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.