For the Journal of the Indian Medical Association Mouth Cancer in India A New Epidemic? Prakash C. Gupta Epidemiology Research Unit, Tata Institute of Fundamental Research, Mumbai Correspondence to Dr. Prakash C. Gupta Epidemiology Research Unit Tata Institute of Fundamental Research Homi Bhabha Road, Colaba Mumbai 400 005 Tel. 022 215 2971 x 2553 Fax. 022 215 2110 E-mail pcgupta@tifr.res.in
ABSTRACT Oral cancer has been traditionally described as a major form of cancer in India although on the basis of cancer registry data, it was thought that the incidence has decreased. There are several recent reports in the literature however, predicting an increase in mouth cancer incidence in India. This prediction is based upon observation of an increasing prevalence of oral submucous fibrosis, especially in younger individuals, caused by gutka, an industrially manufactured food item. A comparison of the age distribution of recently reported oral submucous fibrosis cases and incident cases reported in the past clearly establishes that the disease is now occurring at much younger ages. A comparison of the age specific incidence rates of mouth cancer (ICD 143-5) during 1983-87 and 1995 in the city of Ahemdabad shows that the incidence has significantly increased in the younger population (< 50 yr). Since tongue cancer (ICD 141) does not show a similar increase, it is concluded that the increase in mouth cancer incidence is real. Urgent public health measures are required to curb this new but avoidable epidemic.
INTRODUCTION It has been well recognized since the beginning of this century that oral cancer is one of the commonest cancers in India. For a long time this recognition was based upon hospital frequency statistics by looking at the proportion of oral cancer among all cancer cases diagnosed. The incidence data for the population based cancer registry first became available during 60s from Bombay and during 80s from several cities as a part of the National Cancer Registry Project of the Indian Council of Medical Research. The incidence data from these registries confirmed the fact that oral cancer was indeed a common form of cancer in India (1). The etiopathogenesis of oral cancer in India was investigated in many epidemiologic studies. It was established beyond any doubt that the habit of chewing of betel quid with tobacco, in addition to smoking, particularly bidi smoking, were main causative factors. The World Health Organization estimated that 90% of oral cancer among men in India could be attributed to the use of tobacco (2). The chewing of betel quid with tobacco necessitates frequent spitting of thick red juice. With increasing urbanization and education, this practice was becoming somewhat unacceptable. Looking at the trend of the incidence rate of oral cancer over the years, it was becoming apparent that oral cancer was decreasing in the country (3). In recent years, situation again seems to have changed. There is a widespread impression among practicing physicians, especially dentists and ENT surgeons, that the incidence of oral submucous fibrosis in the population has increased manifold especially among younger generation. This has lead to an apprehension that within near future, the incidence of mouth cancer would show an increase (4). Oral submucous fibrosis is a chronic debilitating disease of the mouth in which fibrous bands develop, mucosa loses its elasticity and mouth opening gets restricted. In extreme cases, the mouth opening may be enough just for a straw to pass through. This disease does not regress and it has no well accepted line of management. The most serious aspect of this disease is its precancerous nature confirmed through several types of evidences. Most persuasive one is perhaps from a cohort study where the relative risk of malignant transformation of oral submucous fibrosis compared to individuals without any precancerous lesion was established as 397.3 after controlling for the use of tobacco (5). At first oral submucous fibrosis was an enigmatic disease. Several etiological hypothesis were proposed to explain a rather unique epidemiologic pattern of its occurrence. Only one hypothesis has withstood all kinds of tests and is now almost universally accepted: chewing of areca nut in any form is a causative factor for oral submucous fibrosis. This association has been confirmed in a comprehensive review of evidence (6) and reconfirmed in recent studies (7).
The reason for this sudden increase in the incidence of oral submucous fibrosis in the country has been well delineated. A commercial product containg areca nut (generic name - pan masala) and most often tobacco (generic name gutka) has been heavily advertised, intensively promoted and widely marketed all over the country. As a result the habit of gutka chewing has been picked up by the younger generation and the industry has increased from nothing to billions of rupees within 2 to 3 decades. In this paper, two issues are examined with the help of available data: 1) whether the disease is now really occurring at a younger age; and, 2) as per the prediction, whether there has been any increase in the incidence of oral cancer? METHODS Published data indicating age distribution of prevalent oral submucous fibrosis cases are available (4, 8). Comparing these data with earlier reports on age distribution of oral submucous fibrosis cases clearly demonstrates lower age distribution for current reports. On comparing age distribution of two prevalent series for a chronic lifelong condition, a doubt lingers: whether the cases are really occurring at an early age or they are simply getting detected earlier? To address this doubt, age distribution of recent prevalent cases is compared with age distribution of incident cases available from a 10-year follow-up study of 30 000 individuals in three districts of India (9). Since the follow-up with mouth examination was annual, the age distribution of incident cases was almost the same as the age distribution of the development of the disease. Oral submucous fibrosis arising out of gutka use most often involves buccal mucosa and by extension gums, floor of the mouth, soft palate and uvula but less often tongue. Ahemdabad is a city where the use of gutka and similar preparations like mawa, has become very popular and it has population-based cancer registry providing incidence rates for many years. Recently the annual report of the registry for the year 1995 has been released (10) and earlier incidence rates for the period 1983-87 are available from the Cancer Incidence in Five Continents vol. VI (11). For these two time-periods, the age-specific incidence rates were compared for mouth cancer by combing the three sites ICD 143, 144 and 145 and for the tongue (ICD 141). RESULTS Table 1 provides age distribution of oral submucous fibrosis cases from two recent studies and compares it with the age distribution of incident cases. In two recent studies, 85% (138 out of 164) and 70% (out of 200) prevalent cases were less than 35 years. Compared to this, in the older 10 year follow-up study of 30 000 individuals in three districts of India, just 4% (1 out of 26) incident cases were less than 35 years. The difference was highly significant.
Figure 1 shows the age distribution of mouth cancer (ICD 143-5) for the two time periods 1995 and 1983-87. Due to small number of cases, the 1995 data was quite wobbly in 5 year age-groups and therefor the incidence rates were re-computed for 10 year age intervals. For higher age groups (60 and over) the incidence rate has clearly decreased. This is in consonance with observation that the trend in the incidence of oral cancer in India is towards the decrease. At lower ages (< 50 years) however, the incidence appears to have increased substantially. Figure 3 provides similar curves for tongue cancer (ICD 141). Here there is no ambiguity. For the entire age range, there is a clear cut decrease in the incidence. Table 2 shows the age distribution of the observed cases of cancers of the mouth (ICD 143-5) and the tongue (ICD 141) in the year 1995. It also shows the expected number of cases of these two cancers calculated on the basis of the denominator in 1995 and incidence rates during 1983-87. The differences are quite apparent up to age 49, observed cases of mouth cancer were 48 whereas expected were 31.8, the difference being highly significant (p <.01). In contrast, for tongue cancer, up to 49 years age, 35 cases were observed whereas 47.3 were expected. DISCUSSION The recent predictions of an increase in the incidence of mouth cancer in India are contrary to the available data from cancer registries showing a decreasing trend in mouth cancer so far. Since this prediction of the increase in incidence of oral cancer has serious public health implications, the evidence needs to be examined rather carefully. The most persuasive part of the evidence perhaps is the decreasing age distribution of oral submucous fibrosis cases. Given the chronic, non-treatable nature of this disease and high relative risk of malignant transformation, a decreasing age distribution would demonstrate a clear possibility of increasing incidence of oral cancer. The age distribution of incidence cases must correspond to the age distribution of the development of oral submcous fibrosis since all these individuals were normal in baseline and subsequent examinations until they were diagnosed with oral submucous fibrosis. Moreover these incidence cases are from a large database, 10 year follow-up of 30 000 individuals in three areas of India. The data in Table 2 thus confirm that within less than two decades, the age distribution of oral submucous fibrosis has changed quite drastically. If this prediction is based on such strong evidence, are there any tell-tale signs yet of increasing incidence of oral cancer? Figure 1 clearly establishes that whereas for the older cohort, the incidence of mouth cancer is decreasing in consonance with the reported observations so far; for the younger cohort, the incidence of mouth cancer is already showing an increase, in consonance with the reported prediction. The observed number of cases in the younger individuals (<50 years) are 25% greater than expected, calculated on the basis of 1983-87 incidence rates. This difference is highly significant (p < 0.01).
An increase in the incidence rate of mouth cancer over time, even though significant, may not be immediately regarded as real and conclusions drawn on that basis. The possibility that it could be an artifact ought to be carefully examined. The rates could be different due to artificial differences in numerator or in the denominator. The numerators could be artificially different theoretically because of differences in ascertainment, for example, better and easier availability of diagnostic procedures, a better coverage by the cancer registry through abstraction of data from many more clinicians and hospitals, or improved record keeping by collaborating hospitals. The denominator could be different due to larger in-migration of population within the city limits. Such an increase would be difficult to account for while estimating the city population for the desired year through statistical modeling procedures. Such a phenomenon would artificially inflate the incidence rates. To take care of these possibilities, similar analyses were performed for tongue cancer. Mouth and tongue cancers are similar in terms of ease of diagnosis, diagnostic requirements and even overall incidence. Thus whatever reason could artificially alter numerator or denominator for mouth cancer, it would also affect the incidence of tongue cancer in a similar way. The major difference was that gutka use and consequent oral submucous fibrosis seem to involve the buccal mucosa much more than the tongue. The fact that the differences in the incidence of mouth (ICD 143-5) and tongue cancer (ICD 145) were in opposite direction demonstrates that they were not artifacts. The fact that the incidence of mouth cancer was significantly higher in younger population after a gap of just a decade compels us to seriously consider possible external reasons for such an increase. Since one specific reason for such an increase, namely widespread promotion of an industrially manufactured product, gutka, has already been postulated on the basis of strong evidence, and no other specific reason is in sight, the conclusion seems inescapable. It has been established on the basis of a comprehensive review that gutka is carcinogenic (12). The predicted epidemic of oral cancer, almost completely attributable to gutka, thus seems to have already begun. This is most unfortunate and ironical because gutka satisfies all criteria of being a food item. Immediate public health action is needed to control this new epidemic that is completely avoidable. REFERENCES 1. National Cancer Registry Programme (1992). Biennial Report (1988-89) of the National Cancer Registry Programme. New Delhi. Indian Council of Medical Research. 2. World Health Organization (1984). Control of oral cancer in developing countries. Report of a WHO meeting. Bulletin World Health Organization, 62: 817-830.
3. Jayant K, Yeole BB (1987) Cancers of the upper alimentary and respiratory tracts in Bombay, India: a study of incidence over two decades. Br J Cancer 56(6):847-52 4. Gupta PC, Sinor PN, Bhonsle RB et al (1998). Oral submucous fibrosis in India: A new epidemic? Natl Med J India; 11(3): 113-116. 5. Gupta PC, Bhonsle RB, Murti PR, Daftary DK, Mehta FS, Pindborg JJ (1989) An epidemiologic assessment of cancer risk in oral precancerous lesions in India with special reference to nodular leukoplakia. Cancer 63: 2247-2251. 6. Murti PR, Bhonsle RB, Gupta PC, Daftary DK, Pindborg JJ, Mehta FS (1995) Etiology of oral submucous fibrosis: role of areca nut chewing. J Oral Pathol Med 24:145-152. 7. Shah N, Sharma PP (1998) Role of chewing and smoking habits in the etiology of oral submucous fibrosis (OSF): a case-control study. J Oral Pathol Med 27(10):475-9 8. Hazare VK, Goel RR, Gupta PC (1998) Oral submucous fibrosis, areca nut and pan masala use: A case-control study. Natl Med J India. 11(6): 299. 9. Gupta PC, Mehta FS, Daftary DK, et al (1980) Incidence of oral cancer and natural history of oral precancerous lesions in a 10-year follow-up study of Indian villagers. Community Dent Oral Epidemiol 8: 287-333. 10. Population Based Cancer Registry Ahemdabad Urban Agglomeration Area, 1995 Annual Report. The Gujarat Cancer and Research Institute. 1999. Ahemdabad. 11. Parkin DM, Muir CS, Whelan SL, Gao YT, Ferley J, Powell J. Cancer Incidence in Five Continents Volume VI. IARC Scientific Publications No. 120. Lyon. 1992. International Agency for Research on Cancer. 12. Chaudhry K (1999) Is pan masala-containing tobacco carcinogenic? Natl Med J India 12(1):21-27.
Legends Figure 1. A comparison of the age- specific incidence rates of mouth cancer (ICD 143-5) during 1995 and 1983-87 in the city of Ahemdabad Figure 2. A comparison of the age- specific incidence rates of tongue cancer (ICD 141) during 1995 and 1983-87 in the city of Ahemdabad
Table 1. A comparison of the age distribution of recently reported oral submucous fibrosis cases and incident cases reported in the past. Age Gupta et al. 1998 Hazarey et al. 1998 Gupta et al. 1980 15-34 138 > 140 1 35-54 25 < 60 19 55 and over 1 6 Total 164 200 26
Table 2 Age distribution of observed number of cancers in 1995 compared with expected number calculated on the basis of the incidence rates during 1983-87 Mouth (ICD 143-5) Tongue (ICD 141) Observed Expected Observed Expected 10-14 0 0.4 1 0.0 15-19 0 0.0 0 0.4 20-24 0 1.2 1 1.6 25-29 0 1.5 1 2.2 30-34 7 2.6 2 3.3 35-39 7 5.6 5 7.3 40-44 16 9.4 11 11.0 45-49 18 11.1 14 21.5 50-54 11 12.9 20 27.7 55-59 15 11.2 18 22.7 60-64 11 11.4 7 28.2 65-69 8 7.6 13 18.6 70-74 2 6 9 16.0 75-79 1 2.9 4 5.5 80+ 1 1.6 5 4.9
Figure 1. Figure 2