Oral submucous fibrosis in India: a new epidemic?

BACKGROUND: Oral submucous fibrosis (OSF) is a precancerous condition caused by use of the areca nut. The reported prevalence of OSF in Bhavnagar district during 1967 was 0.16%. We investigated whether the impression of an increase in the incidence of the disease was real. METHODS: A house-to-house survey was conducted in Bhavnagar district, Gujarat state. The use of areca nut-containing products and tobacco was assessed through an interviewer administered questionnaire. The oral examination was done by dentists. The diagnostic criteria for OSF was the presence of palpable fibrous bands. RESULTS: A total of 11,262 men and 10,590 women aged 15 years and older were interviewed for their tobacco habits. Among 5018 men who reported the use of tobacco or areca nut, 164 were diagnosed as suffering from OSF. All but four cases were diagnosed among 1786 current areca nut users (age-adjusted relative risk: 60.6). Areca nut was used mostly in mawa, a mixture of tobacco, lime and areca nut, and 10.9% of mawa users had OSF (age-adjusted relative risk: 75.6). The disease as well as areca nut use was concentrated (about 85%) in the lower (< 35 years) age group. CONCLUSIONS: An increase in the prevalence of OSF, especially in the lower age groups, directly attributable to the use of areca nut products was observed. This could lead to an increase in the incidence of oral cancer in the future.

p53 expression in oral precancer as a marker for malignant potential.

The potential of p53 protein expression as a marker for determining which oral precancerous lesions may transform to malignancy with time was assessed. We compared the p53 expression in archival formalin-fixed, paraffin-embedded tissues from 22 baseline biopsies of precancerous lesions that transformed to cancer in 4-25 years against that in 68 similar lesions that did not transform over the same time period. Twenty-nine percent of precancers that transformed were p53-positive at baseline, compared to 31% of the biopsies that did not transform to malignancy. When examined by immunohistochemical methods p53 expression failed to detect potential malignant status of oral precancer. Non-specificity of the assay may account for this result but overexpression of p53 due to DNA damage by tobacco/betel-quid in non-progressive lesions needs further study. Nine precancerous lesions became p53-immunoreactive from precancer to cancer. This may suggest p53 overexpression peaks close to the time of transition from precancer to cancer rather than early in the natural history of oral precancer.

Etiology of oral submucous fibrosis with special reference to the role of areca nut chewing.

Oral submucous fibrosis (OSF) is a high risk precancerous condition, predominantly affecting Indians. Consumption of chilli was hypothesized as an etiologic factor on the basis of ecological observations and a solitary animal experimental study. Subsequent epidemiologic studies that included case-series reports, large cross-sectional surveys, case-control studies, cohort and intervention studies have identified areca nut as the major etiologic agent. Tissue-culture studies involving human fibroblasts, areca nut extracts and areca nut alkaloids supported this etiologic hypothesis by showing fibroblastic proliferation and increased collagen formation. Currently, the role of genetic susceptibility and that of autoimmunity are receiving attention. The influence of nutritional factors, if any, remains unclear.

A case-control study of oral submucous fibrosis with special reference to the etiologic role of areca nut.

A case-control study to elucidate the etiology of oral submucous fibrosis was conducted in Bhavnagar, Gujarat. Sixty consecutively arriving oral submucous fibrosis patients at a dental clinic were selected as cases. An equal number of controls matched for age, sex, religion and socioeconomic status were selected from individuals who did not exhibit any oral mucosal lesion or condition. Among cases, 98% chewed areca nut regularly in one form or the other whereas among controls 35% chewed areca nut, giving an overall relative risk of 109.6. Areca nut chewing was practiced most commonly in the form of mawa: a mixture containing mainly areca nut (over 90% by weight), some tobacco, and a few drops of lime. Mawa chewers and those who chewed mawa along with other chewing habits showed very high relative risks. The relative risks increased with increase in the frequency as well as the duration of chewing habits. In a bivariate analysis the effect of frequency and duration of chewing appeared to be multiplicative. The present findings confirm areca nut as the most important etiologic factor in oral submucous fibrosis.

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.

Regional variations in oral submucous fibrosis in India.

Regional variations in the characteristics of submucous fibrosis were studied in two districts in India. In Pune district this condition involved soft palate, uvula and retromolar areas significantly more often than in Ernakulam district. The tongue, floor of the mouth and the hard palate were not involved in Pune. The age of the patients in Pune district was lower than in Ernakulam district. Associated oral cancer, leukoplakia and petechiae were observed solely among patients in Ernakulam. The most important etiologic factor for submucous fibrosis is the chewing of areca nut, and in both areas studied all patients chewed areca nut. In Pune, cured areca nut without other ingredients was chewed by 66% and in Ernakulam, raw areca nut was chewed as an ingredient of pan with tobacco by 100%. Thus in Ernakulam, the juice and the quid were mostly spat out, whereas in Pune they were swallowed. The regional variations in the characteristics of submucous fibrosis could be related to the differences in the areca nut chewing habit between the two areas.

An oral lichen planus-like lesion in Indian betel-tobacco chewers.

During an epidemiologic study of oral cancer and precancerous lesions among Indian villagers, a lichen planus-like lesion was observed in Kerala. The lesion consisted of white, wavy, parallel, non-elevated lines that could not be scraped off. The lesion occurred exclusively among chewers and at the site of placement of quid. There were no subjective symptoms. The peak prevalence of the 35 diagnosed lesions was in the 35-44 years age-group for males and 45-54 for females. There was a marked female predominance. The histologic features were very similar to those seen in oral lichen planus.

Incidence of oral leucoplakias among 20,358 Indian villagers in a 7-year period.

A group of 20,358 villagers in two districts of India has been followed for 7 years to study the incidence of oral leucoplakia. The follow-up rate of the population in two districts ranged from 61% to 71%. In one of the districts (Bhavnagar) no new cases of leucoplakia were found among females in the 7-year period. Among males 105 cases developed (4-0/1000/year). The incidence was highest among hookli (clay pipe) smokers. In the Ernakulam district the incidence among males was 3-3/1000/year whereas among females it was 1-9/1000/year. The mixed habits group had the highest incidence of oral leucoplakias (7-2 and 9-9/1000/year among males and females respectively).