Incidence Of Oral Submucous Fibrosis Research Articles

English

A common oral disease named as oral submucous fibrosis (OSMF) has the tendency to usually affect many areas of the oral cavity as well as involving the area of pharynx. The characteristic feature of oral submucous fibrosis is the fibrosis in submucosal area which involves maximum part of oral cavity leading to advanced lock jaw as a result of rigidity in cheeks, pharynx, lips and upper third part of the oesophageal canal progressing to dysphagia. It has been reported that OSMF occurs mainly in persons who are habituated to chew areca nut or products containing areca nut along with other ingredients. In recent years with the introduction of commercially available Gutka and other areca nut products, the incidence of OSMF is increasing especially in the younger generations. OSMF is irreversible and persists even after cessation of chewing habit and the severity increases along with the duration of habit. In 2007, the categorization of oral submucous fibrosis was done as a premalignant condition by WHO and it has higher chances of malignant transformation. Early diagnosis and application of proper treatment modality is mandatory to reduce morbidity and mortality rate. There are many classification systems that have been proposed in literature for oral submucous fibrosis, among which many are based on clinical features, some of them on functional aspects and others are based on histopathological aspects. Here is an attempt to enlighten the facts and recent updates of clinical, functional, histopathological features as well as pathogenesis and management of oral submucous fibrosis. The complete knowledge of oral submucous fibrosis is a useful to the clinicians as well as academicians and researchers for timely detection and proper management of the disease. KEY WORDS Oral Submucous Fibrosis, Precancerous Lesions, Precancerous Conditions, Sclerosing Stomatitis

Detoxification of 1,2-dihydroxy- 4-allylbenzene, a major phenolic compound in Piper betle, through glucuronidation using S9 protein of rat liver (Sprague Dawley)

1,2-dihydroxy- 4-allylbenzene (DHAB) is a major compound in Piper betle leaf and also a metabolite of safrole metabolism. Epidemilogic studies showed people who have betel quid chewing habit are related to the incidence of oral submucous fibrosis and/or tumor formation. The aims of this research was to study the detoxification through the glucuronidation of DHAB using S9 protein of male rat liver ( Sprague Dawley) and a co-factor of uridin 5′-diphosphoglucuronide acid (UDPGA). The results showed that glucuronidation of DHAB using S9 protein of rat liver resulted two isomers of glucuronide metabolites due to the availibility of two active hydroxyl groups that one of them can bind glucuronide but not two of hydroxyl at the same time.

Salivary pooling: is it specific to particular regions in oral submucous fibrosis?

Despite extensive research, the pathophysiology of oral submucous fibrosis (OSMF), a premalignant condition that primarily affects the mucosa, is still unclear, although the chewing of areca nut is known to be the primary cause. While a clear association exists between areca nut and OSMF, very little has been published on the reason for its sporadic incidence in the mouth. Many authors have suggested the site where quid is habitually placed, but this fails to explain multiple sites in those who chew on one side. We hypothesised that the pattern of salivary pooling might affect the distribution of OSMF by carrying the chemicals responsible for mucosal damage. In our study of 174 patients, we evaluated the sites where quid was habitually placed and the areas of salivary pooling, and their association with the incidence of OSMF. Most chewers (136/174, 78%) placed the quid in the buccal vestibule, although other sites were also used including the vestibule of the lip, tongue, and floor of the mouth. The standardised residuals suggested significant associations (p<0.001) between salivary pooling and OSMF, and indicated that salivary pooling affects the mucosal surfaces where it occurs. Our results show that the quid is not the only cause of OSMF. Salivary pooling also has an important role and provides a possible mechanism for the sporadic incidence of the condition. To our knowledge this is the first study to evaluate salivary pooling as a contributory factor in OSMF, and it may help to explain the pattern of distribution. Further work is needed in this area to understand the association more fully.

Translational approach utilizing COX-2, p53, and MDM2 expressions in malignant transformation of oral submucous fibrosis.

About 20% of the world's population uses some form of betel nut, which suggests that the incidence of oral submucous fibrosis (OSF) is higher than current estimates. OSF has the potential to undergo malignant transformation; thus, there is a need to identify relevant markers to assess its aggressiveness. We evaluated changes in COX-2, p53, and MDM2 expressions in progressive OSF. Expressions of COX-2, p53, and MDM2 increased with OSF progression. There was a strong association between COX-2 overexpression and recurrence of oral squamous cell carcinoma (P < 0.001) and a positive relation between increased MDM2 expression and failure of radiotherapy (P = 0.007). These findings suggest that COX-2 is an important marker of disease progression and that MDM2 expression is useful for treatment planning.

Oral squamous cell carcinoma arising in background of oral submucous fibrosis: a clinicopathologically distinct disease

Oral cancer is the most common cancer in Indian males and is the third most common cancer in Indian females. Tobacco, alcohol, areca nut, and human papillomavirus (HPV) are the common etiologic factors. Each of these agents follows a unique model of carcinogenesis that leads to a certain distinct presentation and behavior. For example, HPV is strongly associated with oropharyngeal cancers in younger age and is known to have a better outcome and specific histopathologic characteristics. A high incidence of oral submucous fibrosis (OSMF) is linked to areca nut (group 1 human carcinogen) chewing in the Indian subcontinent. We prospectively studied 371 consecutive patients with proven squamous cell carcinoma of the oral cavity. Of these, 112 patients had oral cancer with OSMF and 259 had oral cancer without OSMF. All patients underwent standard management and their clinicopathologic findings were recorded. We found that patients of oral cancer with OSMF are younger males with better prognostic factors such as better grade of tumor differentiation, lesser incidence of nodal metastases, and extracapsular spread. This difference was maintained even after matching for stage. We also report that presence of OSMF is an independent factor influencing nodal metastases. Based on these findings we propose that oral cancers with OSMF constitute a clinicopathologically distinct disease. Since all patients with OSMF had chewed areca nut with or without smokeless tobacco, we believe that the differences in the 2 groups emanate from differential mechanisms of areca nut carcinogenesis.

Effect of α-tocopherol on salivary reactive oxygen species and trace elements in oral submucous fibrosis

Oral submucous fibrosis (OSMF) is a chronic debilitating disease and a well-recognized, potentially malignant condition of the oral cavity associated with betel quid chewing. Betel quid chewing is a popular oral habit in India and shows strong association in the incidence of OSMF. The objective of the study was to determine the levels of trace elements, pro-oxidants and reactive oxygen species (ROS) in saliva of betel quid chewers and OSMF patients, which may help in the diagnosis of cancer progression in the oral cavity. A total of 35 cases of OSMF and 35 cases of healthy individuals were included in the present study. The salivary status of ROS, pro-oxidants and some trace elements was studied in OSMF patients and normal healthy individuals. The levels of lipid peroxides (P < 0.001), conjugated dienes (P < 0.01), hydroxyl radicals (P < 0.01), superoxide dismutase (P < 0.05), copper (P < 0.05), calcium (P < 0.01), magnesium (NS), potassium (P < 0.05) and iron (P < 0.05) in OSMF patients were elevated when compared with normal healthy individuals. The levels of hydrogen peroxide (P < 0.05) and sodium (P < 0.01) in OSMF patients were found to be decreased when compared with control subjects. A significant alteration was noticed after supplementing with α-tocopherol in oral precancerous patients. These parameters may help in the detection of the severity of oral diseases.

Excision of Oral Submucous Fibrosis and Reconstruction with Full Thickness Skin Graft: A Case Study and Review of the Literature

Oral submucous fibrosis is a chronic debilitating disease characterized by gradually increasing fibrosis of the oral cavity and pharynx, mainly the buccal mucosa, resulting in trismus. The highest incidence of oral submucous fibrosis is seen in South India due to various deleterious habits. In spite of the numerous medical modalities employed in the management of oral submucous fibrosis, occasionally surgical intervention becomes inevitable. Various surgical approaches have been used to reconstruct the surgical defects following excision of fibrous bands. Full thickness skin grafts have been described in the literature with variable outcomes. In the present study a 38-year-old male presented with severe oral submucous fibrosis of the buccal mucosa, which was successfully treated and reconstructed using full thickness skin graft with stable functional result after one year of treatment. An integrated review of the literature regarding etiology, histopathology, diagnostic, and treatment modalities of the disease follows.

Tympanometric study of eustachian tube function in oral submucous fibrosis

Background: Oral submucous fibrosis (OSMF) is a premalignant condition. Incidence of OSMF in India is 0.5%, mainly found in southern states and also in Saurashtra region. The pathological changes can involve mucosa, submucosa and the underlying muscles. The changes of tubal and paratubal muscles can affect the eustachian tube function. So, this study was carried out with an aim to determine the effect of OSMF on the eustachian tube function. Materials and Methods: 54 ears of 27 patients with OSMF and 50 ears of 25 normal persons were screened by eustachian tube function test (ETFT) after thorough history taking and clinical examination. Results: Out of the 54 ears in the OSMF group, type A curve was obtained in 42 (77.8%) ears, type B curve in none and type C curve was found in 12 (22.2%) ears, as compared to the normal group in which type A curve was obtained in 46 (92%) ears, type B curve in 2 (4%) ears, type C curve was found in 2 (4%) ears. On testing compliance of the middle ear, no change was observed at -200 daPa in 15 (27.8%) ears in the OSMF group and 5 (10%) ears in the normal group. Conclusion: The data observed were statistically analyzed by chi-square test, which suggested significant association between OSMF and eustachian tube function. Therefore, it can be concluded that eustachian tube function may be affected in OSMF and vice versa. So, while treating OSMF, hearing disability due to eustachian dysfunction has to be kept in mind and vice versa because treatment of hearing disability without taking care of OSMF will not be successful.

Oral Submucous Fibrosis - A changing scenario

Tobacco causes a wide spectrum of diseases. Its use is the world's leading cause of death accounting for four million deaths per year. There is a general concept among the younger generation that chewing tobacco (spit tobacco, smokeless tobacco) is safe or less harmful than smoking, which has led to an increase in tobacco chewing habit. Chewable tobacco is a greater health hazard having 24 - 30% higher tobacco content. In addition to oral cancer chewing tobacco leads to impaired functions of heart, nerves, brain and altered hormonal activities. Users of manufactured tobacco products like gutkha, pan parag etc. also present with an increasing incidence of oral submucous fibrosis; of concern is that this is of early onset. In this context patients coming to the OP clinic of Oral Medicine and Radiology, Dental College, Trivandrum were screened for OSF during the period Jan 2003 - Oct 2003. The clinical presentation of OSF in patients using these manufactured smokeless tobacco products or Betel quid spices was documented and were compared with the results of a similar study conducted in the department during the period May 1993 to Feb 1994.

Oral Sub‐mucous fibrosis (OSMF): a study of associated habits and their impact

Objective. To determine the incidence of associated habits in patients with OSMF. The relationship between the different habits and the severity of the disease.Design. Cross‐sectional Survey.Setting. Tertiary Referral Centre.Participants. Adult patients with OSMF.Outcomes Measured. (1) Association of different habits with OSMF. (2) Duration of chewing before onset of symptoms related to OSMF. (3) Severity of OSMF with respect to different chewing habits.Results. A total of 500 patients with OSMF were included in this study over 2‐year period. Except 3 patients (0.6%) rest all gave history of one of these chewing habits–(Pan‐Masala is a mixture of Arecnuts, Lime, Catechu and undisclosed sweetening and Flavouring agents). 432 (86.4%) of Pan‐Masala with Tobacco, 56 (11.2%) of only Tobacco, 8 (1.6%) of only Betel Nut, 1 (0.2%) of pan‐Masala without Tobacco. Smoking Tobacco had no statistically significant effect on the incidence of OSMF in any of these groups. In the above mentioned order the other associated factors were respectively. The mean duration of chewing before onset of symptoms in years 3.28, 3.95, 8.37 and 10. The proportion of patients with &lt;2 finger mouth opening was 249/432 (57.63%), 28/56 (50%), 3/8 (37.5%), 0 (0%).Conclusion. The occurrence of OSMF is strongly associated with the habit of chewing Pan‐Masala with Tobacco and less so with only Tobacco or Betel Nut. Patients consuming Pan‐Masala with Tobacco develop this disease earlier then chewers of Tobacco and Betel Nut. Restriction of mouth opening is worst with Pan‐Masala with Tobacco.References 1 Ariyawardana A., Athukorala A.D., Arulanandam A. (2006) Effect of betel chewing, tobacco smoking and alcohol consumption on oral sub‐mucous fibrosis: a case‐control study in Sri Lanka. J Oral Path &amp; Med35, 197–2012 Ranganathan K., Devi M.U., Joshua E., Kirankumar K., Saraswathi T.R. (2004) Oral sub‐mucous fibrosis: a case‐control study in Chennai, South India. J Oral Path &amp; Med33, 274–277

Prolonged exposure to arecoline arrested human KB epithelial cell growth: Regulatory mechanisms of cell cycle and apoptosis

Arecoline, the main areca alkaloid in betel quid (BQ), is reported to have cytotoxic, genotoxic, and mutagenic effects in various cells. It shows strong correlation to the incidence of oral submucous fibrosis, leukoplakia, and oral cancer. To clarify the role of arecoline in BQ-induced carcinogenesis, primary human gingival keratinocyes (GK) and human KB epithelial cells were used for studying the molecular mechanisms of arecoline-mediated cell cycle deregulation for comparison. After 24 h of exposure, arecoline (0.2–0.8 mM) inhibited KB cell growth in a dose- and time-dependent manner with a reduction in cell number by 27–37 and 37–58%, respectively, as determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. Incubation of KB cells with arecoline (0.1–0.4 mM) caused late-S and G2/M phases’ cell cycle arrest. Western blot analysis revealed that arecoline induced cyclin Bl, Wee 1, and phosphorylated cdc2 protein levels whereas it declined p21 protein expression in KB cancer cells. Nevertheless, arecoline induced p21, but decreased cdc2 and cyclin B1 protein levels in GK. We demonstrated that higher concentrations of arecoline (0.2–1.2 mM) induced both cell necrosis and apoptosis as detected by DNA fragmentation and Annexin V–PI staining after long-term (48 h) treatment. Our results suggest that differential regulation of S and/or G2/M cell cycle-related proteins in the GK and KB cells play a crucial role in different stages of BQ-mediated carcinogenesis.

Alert for an epidemic of oral cancer due to use of the betel quid substitutes gutkha and pan masala: a review of agents and causative mechanisms.

In south-east Asia, Taiwan and Papua New Guinea, smoking, alcohol consumption and chewing of betel quid with or without tobacco or areca nut with or without tobacco are the predominant causes of oral cancer. In most areas, betel quid consists of a mixture of areca nut, slaked lime, catechu and several condiments according to taste, wrapped in a betel leaf. Almost all habitual chewers use tobacco with or without the betel quid. In the last few decades, small, attractive and inexpensive sachets of betel quid substitutes have become widely available. Aggressively advertised and marketed, often claimed to be safer products, they are consumed by the very young and old alike, particularly in India, but also among migrant populations from these areas world wide. The product is basically a flavoured and sweetened dry mixture of areca nut, catechu and slaked lime with tobacco (gutkha) or without tobacco (pan masala). These products have been strongly implicated in the recent increase in the incidence of oral submucous fibrosis, especially in the very young, even after a short period of use. This precancerous lesion, which has a high rate of malignant transformation, is extremely debilitating and has no known cure. The use of tobacco with lime, betel quid with tobacco, betel quid without tobacco and areca nut have been classified as carcinogenic to humans. As gutkha and pan masala are mixtures of several of these ingredients, their carcinogenic affect can be surmised. We review evidence that strongly supports causative mechanisms for genotoxicity and carcinogenicity of these substitute products. Although some recent curbs have been put on the manufacture and sale of these products, urgent action is needed to permanently ban gutkha and pan masala, together with the other established oral cancer-causing tobacco products. Further, education to reduce or eliminate home-made preparations needs to be accelerated.

Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells.

Betel quid (BQ) chewing shows a strong correlation to the incidence of oral submucous fibrosis (OSF), leukoplakia and oral cancer. BQ contains mainly areca nut, lime, Piper betle leaf (PBL) and the inflorescence of P. betle (IPB). Hydroxychavicol (4-allyl-catechol, HC), as a major phenolic compound in PBL and IPB, is shown to induce oxidative stress, glutathione (GSH) depletion and cell cycle deregulation. Using bivariate BrdU/PI flow cytometry, KB cells in DNA synthesis (S phase) are shown to be sensitive to the toxic effect of HC and show cell cycle arrest and apoptosis following exposure to 0.1 and 0.3 mM HC. HC-induced apoptosis and cell cycle arrest are associated with mitochondrial membrane potential (delta Psim) depolarization as revealed by a decrease in rhodamine fluorescence. N-acetyl-L-cysteine (1 mM), superoxide dismutase (100 U/ml) and catalase (1000 U/ml) were effective in prevention of HC-induced GSH depletion (as indicated by chloromethylfluorescein fluorescence), reactive oxygen species (ROS) production (by dichlorofluorescein fluorescence), cell cycle arrest and apoptosis. However, dimethylthiourea (2 mM), neocuproine (1 mM), 1,10-phenanthroline (200 microM) and desferrioxamine (0.5 mM) showed little effect on HC-induced cell changes. HC elevated the cellular and mitochondrial GSH levels at moderate concentrations (0.05-0.1 mM), whereas at a concentration of 0.3 mM, inhibitory effects were noted. These results indicate that HC consumption may be associated with BQ-chewing-related oral mucosal diseases via GSH depletion, ROS production, mitochondrial dysfunction, cell cycle disturbance and the induction of apoptosis. These events are related to the production of superoxide radicals and hydrogen peroxide.

Co-expression of colligin and collagen in oral submucous fibrosis: plausible role in pathogenesis.

The high incidence of oral submucous fibrosis (OSF), a potentially malignant condition of the oral cavity, in the Indian subcontinent is causally associated with commonly prevailing habit of chewing areca nut and tobacco. Knowledge of molecular alterations in OSF is meagre. OSF is characterised by progressive accumulation of collagen fibres in lamina propria and oral submucosa. Colligin/HSP47 is a 47KDa stress protein which acts as a chaperone for collagen. We hypothesized that since colligin plays a vital role in folding and assembling collagen it may be involved in the pathogenesis of OSF. The present study was undertaken in tobacco and areca nut chewing Indian OSF patients to investigate the correlation, if any, between the expression of colligin and collagen type I proteins in OSF lesions. Immunohistochemical analysis showed overexpression of colligin and collagen type I proteins in 16/23 (70%) and 15/23 (65%) of OSF cases, respectively. The hallmark of the study was the significant association between the increased expression of type I collagen and its chaperone, colligin, in OSF lesions (P=0.0494). The data suggest that the increased levels of colligin in OSF may contribute to the deposition of collagen and consequent increased fibrosis in the oral submucosa in OSF lesions.

Effect on the incidence of oral submucous fibrosis of intervention in the areca nut chewing habit

Incidence of oral submucous fibrosis was calculated from a 10-yr prospective intervention study of 12,212 individuals with a strong component of health education on tobacco and area nut chewing. Based on 11 new cases among 6341 chewers, the annual incidence was 8.0 per 100,000 among men and 29.0 for women. An earlier 10-yr follow-up study, with no intervention component, served as control. Based on 11 new cases among 3,809 chewers, the annual incidence was 21.3 per 100,000 for men and 45.7 for women controls. Although the decrease in the incidence in the intervention cohort was not statistically significant due to small number of cases, the results underscored the causal role of areca nut chewing and indicated the potential for primary prevention of oral submucous fibrosis.

“MISI” an etiologic factor in oral submucous fibrosis

The incidence of oral submucous fibrosis is high in Eastern Uttar Pradesh. The females were found affected four times more frequently than the males. ‘Misi’ was found to be the main causative factor among them. The chemicals in this substance, are a source of constant irritation. The use of ‘Misi’ should be discouraged as a preventive measure.