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Oral cancer in india continues in epidemic proportions  evidence base and policy initiativesi dj131
Oral cancer in india continues in epidemic proportions  evidence base and policy initiativesi dj131
Oral cancer in india continues in epidemic proportions  evidence base and policy initiativesi dj131
Oral cancer in india continues in epidemic proportions  evidence base and policy initiativesi dj131
Oral cancer in india continues in epidemic proportions  evidence base and policy initiativesi dj131
Oral cancer in india continues in epidemic proportions  evidence base and policy initiativesi dj131
Oral cancer in india continues in epidemic proportions  evidence base and policy initiativesi dj131
Oral cancer in india continues in epidemic proportions  evidence base and policy initiativesi dj131
Oral cancer in india continues in epidemic proportions  evidence base and policy initiativesi dj131
Oral cancer in india continues in epidemic proportions  evidence base and policy initiativesi dj131
Oral cancer in india continues in epidemic proportions  evidence base and policy initiativesi dj131
Oral cancer in india continues in epidemic proportions  evidence base and policy initiativesi dj131
Oral cancer in india continues in epidemic proportions  evidence base and policy initiativesi dj131
Oral cancer in india continues in epidemic proportions  evidence base and policy initiativesi dj131
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Oral cancer in india continues in epidemic proportions evidence base and policy initiativesi dj131

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  • 1. International Dental Journal 2013; 63: 12–25 REVIEW ARTICLE doi: 10.1111/j.1875-595x.2012.00131.xOral cancer in India continues in epidemic proportions:evidence base and policy initiativesBhawna Gupta1, Anura Ariyawardana2,3 and Newell W. Johnson21 Epidemiologist, Global Disease Detection Centre India, National Centre for Disease Control, New Delhi, India; 2Population Oral HealthGroup, Population and Social Health Research Programme, Griffith Health Institute, Griffith University, Queensland, Australia; 3School ofDentistry, James Cook University, Queensland, Australia.Objectives: India has the highest number of cases of oral cancer in the world and this is increasing. This burden is notfully appreciated even within India, despite the high incidence and poor survival associated with this disease. Because theaetiology of oral cancer is predominantly tobacco-related, the immense public health challenge can be melioratedthrough habit intervention. Methods: We reviewed current rates of incidence, mortality and survival, and investigatedthe determinants of disease and current prevention strategies. Results: In addition to tobacco smoking and the myriadother forms of tobacco use prevalent in India, risk factors include areca nut consumption, alcohol consumption, humanpapillomavirus, increasing age, male gender and socioeconomic factors. Although India has world-leading cancer treat-ment centres, access to these is limited. Further, the focus of health care services remains clinical and is either curative orpalliative. Conclusions: Although the efforts of agencies such as the Ministry of Health and Family Welfare and theIndian Dental Association are laudable, enhanced strategies should be based on common risk factors, focusing on pri-mary prevention, health education, early detection and the earliest possible therapeutic intervention. A multi-agencyapproach is required.Key words: Oral cancer, epidemiology, risk factors, prevention, policy, tobacco, alcohol, diet, HPVThe Indian subcontinent, especially India itself because Collectively, these conditions represent the sixth mostof its large population, has long been regarded as the common type of cancer in the world. Annual estimatedglobal epicentre of oral cancer. The malady recognised global incidences amount to around 275,000 cases ofby the world as oral cancer was first described in the oral and 130,300 cases of pharyngeal cancers excludingSushruta Samhita, a treatise on Indian surgery written cancers of the nasopharynx, two thirds of which occurin Sanskrit around 600 BC1. The World Health Orga- in developing countries5. In this paper, we define oralnization (WHO) regards oral cancer as a major public cancer as any malignant neoplasm occurring on the lipshealth challenge in India2. The burden it imposes, in or within the mouth/oral cavity, including on the ton-terms of incidence, mortality, survival and the determi- gue (ICD-10 codes: C00–C06)6. Wherever possible, wenants of disease, as well as the inevitable stretching of have excluded diseases of the major salivary glandslimited health care resources, is not fully appreciated, (C07, C08) and nasopharynx (C11) because of their dif-particularly in India. There is wide variation in the glo- ferent biology4. Diseases of the oropharynx (C10), pyri-bal burden of this disease, with incidences in India and form sinus (C12) and hypopharynx (C13) have someacross South and Southeast Asia amongst the highest in commonality in risk factors and behaviour and there-the world3. Incidence is also increasing elsewhere, such fore data for disease in these sites are given where rele-as in parts of Western and Eastern Europe, Latin Amer- vant. Because of inconsistencies in the groupings usedica and the Pacific regions3. by different authors and databases, we have striven to Malignant neoplasms of the lip, oral cavity and oro- list the sites included whenever data are given.pharynx [International Classification of Diseases (ICD)- Today, 90–95% of all new cases of oral malignancy10 codes: C00–C14], excluding other pharyngeal sites in most populations, including that in India, are squa-(C11–C13), are often grouped together4. They have mous cell carcinomas (SCC) arising from liningcommon risk factors and, to some extent, behaviours. mucosa7. Squamous cell carcinomas of the oro- and12 © 2012 FDI World Dental Federation
  • 2. The epidemic of oral cancer in Indiahypopharynx are increasing in many countries, partic- IARC Screening Group (http://screening.iarc.fr/atlas-ularly in the West. Many cases are related to the tra- oral.php?lang-1). We also reviewed the textbooks Headditional risk factors of smoking and heavy alcohol and Neck Cancer: Multimodality Management (Bernierconsumption, and others to infection with human J, ed., Springer/Humana Press, 2011) and Oral Cancerpapillomavirus (HPV). However, in the Indian con- (Shah JP, Johnson NW, Batsakis JG, eds., Martintext, oral cancer itself is most common, and its aetiol- Dunitz, 2003).ogy is dominated by tobacco use, especially ofsmokeless tobacco, areca [betel] nut consumption and RESULTSalcohol abuse, all of which frequently act in the pres-ence of poor diet and poor dental health. This is a Descriptive epidemiologypreventable disease: this paper focuses on the publichealth challenge presented by oral cancer in India. Global burden of oral cancer Estimated incidence, mortality and 5-year prevalencesMATERIALS AND METHODS of lip and oral cavity cancer, as estimated by GLOBOCAN 2008, for the whole world and forSearch strategy India, are summarised in Table 1. Two thirds of theOur extensive literature review screened the PubMed, global burden of these cancers occurs in developingEMBASE, CINAHL (Cumulative Index to Nursing and countries and the Indian subcontinent accounts forAllied Health Literature), Cochrane Library and Coch- nearly one third of global incidence8.rane Oral Health Group’s Trials Register databases up Although the incidence rates given for oral cancerto October 2011 for literature published in English for all ages (0–75 years) are lower in India [weightedonly, irrespective of publication date. Main search age-standardised rate (ASR-w) for both sexes com-terms were: ‘oral cancer’; ‘mouth cancer’; ‘risk factors’; bined: 7.5 per 100,000 per annum] than in some‘policy’; ‘interventions’ and ‘treatment’, with ‘India’. other developing countries, notably Melanesia (ASR-Supplementary key words were: ‘tobacco’; ‘alcohol’; w 17.8), Maldives, Taiwan, Brunei and Sri Lanka,‘betel nut’; ‘areca nut chewing’; ‘socioeconomic deter- India contributes the highest number of new casesminants’; ‘oral cancer epidemiology’; ‘oral cancer pre- because of its huge population. Over five people dievention’, and ‘oral cancer treatment’. A total of 793 from oral cancer every hour every day in India andarticles were retrieved, for which the titles and abstracts almost the same number die from cancer of the oro-were evaluated. This resulted in the retention of 131 pharynx and hypopharynx3.articles which were read in full; 32 of these wereexcluded for not reporting relevant outcomes. Burden of oral cancer in India The ‘related articles’ links and the references of thearticles reviewed were hand-searched for additional Oral cancer (ICD-10 codes: C01–C06) ranks amongstreferences. This resulted in the identification of a fur- the three most common cancers in India and in somether 140 papers. areas accounts for almost 40% of total cancer Papers excluded were those in which some confusion deaths9. Figure 2 shows estimated incidences andover the anatomical sites of origin of the malignancies mortality in men and women of all ages in India.described was apparent, papers in which the numbers Approximately 70,000 new cases and more thanof cases were small and the data were judged to be not 48,000 oral cancer-related deaths occur yearly10. Ingeneralisable, and papers reporting studies in which the most regions of India, oral cancer is the second mostanalytical methods were judged to be faulty. A total of common malignancy diagnosed in men, accounting99 papers were fully evaluated. The most relevant data for up to 20% of cancers, and the fourth most com-were found in official publications of the Indian Coun- mon in women (Figure 3)3,11.cil of Medical Research (ICMR), derived from the indi- Note, however, that GLOBOCAN data for India asvidual registries maintained across the nation a whole are extrapolations based on the estimated(Figure 1). We reviewed the following databases and population of the nation and data from regional can-websites: GLOBOCAN 2008; National Centre for Dis- cer registries. As will become evident in this text,ease Informatics and Research (http://www.ncdirindia. there is considerable variation among registries in theorg/); National Cancer Registry Programme (http:// cases recorded. Further, as cancer registration is notwww.icmr.nic.in/ncrp/cancer_reg.htm); International compulsory in India, it is probable that the true inci-Agency for Research on Cancer (IARC) (http://www. dence and mortality are much higher: many cases goiarc.fr/); International Head and Neck Epidemiology unrecorded and/or are lost to follow-up12.(http://inhance.iarc.fr/index.php); Centers for Disease Over 100,000 cases of oral cancer are cur-Control and Prevention (http://www.cdc.gov), and the rently recorded on cancer registers across India3.© 2012 FDI World Dental Federation 13
  • 3. Gupta et al. Figure 1. Locations of cancer registries in India.Table 1 Incidence, mortality and 5-year prevalence rates for cancer of the lip and oral cavity (ICD-10 codes:C00–C08) in both sexes in 2008Population World More developed regions Less developed regions South Central Asia IndiaIncidence Cases, n* 263,020 91,148 171,872 97,623 69,820 ASR-w, %† 3.8 4.4 3.6 7.4 7.5 Cumulative risk, %‡ 0.44 0.51 0.42 0.88 0.89Mortality Cases, n* 127,654 30,689 96,965 63,610 47,653 ASR-w, %† 1.8 1.4 2.0 4.9 5.2 Cumulative risk, %‡ 0.22 0.16 0.24 0.59 0.615-year prevalence 610,656 258,973 351,683 172,534 107,690*Crude rates are expressed as the annual rate per 100,000 persons at risk.† Weighted age-standardised rates (ASR-w) are expressed as rates per 100,000 population.‡ Cumulative risk for age (0–74 years), %.Data are derived from GLOBOCAN 2008 (http://globocan.iarc.fr/).14 © 2012 FDI World Dental Federation
  • 4. The epidemic of oral cancer in India 35 32.3 Age-standardised rate (weighted) per 100,000 population 30 29.2 25 24.5 20 Incidence 16.5 16.5 15.3 Mortality 15 14.6 11.4 11 11 10.8 10.2 9.9 9.8 9.8 9.6 10 9.5 9.4 9.3 9.2 6.9 6.8 7.3 7 6.8 6.6 5.6 5.2 5.9 5.2 5 3.8 3.6 4.1 4.2 2.5 3.3 1.2 1.5 1.5 1.4 (a) 0 18 16 Age-standardised rate (weighted) per 100,000 population 16 14 12.9 12 9.9 10 Incidence 8.6 Mortality 8.1 8.2 8 7 6.2 6 5.8 5.2 5.2 5.1 5 4.5 4.8 4.5 4.1 4.1 3.9 3.7 3.7 3.6 3.6 3.5 4 3.6 3.4 3.2 3 2.7 2.3 2.4 2.4 2.5 1.8 2 1.2 1.1 1.5 1.2 0.6 0.6 (b) 0 Figure 2. (a) Incidence and mortality rates of cancers of the lip and oral cavity (ICD-10 codes: C00–C08) among males of all ages in the 20 countrieswith the highest rates in 2008. India ranks 14th in incidence, fourth for mortality and approximately equal first with its neighbours, Nepal and Bangladesh, for poor death : registration ratio. Source: GLOBOCAN 2008 (http://globocan.iarc.fr/bar_site.asp?selection=12010&title=Lip%2C+oral+cavity& sex=1&statistic=2&populations=5&window=1&grid=1&info=1&orientation=1&color1=4&color1e=&color2=5&color2e=&submit=%A0Execute%A0). (b) Incidence and mortality rates of cancers of the lip and oral cavity (ICD-10 codes: C00–C08) among females of all ages in the 20 countries with the highest rates in 2008. India ranks eighth in incidence and fifth for mortality. Source: GLOBOCAN 2008 (http://globocan.iarc.fr/bar_site.asp? selection=12010&title=Lip%2C±oral±cavity&sex=2&statistic=2&populations=5&window=1&grid=1&info=1&orientation= 1&color1=4&color1e=&color2=5&color2e=&submit=%A0Execute%A0).The overall incidence derived from Indian databases on the AAR of tongue cancer amongst females aremay be as high as 19 per 100,000 per annum3,13. very scarce.According to the National Cancer Registry Pro-gramme (NCRP), Bhopal district has the highest age-adjusted incidence rate (AAR) in the world for cancers Projected burden of oral cancer in India by 2020.of both the tongue (ICD-10 codes: C01, C02) (10.9 Numbers of oral cancer cases (IDC-10 codes: C00–per 100,000) and mouth (ICD-10 codes: C03–C06) C08) and deaths in India predicted by the ICMR(9.6 per 100,000) among males (Figure 4). Among by the year 2020 are presented in Figure 515. Thisfemales, Bhopal has the second highest AAR (7.2 per substantial rise places a severe burden on the100,000) for cancer of the mouth (Figure 4)14. Data nation. The cumulative lifetime risk for mortality© 2012 FDI World Dental Federation 15
  • 5. Gupta et al. Lung 10.9 9.8 Lip, oral cavity 9.8 6.8 Other pharynx 8.3 7.2 Oesophagus 6.5 6 Stomach 4.7 4.6 Larynx 4.6 3 Colorectum 4.3 3.2 Incidence Prostate 3.7 2.5 Mortality Leukaemia 3.5 2.9 Liver 3.2 3 Non-Hodgkin 3 lymphoma 2.1 2.8 Bladder 1.6 Brain, nervous 2.5 2.1 system (a) 0 5 10 15 Age-standardised rate (weighted) per 100,000 population Cervix uteri 27 15.2 Breast 22.9 11.1 Ovary 5.7 4.1 Lip, oral cavity 5.2 3.6 Oesophagus 4.2 3.6 2.9 Stomach 2.7 3.5 Colorectum 2.5 2.5 Lung Incidence 2.3 2.6 Leukaemia Mortality 2.1 1.8 Other pharynx 1.5 2.4 Gallbladder 1.4 Brain, nervous system 1.7 1.4 (b) 0 5 10 15 20 25 30 Age-standardised rate (weighted) per 100,000 population Figure 3. Most frequent cancers among (a) males and (b) females in India according to GLOBOCAN data for 2008. ‘Lip, oral cavity’ data refer to ICD-10 codes C00–C08. ‘Other pharynx’ data refer to ICD-10 codes: C09, C10 and C12–C14. Source: Ferlay et al.3 [Note: these authors explain: ‘As no national data are available, GLOBOCAN first estimated the urban and rural populations by sex and age in 2008 by applying the urban : rural ratio in 2008 (3 : 7) to the estimated total population of India in 2008, and partitioning this by sex- and age-proportions from the 2001 census. National cancer mortality was estimated using 5-year relative survival by site (all ages) in rural and urban Indian cancer registries) applied to the estimated 2008 rural and urban inci- dence. The number of cancer deaths (all ages) was partitioned by age using proportions from Mumbai and Chennai (1998–2002) cancer mortality data’].from lip or oral cavity cancer in India for males world, mean overall 5-year survival rates in oraland females aged 0–74 years is 61%3. cancer are still hovering around 50% and rates in India are estimated to be 40–45%17. Metastasis to regional lymph nodes is the single most importantSurvival. Survival for each cancer site (all clinical prognostic factor in predicting local and distantstages included) is described in terms of 5-year age- failure, as well as survival. Significantly, 10–30% ofstandardised relative survival16. In most parts of the patients with oral cancer subsequently develop16 © 2012 FDI World Dental Federation
  • 6. The epidemic of oral cancer in India India, Bhopal 10.9 India, Ahmedabad 9.3 France, Somme 7.6 India, Chennai 6 India, Delhi 6 India, Mumbai 5.4 USA, Hawaii: White 4.9 Puerto Rico 4.5 France, La Reunion 4.5 USA, Detroit, MI: Black 4.2 India, Bangalore 2.6 Singapore: Indian 2.6 New Zealand 1.6 India, Barshi 1.5 USA, Los Angeles, CA: 0.7 Chinese Italy, Ragusa Province 0.5 Costa Rica 0.5 The Gambia 0.2 China, Qi County: 0.1 Kaifeng, Shanxi (a) and Hebi 0 2 4 6 8 10 12 Rate per 100,000 India, Bhopal 9.6 France, Somme 9.3 Taiwan 9.3 France, La Reunion 8.6 USA, Connecticut 7.5 India, Mumbai 5.6 India, Chennai 5.6 Peurto Rico 4.8 India, Delhi 4.5 Singapore: Indian 3.6 Australia, Northern Territory 3.6 India, Bangalore 3.1 India, Barshi 2.7 USA, Hawaii: Chinese 1.3 Italy, Ragusa Province 0.6 Algeria, Algiers 0.4 USA, Los Angeles, CA: Filipino 0.3 Ecuador, Quito 0.3 Singapore, Malay 0.1 (b) 0 2 4 6 8 10 12 Rate per 100,000 Pakistan, South Karachi 9.3 India, Bhopal 7.2 India, Bangalore 6.7 India, Chennai 5.4 Singapore:Indian 5.1 India, Mumbai 4.4 Canada, Yukon 3.2 India, Delhi 2.3 USA, Hawaii: White 1.9 Switzerland, Geneva 1.8 India, Barshi 1.7 Uganda, Kyadondo 1.7 Cuba, Villa Clara 1.6 USA, Hawaii:Chinese 0.5 Uruguay, Montevideo 0.4 Italy, Mac. Province 0.2 Canada, Newfoundland 0.2 Mali, Bamako 0.1 China, Qi County: 0.2 Kaifeng, Shanxi (c) and Hebi 0 1 2 3 4 5 6 7 8 9 10 Rate per 100,000Figure 4. (a) Comparisons of age-adjusted incidence rates derived from population-based cancer registries (PBCRs) under the Indian National Cancer Registry Programme (INCRP) and international equivalents, for cancer of the tongue (ICD-10 codes: C01, C02) in males in 2001–2002. Globally, the highest rates areseen in Bhopal in central India and Ahmedabad in western India. Chennai, in the south, Delhi, in the north, and Mumbai, in the west, also show high rates. These data are the latest available. Source: http://www.ncrpindia.org/Cancer_Atlas_India/chapter6_Report.aspx?SiteName=Tong & ReportType= Int_Graph&Sex=M&MyBtn=View+Graph. (b) Comparisons of age-adjusted incidence rates derived from PBCRs under the INCRP and international equiva- lents, for cancer of the mouth (ICD-10 codes: C03–C06) in males in 2001–2002. Source: http://www.canceratlasindia.org/chapter6_Report.aspx?SiteName= Mout&ReportType=Int_Graph&Sex=M&MyBtn=View±Graph. (c) Comparisons of age-adjusted incidence rates derived from PBCRs under the INCRP and international equivalents, for cancer of the mouth (ICD-10 codes: C03–C06) in females in 2001–2002. Source: http://www.canceratlasindia.org/ chapter6_Report.aspx?SiteName=Mout&ReportType=Int_Graph&Sex=F&MyBtn=View+Graph.© 2012 FDI World Dental Federation 17
  • 7. Gupta et al.50,000 46,785 sis are as complex as for any other anatomical site. Males: Mouth Genetic predisposition plays a minor role expressed45,000 Males: Tongue through polymorphisms in carcinogen-metabolising Females: Mouth enzymes, the expression of oncogenes and oncosup-40,000 Females: Tongue pressor genes, and DNA repair genes23. There is35,000 increasing evidence of the importance of chronic30,000 28,584 inflammation, alterations in host immunity, metabo- lism and neo-angiogenesis, all of which may be trig-25,000 gered or enhanced by viruses, radiation, chemicals (notably from tobacco and alcoholic beverages), hor-20,000 17,741 mones, nutrients or physical irritants24.15,000 9,469 Oral potentially malignant disorders10,000 5,000 In South Asia, the majority of oral cancers arise from pre-existing longstanding lesions, now termed ‘oral 0 potentially malignant disorders’ (OPMDs)23 in recogni- 2008 2009 2010 2015 2020 tion of the fact that systemic, cellular and molecularFigure 5. Projected incidences of cancer of the mouth and tongue (ICD-10 changes are much wider than any particular macro- codes: C01–C06) in males and females in India in 2008, 2009, 2010, 2015 scopically visible oral lesion. In India, tobacco is the and 2020. Projections are derived from crude incidence rates generated by population-based cancer registries at Bangalore, Barshi, Bhopal, Chennai, major aetiological agent, producing visible lesions ofDelhi and Mumbai (for 2001–2005). By 2020, a sharp increase in the num- which so-called leukoplakia is the most common. Thisber of cases of mouth cancer in males is expected, with a slower increase in association has led to the aphorism ‘cancer is wherefemales. The burden of cancer of the tongue in both males and females will also rise by 2020. Source: Indian Council of Medical Research15. tobacco is’25. This knowledge explains the focus for the primary prevention of oral cancer on population-based strategies and on the early detection of OPMDs; habitsecond primary tumours of the aerodigestive intervention and follow-up are regarded as secondarytract18. prevention strategies conducted on an individual basis. Marked differences in survival have been noted amongrural (Barshi), semi-urban (Karunagappally) and smallurban (Bhopal) registries in India, whereas differences Major risk factors. Risk factors may vary for differentare small between the registries of the major cities of cultural and socioeconomic groups. However,Chennai and Mumbai, where more developed and acces- established risk factors for oral cancer in the Indiansible health care services are available16. Poor survival population include: tobacco in all its forms (smoked,rates can also be attributed to the fact that half of the oral chewed, used as oral snuff); the chewing of betel quidcancer cases in the nation are diagnosed at advanced (pan/paan); the heavy consumption of alcohol, andstages (stages III and IV) because patient’s delay in seek- the presence of an OPMD24,26. Other contributory oring medical care and acceptance of treatment is low5,19. predisposing factors include dietary deficiencies, Multiple treatment options are available in many particularly of vitamins A, C and E and iron, andcentres. These include surgery or radiotherapy alone, viral infections, particularly by those HPVs of knownand surgery with radiotherapy, with or without high oncogenic potential24.adjunctive chemotherapy. All of these cause tremen-dous physical, emotional and psychosocial disruption,but significantly worse health-related quality of life is Age distribution. Age-specific incidence and mortalityexperienced by patients who require both surgery and rates of oral cavity cancer in India are illustrated inradiotherapy20–22. Although adjunctive chemotherapy Figure 6. Although oral cancer has traditionally beencan lengthen survival, it is associated with consider- thought of as a disease mainly affecting people ofable toxicity and uniformly effective agents and older ages, a substantial proportion of cases arise inregimes have yet to be identified. the third and fourth decades of life. Increasing incidence with age has generally been attributed to indiscriminate substance abuse, particu-Analytic epidemiology larly of tobacco and tobacco-related products, over aAetiology considerable period of time11, which allows multiple genetic damage to accrue. Further, immune surveil-The causes of malignant transformation of the oral lance diminishes with age27. In the West, the risingepithelium and the processes of invasion and metasta- incidence of oral cancers in younger age groups refers18 © 2012 FDI World Dental Federation
  • 8. The epidemic of oral cancer in India 60 all forms of tobacco common in India are highly toxic to multiple body systems. There is an extensive 50 Incidence: Male literature on the wide range of tobacco products Mortality: Male used in India. These are summarised, in the contextRate per 100,000 population Incidence: Female of a thoughtful approach to tobacco control in 40 Mortality: Female India, in the Report of the Ministry of Health and Family Welfare, 200431. Tobacco use is, indeed, the 30 single most important modifiable risk factor for oral cancer; a meta-analysis of data available worldwide 20 has determined the relative risk (RR) for oral cancer in current smokers to be 3.43 [95% confidence 10 interval (CI) 2.37–4.94]32. As with all environmental carcinogens, there is a dose–response relationship. 0 0- 15- 40- 45- 50- 55- 60- 65- 70- 75+ Tobacco and alcohol consumption is identified as a Age, years behavioural risk factor in 75–95% of cases of oral cancer in India33.Figure 6. Age-specific rates of cancer of the lip and oral cavity (ICD-10 codes: C00–C08) in India, according to GLOBOCAN data for 2008. According to the National Family Health Survey Source: http://ci5.iarc.fr/CI5plus/ci5plus. (NFHS-3) conducted in 2005–2006, in people aged 15 –49 years, tobacco use is much more prevalent amongto disease of the base of tongue and oropharynx, and men than among women; 57% of men and 11% ofappears to be related to HPV infection. However, in women use some form of tobacco. One third of menhigh-incidence countries, such as India, high tobacco smoke cigarettes or other tobacco products34. In ruralconsumption that begins at a relatively young age India, and amongst those of lower socioeconomic sta-undoubtedly contributes5,11. tus, hand-made products such as bidis and a variety of cheroots and cigars are common.Gender differences. Males are, overall, at higher risk.However, the highest incidence rates for oral cancer Beedi/bidi smoking. It is estimated that overin the world are seen amongst some subpopulations 100 million Indians smoke bidis35. The bidi representsof women in southern India, and in emigrant the most popular form of tobacco and an age-oldpopulations from this area, such as female plantation form of indigenous smoking widely practised,workers in Malaysia28. This reflects the practice of particularly in southern India, by people of lowerheavy pan chewing (piper betel leaf filled with sliced socioeconomic status36,37.areca nut, lime, catechu and other spices chewed with Bidis contain about 0.2–0.5 g of raw, dried andor without tobacco), poor nutrition and poor oral crushed tobacco flakes, naturally cured, wrapped in ahygiene. Another group of women at particular risk temburni leaf; they deliver as much as 45–50 mg ofare those habituated to smoking with the burning end tar, compared with the 18–28 mg delivered in anof a cheroot or cigarette held inside the mouth in the Indian factory-produced cigarette37. A three-foldmanner practised in parts of Andhra Pradesh29. This increased risk for oral cancer in bidi smokers wasresults in a high incidence of palatal cancer, which is determined by a meta-analysis of 10 case–controlotherwise comparatively rare. studies from India by Rahman et al.38 This risk is comparable with that of cigarette smokers36.Religion. Although Hindus carry the highest burdenof oral cancer throughout India, there are no national Smokeless tobacco. Smokeless tobacco is consumeddata to explain this beyond the fact that this religious/ predominantly by chewing it as an ingredient in pan/cultural group represents the majority of the paan/betel quid, packaged pan masala or gutkha (apopulation and that many of its members are of low chewable tobacco containing areca nut), and mishri (asocioeconomic status and engage heavily in dangerous powdered tobacco rubbed on the gums aslifestyle practices30. toothpaste)39. The use of smokeless tobacco is socially acceptable, especially in eastern, northern andTobacco. All types of tobacco are not the same: northeastern parts of the country31. The use of new,tobacco varies widely by botanical type, processing commercially available blends of pan masala andand mode of use. Unsurprisingly, it varies in toxicity, gutkha is increasing, not only among men, but alsoincluding in carcinogenicity. That said, there is no among children, teenagers and women40. A cohortsuch thing as safe tobacco and, as far as is known, study from Kerala found that tobacco chewing© 2012 FDI World Dental Federation 19
  • 9. Gupta et al.increases the risk for cancers of the gum and mouth regard to risk factors, clinical features, sensitivity toby nearly five-fold36. treatment and prognosis50. A multicentre study con- ducted in the USA has shown that patients with HPV- positive tumours have a 50–80% reduction in risk forAreca nut. Areca nut is the fourth most commonly treatment failure compared with HPV-negativeused psychoactive substance in the world after patients51.caffeine, nicotine and alcohol41. It contains arecoline Few data are available regarding the incidence ofand 3-(methylnitrosamino) propionitrile, and lime HPV16- and 18-induced oral cancers in the Indianprovides reactive oxygen radicals, each of which scenario, except some derived from studies of smallcontribute to oral carcinogenesis26. Supari, which sample size52. Balaram et al. reported prevalences ofconsists of small roasted and flavoured pieces of areca 42% and 47% for HPV16 and HPV18, respectively,nut, often prepared commercially, is popularly served in a study of oral cancers in Indian betel quid chew-to guests after meals in northern India. In ers53. The prevalence of HPV-positive cases hasnortheastern parts of India, fermented areca nut shown significant geographical variation: 34% of oralcalled ‘tamul’ is common. In Gujarat, ‘mawa’, which SCC patients were identified as HPV-positive in east-consists of thin shavings of areca nut with the ern India, compared with 67% in southern India andaddition of some tobacco and slaked lime, is very 15% in western India53. The literature suggests thatcommonly used by youth. Areca nut, in combination HPV infection is relatively more common in oral SCCwith tobacco in the form of gutka, and without patients in India than in those from other countries;tobacco in the form of pan masala, is widely available for example, only 23% of Japanese patients, 8–20%in prepackaged forms and is promoted as a safe of American patients and 19% of Dutch patients areproduct and even as a mouth freshener42. However, HPV-positive54. All such data, however, should begutka is carcinogenic and areca nut in all its forms is interpreted cautiously: the detection of virus is verythe major cause of the potentially malignant disorder technique-dependent; there is a real risk for contami-oral submucous fibrosis43. Areca nut chewing is a nation, especially where highly sensitive polymerasesocially acceptable and widely practised habit chain reaction methods are employed, and the pres-amongst youth and even children, especially in ence of virus does not itself prove causality.Maharashtra, Gujarat and Bihar41. DISCUSSIONAlcohol drinkingThe effects of smoking and alcohol consumption on Socioeconomic determinantsthe risk for oral cancer are strongly synergestic44. In a All over the world, oral cancer is more prevalentstudy from south India, a multiplicative interaction amongst people of low socioeconomic status, partlybetween the consumption of alcohol and tobacco because tobacco use in any form is more common inproducts, respectively, was observed to induce a 24- these population groups and such patients do less wellfold increase in risk for oral cancer45. A cohort study because they have less access to care55. Case–controlconducted in Kerala revealed that approximately 80% studies from India reveal that lower education levelsof alcohol-dependent patients smoke cigarettes29. are related to increased risk for oral cancer19. Isolated studies conducted in small townships in India have shown that level of education is closely related toHuman papillomavirus awareness of oral cancer and its risk factors10.Since the first report of an association of HPV with There are large gaps in current knowledge of theSCC in 197746, numerous studies have explored the precise socioeconomic determinants of oral cancer.evidence for HPV in the aetiology of oral cancer. The Positive changes in the social determinants of healthassociation is strongest for cancer of the tonsil and would lead to improvements in health equity.other parts of the oropharynx. Positivity for HPV, Approaches that take into account the principles ofspecifically carriage of the high-risk genotypes HPV16 the Ottawa Charter for Health Promotion, adopt aand HPV18, has come to be associated with a specific common risk factor and a multi-sector coordinatedsubgroup of oropharyngeal SCCs that arise preferen- approach are needed.tially among individuals with no history of significantlongterm consumption of tobacco and alcohol and Current interventions for oral cancer control in Indiahave a favourable outcome attributable to anincreased sensitivity towards radiotherapy47–49. India has several world-leading cancer treatment cen-Human papillomavirus-associated oropharyngeal can- tres and clinical services are available across thecer thus differs from other head and neck SCCs with nation. Because of the high case load, exceptional20 © 2012 FDI World Dental Federation
  • 10. The epidemic of oral cancer in Indiaexperience and expertise exists in head and neck porations and governments, which would deliveroncology in many places. However, both access to action through policy development and the provisionthese and the facilities available – of both staff and of health care at individual, community and nationalequipment – are highly variable. Effective prevention levels. The Mumbai Declaration builds on the Creteis necessary to stem the epidemic. Declaration of 200561 and a declaration agreed by the The National Tobacco Control Programme, admin- Indian Association of Oral and Maxillofacial Patholo-istered by the Ministry of Health and Family Welfare gists (IAOMP) at an international congress held inat the national level, is presently predominantly con- Chennai in December 2010.fined to information, education and communicationcampaigns, the establishment of tobacco testing labo- Primary preventionratories to build regulatory capacity, and the mains-treaming of programme components under the Primary prevention achieved by the modification ofNational Rural Health Mission. However, these initia- risk factors is the most cost-effective approach62. Thetives so far have low visibility56. The Report on highest priority should be given to tobacco control.Tobacco Control in India31, published in 2004, makes Special attention should be directed towards control-cogent recommendations to central and state govern- ling the use of smokeless tobacco, which is rapidlyments, civil society, health professionals, international increasing among women and youth. Legislative mea-organisations and research scientists, and proposes sures are needed and should build on the success ofmulti-sector action. India was an early signatory, in such approaches to reduce smoking across much of2004, to the Framework Convention on Tobacco the world. These should include: the increased taxa-Control57 and indeed represented the seventh country tion of all tobacco and alcohol products and the pro-in the world to ratify this. However, legislation vision of targeted funding for oral cancer preventionremains weak and the tobacco industry continues to programmes through this enhanced tax collection; thehave significant lobbying influence in, for example, enforcement of laws on youth access to tobacco anddelaying the implementation of regulations to man- alcohol; the prohibition of all advertising and promo-date the printing of pictorial warnings on tobacco tional activities by the tobacco industry, and thepackages. State government bans against smokeless prominent inclusion of strong pictorial warnings intobacco have come and gone. existing written warnings on the labels of tobacco and The initiatives of the Indian Dental Association are alcohol products.commended here. Its Tobacco Intervention Initiative Culturally acceptable health promotion and aware-and S.P.O.T. (spot and prevent oral cancer trauma) ness programmes that address the myths and miscon-centres, established under the aegis of the Oral Cancer ceptions associated with cancer and related stigmaFoundation (OCF), are admirable and will, it is should be introduced on a large scale all over thehoped, be rolled out across the entire country in due country and should be particularly targeted towardscourse58. Synergising these with the activities of all groups identified as susceptible, such as youth andother stakeholders will be important. women63. The participation of non-governmental organisa- tions, medical and dental professionals, and behavio-Proposed strategies for oral cancer control in India ural scientists is required in advocacy to informPrimary prevention, health education, early detection political leaders and government about the expectedand the provision of the earliest possible therapeutic benefits of tobacco control, the safe use of alcohol,intervention are all essential components of an accept- and programmes to increase awareness of the earlyable oral cancer control policy59. Such a policy should warning signs of oral cancer. These programmesbe implemented in the form of a well-administered should be embedded into a common risk factornational oral cancer control programme. It should approach for multiple health disorders rather thantake into consideration the large variations across applied in isolation7,10. This is consistent with theIndian states in socioeconomic and sociocultural back- approach of the Lancet Non-Communicable Diseasegrounds, languages, behaviours and lifestyles. Longi- (NCD) Action Group and the NCD Alliance64. It istudinal monitoring and evaluation of the programme reassuring that the United Nations recognises the needwould be essential. for a new approach at the highest political level. The Such a programme could be based on the Mumbai declaration from the NCD Summit held in NovemberDeclaration60. This proposes a 5-year action plan with 2011 called for a multi-pronged campaign by govern-specific targets for bringing down the incidence and ments, industry and civil society to develop, by 2013,mortality rates associated with oral cancer. It pro- the plans needed to curb the risk factors behind theposes a strategic alliance of many stakeholders, four groups of NCDs: cardiovascular diseases; can-including individuals, communities, organisations, cor- cers; chronic respiratory diseases, and diabetes. Article© 2012 FDI World Dental Federation 21
  • 11. Gupta et al.19 of the Political Declaration stipulates that member Secondary prevention: screeningstates recognise ‘…that renal, oral and eye diseases Screening for oral cancer by visual examination of thepose a major health burden for many countries and mouth has been researched in several countries, usuallythat these diseases share common risk factors and can with the conclusion that it is not cost-effective. Thebenefit from common responses to non-communicable major reason for this is the low prevalence of disease indiseases’65. Clearly, this includes oral cancer. The the societies and populations studied. The case is theo-political will thus demonstrated provides encourage- retically stronger in populations in which the diseasement. The FDI World Dental Federation will be a occurs at a high prevalence, such as in India. Addition-major partner in taking these initiatives forward65. ally there is, in the majority of cases in India, a recogni- Health promotion programmes that advocate sable precursory phase. The most meaningful work tohealthy lifestyles and focus on diets rich in vegetables, date was carried out by the Trivandrum Oral Cancerfruits, fibre, milk (to some extent), antioxidants and Screening Programme. This uses visual inspection withappropriate physical activity should be protective sufficient light and has demonstrated a reduction inagainst oral cancer66,67. More multicentre randomised mortality at modest cost8,70. The sensitivity and speci-controlled trials of dietary supplementation for per- ficity of oral visual inspection in the detection ofsons with OPMDs are required to assess the efficacy OPMD and oral cancer by specially trained primaryof vitamins, retinoids and carotenoids7,68. Identifica- health care workers were 94.3% and 99.3%, respec-tion of OPMDs should be encouraged, documented tively, and a high level of agreement between theseand become part of routine dental examinations in all workers and physicians was observed8,71.government and private clinics23. Patients in whom findings are positive should be The establishment of a database of educational referred to health professionals for expert clinicalmaterials related to oral cancer and OPMDs – for use opinion, support with habit cessation, biopsy if indi-by both professionals and the public – in the many cated in the judgement of the professional, and furthernecessary languages and applicable across all cultural management24. Although the most appropriate profes-groups would be helpful. sional workforce resides within the dental profession, The role of HPV should be tackled in culturally others can be trained, and screening for OPMD andacceptable health programmes promoting safe sexual oral cancer should be conducted in conjunction withpractices69. These should be part of existing – and, it screening by other programmes for other cancers andis hoped, expanding – social marketing campaigns for infections, including HIV and other sexually transmit-the prevention of cancer of the uterine cervix and of ted diseases, as recommended by the ‘Closing thesexually transmitted infections, including human Cancer Divide’63 report and endorsed by an editorialimmunodeficiency virus (HIV). Formal links should be published recently in the Lancet72.established with government agencies and pharmaceu-tical companies engaged in HPV vaccine trials for theprevention of cervical cancer to monitor potential Access to care: tertiary preventionbenefits over time in reducing the incidence of head Survival rates, especially in patients with advanced oraland neck cancers7. cancer at diagnosis, have changed little over recent dec- Education campaigns are needed to raise public ades, except in the most advanced high-volume centresawareness about oral cancer and its links with in the world. Facilities for accurate staging, includingtobacco and alcohol consumption. These might be advanced imaging, and experienced multidisciplinaryeffectively supported by prominent public figures from teams can improve longterm survival and quality ofthe sports and film sectors and other distinguished life7. More of these are needed across India, althoughpersons. Oral cancer victims and survivors may be treatment will never represent the route to reduced inci-valuable in such public campaigns. dence. Systematic, cost-effective, equitable and evi- dence-based treatment guidelines should be spreadProfessional knowledge and behaviours from the existing centres of excellence across the land. The training and continuing education of allKey needs include: the promotion of instruction in streams of health care professionals involved in thecontrolling tobacco and alcohol use at all levels of management of oral cancer should be enhanced.training in dental, medical, nursing and related health Excellent clinicians capable of leading such initiativescare disciplines; the promotion of routine assessment are employed in many centres in India today.of all patients for tobacco and alcohol intake by allclinical disciplines, and the promotion of training of Pain control and palliative careclinicians, especially at the primary health care level,to enable them to detect oral cancer and precancerous Oral cancer causes severe physical, psychosocial andlesions at the earliest possible stage. spiritual pain to patients and their families. Trained22 © 2012 FDI World Dental Federation
  • 12. The epidemic of oral cancer in Indiastaff and facilities for caring for terminally ill patients To summarise, efforts towards the control of oral can-and their families are required across the nation63,69: cer in India will benefit from an approach based on com-many such already exist, provided by government and mon risk factors that integrates oral health with overallby non-government organisations, but their availabil- health care and applies existing knowledge in a whole-ity is patchy. society approach. Ever-present funding constraints and lack of political will in the field of health care must be challenged by continued and innovative advocacy.Data storage and documentationAt present, cancer registration in India is voluntary. AcknowledgementThe ICMR network of cancer registries is doing excel-lent work, but this should be expanded to ensure We are grateful to all our colleagues in India for theirgreater population coverage: for example, no registries collaboration over many years.exist in the populous and relatively poor states of Ut-tar Pradesh, Bihar and Orissa. Legislative support formandatory registration is required, along with an Conflicts of interestincrease in resources to permit not only the more None declared.complete capture of cases, but to assist with follow-up. Currently, there is no system of registries in India REFERENCESfor recording cases of OPMD. We strongly recom-mend that such a system be established across the 1. Chiba I. Prevention of betel quid chewers oral cancer in the Asian-Pacific area. Asia Pac J Cancer Prev 2001 2: 263–269.nation. Given that India has well over 200 dental col- 2. Petersen PE. 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