening, and features of fibrosis. Although staging system does not have specifications for each stage, features are subjective to divide OSMF into different stages; thus, it becomes difficult to correlate it with the histological grades.

Histopathologically, OSMF is categorized on the basis of the involvement of the tissue and severity of the involvement. The first staging system based on histopathological features was proposed by Pindborg et al. [19] The staging system is not only based on the subepithelial collagen but also on the following criteria such as the presence or absence of edema, nature of collagen bundles, overall fibroblastic response, state of the blood vessels, and predominant cell type in the inflammatory exudates.

Khanna and Andrade [38] further divided OSMF based on modified Pindborg's criteria. The histological features are specific to distinguish between grades of OSMF. The changes of epithelium in OSMF cannot be overlooked as few research studies have stated that the epithelial changes are not necessarily secondary to connective tissue and this atrophic epithelium in OSMF is envisaged to predispose malignant transformation when exposed to oral carcinogens. In a recent study, Rajendra et al. [10] examined and qualified OSMF sections for the number, size, and density of vessels, and observed that mean vascular density was almost the same among the various OSMF cases and controls. This finding contradicts the above mentioned changes in the blood vessels in the classification.

The role of staging is important for the treatment plan as it is the ultimate goal. The usefulness of a staging system is that it helps in categorizing treatment options for the associated stage of the disease. Treatment can also be divided in four groups. In the present study, for establishing the new staging system, all histological findings were correlated as manifestations of the clinical signs and symptoms. The present study shows high correlation between both the staging system, clinical and histological.


   Conclusion Top


OSMF is a chronic insidious disease associated with areca nut chewing. It is a premalignant condition with a very high rate of malignant transformation, and hence its early diagnosis and treatment is mandatory. On the basis of the present study, histologic features can easily be categorized with the help of only clinical examination, thus, making proper treatment delivery easier and earlier [Table 7].
Table 7: Newer clinical and histopathological staging system for OSMF with accordingly suggested treatment


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Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Tupkari JV, Bhavthankar JD, Mandale MS. Oral submucous fibrosis (OSMF): A study of 101 cases. J Indian Acad Oral Med Radiol 2007;19:311-8.  Back to cited text no. 1
  Medknow Journal  
2.
Bose T, Balan A. Oral submucous fibrosis-A changing scenario. J Indian Acad Oral Med Radiol 2007;19:334-40.  Back to cited text no. 2
    
3.
Merchant AT, Haider SM, Fikree FF. Increased severity of oral submucous fibrosis in young Pakistani men. Br J Oral Maxillofac Surg 1997;35:284-7.  Back to cited text no. 3
    
4.
Ahmad MS, Ali SA, Ali AS, Chaubey KK. Epidemiological and etiological study of oral submucous fibrosis among gutkha chewers of Patna, Bihar, India. J Indian Soc Pedod Prev Dent 2006;24:84-9.  Back to cited text no. 4
[PUBMED]  Medknow Journal  
5.
Kiran Kumar K, Saraswathi TR, Ranganathan K, Uma Devi M, Elizabeth J. Oral submucous fibrosis: A clinico-histopathological study in Chennai. Indian J Dent Res 2007;18:106-11.  Back to cited text no. 5
    
6.
Tadakamadla J, Kumar S, Mamatha GP. Evaluation of serum copper and iron levels among oral submucous fibrosis patients. Med Oral Patol Oral Cir Bucal 2011;16:e870-3.  Back to cited text no. 6
    
7.
Shah N, Kumar R, Shah MK. Immunological studies in oral submucous fibrosis. Indian J Dent Res 1994;5:81-7.  Back to cited text no. 7
    
8.
Eipe N. The chewing of betel quid and oral submucous fibrosis and anaesthesia. Anesth Analg 2005;100:1210-3.  Back to cited text no. 8
    
9.
Pillai R, Balaram P, Reddiar KS. Pathogenesis of oral submucous fibrosis: Relationship to risk factors associated with oral cancer. Cancer 1992;69:2011-20.  Back to cited text no. 9
    
10.
Rajendran R. Oral submucous fibrosis. J Oral Maxillofac Pathol 2003;7:1-4.  Back to cited text no. 10
  Medknow Journal  
11.
Murti PR, Bhonsle RB, Gupta PC, Daftary DK, Pindborg JJ, Mehta FS. Etiology of oral submucous fibrosis with special reference to the role of areca nut chewing. J Oral Pathol Med 1995;24:145-52.  Back to cited text no. 11
    
12.
Canniff JP, Harvey W, Harris M. Oral submucous fibrosis: Its pathogenesis and management. Br Dent J 1986;160:429-34.  Back to cited text no. 12
    
13.
Mathew AL, Pai KM, Sholapurkar AA, Vengal M. The prevalence of oral mucosal lesions in patients visiting a dental school in Southern India. Indian J Dent Res 2008;19:99-103.  Back to cited text no. 13
[PUBMED]  Medknow Journal  
14.
Ranganathan K, Mishra G. An overview of classification schemes for oral submucous fibrosis. J Oral Maxillofac Pathol 2006;10:55-8.  Back to cited text no. 14
    
15.
Luqaman M, Vidya V. The role of serum copper and iron in oral submucous fibrosis. J Indian Acad Oral Med Radiol 2004;16:30-2.  Back to cited text no. 15
    
16.
Metkari S, Tupkari JV, Barpande SR. An estimation of serum malondialdehyde, superoxide dismutase and vitamin A in oral submucous fibrosis and its clinic-pathologic correlation. J Oral Maxillofac Pathol 2007;11:23-7.  Back to cited text no. 16
  Medknow Journal  
17.
Koshti S, Barpande S. Quantification of plasma fibrinogen degradation products in oral submucous fibrosis: A clinic-pathologic study. J Oral Maxillofac Pathol 2007;11:48-50.  Back to cited text no. 17
  Medknow Journal  
18.
Hayes PA. Oral submucous fibrosis in a 4-year-old girl. Oral Surg Oral Med Oral Pathol 1985;59:475-8.  Back to cited text no. 18
    
19.
Pindborg JJ, Odont, Sirsat M. Oral submucous fibrosis. Oral Surg Oral Med Oral Pathol Oral Radiol 1966;22:764-79.  Back to cited text no. 19
    
20.
Rajendran R. Oral submucous fibrosis: Etiology, pathogenesis, and future research. Bull World Health Organ 1994;72:985-96.  Back to cited text no. 20
    
21.
Zain RB, Ikeda N, Gupta PC, Warnakulasuriya S, van Wyk CW, Shrestha P, et al. Oral mucosal lesions associated with betel quid, areca nut and tobacco chewing habits: Consensus from a workshop held in Kuala lumpur, Malaysia. J Oral Pathol Med 1999;28:1-4.  Back to cited text no. 21
    
22.
Mani NJ, Singh B. Studies on oral submucous fibrosis. Oral Surg Oral Med Oral Pathol 1976;41:203-14.  Back to cited text no. 22
    
23.
Ghosh PK, Madhavi R, Guntur M, Ghosh R. Sister chromatid exchanges in patients with oral submucous fibrosis. Cancer Genet Cytogenet 1990;44:197-201.  Back to cited text no. 23
    
24.
Trivedy C, Meghji S, Warnakulasuriya KA, Johnson NW, Harris M. Copper stimulates human oral fibroblasts in vitro: A role in the pathogenesis of oral submucous fibrosis. J Oral Pathol Med 2001;30:465-70.  Back to cited text no. 24
    
25.
Aadha CD, Devi CSS. Studies on the hematological profile and trace elements in oral submucous fibrosis. J Clin Biochem Nut 1995;19:9-17.  Back to cited text no. 25
    
26.
Shettar SS, Mubeen. Estimation of serum Copper and Zinc levels in patients with oral submucous fibrosis. J Indian Acad Oral Med Radiol 2010;22:193-6.  Back to cited text no. 26
  Medknow Journal  
27.
Trivedy CR, Warnakulasuriya KS, Peters TJ, Senkus R, Hazarey VK, Johnson NW. Raised tissue copper levels in oral submucous fibrosis. J Oral Pathol Med 2000;29:241-8.  Back to cited text no. 27
    
28.
Shieh DH, Chiang LC, Shieh TY. Augmented mRNA expression of tissue inhibitor of metalloproteinase-1 in buccal mucosal fibroblasts by arecoline and safrole as a possible pathogenesis for oral submucous fibrosis. Oral Oncol 2003; 39:728-35.  Back to cited text no. 28
    
29.
Afroz N, Hasan SA, Naseem S. Oral submucous fibrosis: A distressing disease with malignant potential. Indian J Community Med 2006;31:270-1.  Back to cited text no. 29
  Medknow Journal  
30.
Le PV, Gornitsky M, Domanowski G. Oral stent as treatment adjunct for oral submucous fibrosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;81:148-50.  Back to cited text no. 30
    
31.
Sumanth KN, Ongole R, Rimal J. Efficacy of dexamethasone mucosal patch for oral submucous fibrosis (OSMF)-A pilot study. Int Poster J Dental Oral Med 2010;12:484.  Back to cited text no. 31
    
32.
Singh M, Niranjan HS, Mehrotra R, Sharma D, Gupta SC. Efficacy of hydrocortisone acetate/hyaluronidase vs. triamcinolone acetonide/hyaluronidase in the treatment of oral submucous fibrosis. Indian J Med Res 2010;131:665-9.  Back to cited text no. 32
[PUBMED]  Medknow Journal  
33.
Sankaranarayanan S, Ramachandran C, Padmanabhan J, Manjunath S, Baskar S, Senthil Kumar R, et al. Novel approach in the management of an oral premalignant condition-A case report. J Stem Cells Regen Med 2007;3:21.  Back to cited text no. 33
    
34.
Jirge V, Shashikanth MC, Ali IM, Anshum N. Levamisole and antioxidants in the management of oral submucous fibrosis comparative study. J Indian Acad Oral Med Radiol 2008;20:135-40.  Back to cited text no. 34
  Medknow Journal  
35.
Pandya S, Chaudhary AK, Singh M, Singh M, Mehrotra R. Correlation of histopathological diagnosis with habits and clinical findings in oral submucous fibrosis. Head Neck Oncol 2009;1:1-10.  Back to cited text no. 35
    
36.
Yeh CJ. Application of the buccal fat pad to the surgical treatment of oral submucous fibrosis. Int J Oral Maxillofac Surg 1996;25:130-3.  Back to cited text no. 36
    
37.
Kumar A, Bagewadi A, Keluskar V, Singh M. Efficacy of lycopene in the management of oral submucous fibrosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:207-13.  Back to cited text no. 37
    
38.
Khanna JN, Andrade NN. Oral submucous fibrosis: A new concept in surgical management. Int J Oral Maxillofac Surg 1995;24:433-9.  Back to cited text no. 38
    
39.
Taneja L, Anjana B, Vaishali K. Haemoglobin levels in patients with Oral Submucous Fibrosis. J Indian Acad Oral Med Radiol 2007;19:329-33.  Back to cited text no. 39
  Medknow Journal  


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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