Babu Mathew

Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial

BACKGROUND Oral cancer is common in men from developing countries, and is increased by tobacco and alcohol use. We aimed to assess the effect of visual screening on oral cancer mortality in a cluster-randomised controlled trial in India. METHODS Of the 13 clusters chosen for the study, seven were randomised to three rounds of oral visual inspection by trained health workers at 3-year intervals and six to a control group during 1996-2004, in Trivandrum district, Kerala, India. Healthy participants aged 35 years and older were eligible for the study. Screen-positive people were referred for clinical examination by doctors, biopsy, and treatment. Outcome measures were survival, case fatality, and oral cancer mortality. Oral cancer mortality in the study groups was analysed and compared by use of cluster analysis. Analysis was by intention to treat. FINDINGS Of the 96,517 eligible participants in the intervention group, 87,655 (91%) were screened at least once, 53,312 (55%) twice, and 29,102 (30%) three times. Of the 5145 individuals who screened positive, 3218 (63%) complied with referral. 95,356 eligible participants in the control group received standard care. 205 oral cancer cases and 77 oral cancer deaths were recorded in the intervention group compared with 158 cases and 87 deaths in the control group (mortality rate ratio 0.79 [95% CI 0.51-1.22]). 70 oral cancer deaths took place in users of tobacco or alcohol, or both, in the intervention group, compared with 85 in controls (0.66 [0.45-0.95]). The mortality rate ratio was 0.57 (0.35-0.93) in male tobacco or alcohol users and 0.78 (0.43-1.42) in female users. INTERPRETATION : Oral visual screening can reduce mortality in high-risk individuals and has the potential of preventing at least 37,000 oral cancer deaths worldwide.

Response of oral leukoplakias to the administration of vitamin A

Tobacco/betel nut chewers (Kerala, India) with well-developed oral leukoplakias were chosen for a short-term intervention trial of vitamin A therapy. Participants were randomly distributed into two groups, one receiving 200,000 IU vitamin A per week (0.14 mg/kg body wt/per day) for 6 months, and the other receiving placebo capsules. Their cancer-causing habit, which can be quantitated (an average of 13.1 betel quids/day, 26.1 min/quid), did not change during the trial period. The 6-month oral administration of vitamin A caused complete remission in 57.1% of participants, and a total suppression of the development of new leukoplakias in all chewers receiving vitamin A (n = 21), as compared to 3% and 21%, respectively, in the placebo group (n = 33). The results were substantiated by examining the histological and cytological changes on small biopsies which were taken at the onset and at the completion of the trial period. Over the 6-month period of vitamin A administration, the number of layers of spinous cells decreased in 85% of the participants, the loss of polarity of basal cells was reduced from 72.2% to 22.2% of chewers, subepidermal lymphocytic infiltration was greatly diminished from 66.7% to 5.5% of chewers, and nuclei with condensed chromatin disappeared from the epidermal layer (72.2% before to 0% at the end of the trial).

Evaluation of chemoprevention of oral cancer with spirulina fusiformis

The blue-green microalgae Spirulina, used in daily diets of natives in Africa and America, have been found to be a rich natural source of proteins, carotenoids, and other micronutrients. Experimental studies in animal models have demonstrated an inhibitory effect of Spirulina algae on oral carcinogenesis. Studies among preschool children in India have demonstrated Spirulina fusiformis (SF) to be an effective source of dietary vitamin A. We evaluated the chemopreventive activity of SF (1 g/day for 12 mos) in reversing oral leukoplakia in pan tobacco chewers in Kerala, India. Complete regression of lesions was observed in 20 of 44 (45%) evaluable subjects supplemented with SF, as opposed to 3 of 43 (7%) in the placebo arm (p < 0.0001). When stratified by type of leukoplakia, the response was more pronounced in homogeneous lesions: complete regression was seen in 16 of 28 (57%) subjects with homogeneous leukoplakia, 2 of 8 with erythroplakia, 2 of 4 with verrucous leukoplakia, and 0 of 4 with ulcerated and nodular lesions. Within one year of discontinuing supplements, 9 of 20 (45%) complete responders with SF developed recurrent lesions. Supplementation with SF did not result in increased serum concentration of retinol or beta-carotene, nor was it associated with toxicity. This is the first human study evaluating the chemopreventive potential of SF. More studies in different settings and different populations are needed for further evaluation.

Chemoprevention of oral leukoplakia with vitamin A and beta carotene: an assessment.

We conducted a double-blind placebo-controlled trial to evaluate the chemopreventive potential of either vitamin A alone or beta carotene alone in subjects with oral leukoplakia in Kerala, India. We randomised 160 fishermen and women with oral precancerous lesions to receive oral vitamin A (retinyl acetate 300,000 IU/week x 12 months, n = 50), or beta carotene (360 mg/week x 12 months, n = 55), or placebo (n = 55). Blood, saliva and urine samples were collected at baseline and at exit to study serum micronutrients and mutagenicity assays. Biopsies of the mucosal lesions at entry were performed for histopathological exclusion of malignancy. The subjects were examined once every 2 months to establish clinical response of lesions and toxicity, if any. The results are based on 43 complaint subjects on placebo, 42 on vitamin A and 46 on beta carotene. The complete regression rates were: 10% in the placebo arm, 52% with vitamin A and 33% with beta carotene (P < 0.0001). Homogeneous leukoplakias and smaller lesions responded better than non-homogeneous and larger lesions. No major toxicities were observed. Half of the responders with beta carotene and two thirds with vitamin A relapsed after stopping supplementation. Serum beta carotene concentration increased substantially with beta carotene administration while with vitamin A supplementation there was no change in serum retinol levels. In the vitamin A treated group there was a significant decrease in serum alpha tocopherol. Vitamin A administration resulted in a significant remission of oral leukoplakia without any side effects of prolonged vitamin A supplementation. The results of this study, as well as those from previous studies, appear to provide strong supporting evidence to justify long term trials with vitamin A in subjects with high-risk leukoplakias with oral cancer as an endpoint.

Early findings from a community-based, cluster-randomized, controlled oral cancer screening trial in Kerala, India

Oral cancer satisfies the criteria for a suitable disease for screening, and oral visual inspection is a suitable test for oral cancer screening. The efficacy of screening in reducing mortality from oral cancer has not yet been evaluated. The authors describe a cluster‐randomized, controlled oral cancer screening trial in southern India and its early results.

Cost-effectiveness of oral cancer screening: results from a cluster randomized controlled trial in India

OBJECTIVE To evaluate oral cancer screening by visual inspection. METHODS A cluster randomized controlled trial was initiated in Trivandrum district, Kerala, India. Of 13 population clusters, seven were randomly allocated to three rounds of screening between 1996 and 2004, while standard care was provided in six (control arm). An activity-based approach was employed to calculate costs associated with various components of the screening trial. Information on the resources used and on clinical events in each trial arm was derived from trial databases. Total costs for each cluster were estimated in 2004 United States dollars (US

Risk factors for multiple oral premalignant lesions

). The incremental cost per life-year saved was calculated for all eligible individuals and for high-risk individuals (i.e. tobacco or alcohol users). FINDINGS The proportion of oral cancers detected at an early stage (i.e. stage I or II) was higher in the intervention arm than the control arm (42% versus 24%, respectively). The incremental cost per life-year saved was US

Long term effect of visual screening on oral cancer incidence and mortality in a randomized trial in Kerala, India

835 for all individuals eligible for screening and US

Socioeconomic status, lifestyle factors and oral premalignant lesions.

156 for high-risk individuals. Oral cancer screening by visual inspection was performed for under US

Alcohol drinking, body mass index and the risk of oral leukoplakia in an Indian population

6 per person. CONCLUSION The most cost-effective approach to oral cancer screening by visual inspection is to offer it to the high-risk population. Targeted screening of this group will ensure that screening can be offered at a reasonable cost in a limited-resource setting.