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

REV IEW ART ICLE

Oral cancer in India continues in epidemic proportions:evidence base and policy initiatives

Bhawna Gupta1, Anura Ariyawardana2,3 and Newell W. Johnson2

1Epidemiologist, 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, HPV

The Indian subcontinent, especially India itself becauseof its large population, has long been regarded as theglobal epicentre of oral cancer. The malady recognisedby the world as oral cancer was first described in theSushruta Samhita, a treatise on Indian surgery writtenin Sanskrit around 600 BC1. The World Health Orga-nization (WHO) regards oral cancer as a major publichealth challenge in India2. The burden it imposes, interms of incidence, mortality, survival and the determi-nants of disease, as well as the inevitable stretching oflimited health care resources, is not fully appreciated,particularly in India. There is wide variation in the glo-bal burden of this disease, with incidences in India andacross South and Southeast Asia amongst the highest inthe world3. Incidence is also increasing elsewhere, suchas in parts of Western and Eastern Europe, Latin Amer-ica and the Pacific regions3.Malignant neoplasms of the lip, oral cavity and oro-

pharynx [International Classification of Diseases (ICD)-10 codes: C00–C14], excluding other pharyngeal sites(C11–C13), are often grouped together4. They havecommon risk factors and, to some extent, behaviours.

Collectively, these conditions represent the sixth mostcommon type of cancer in the world. Annual estimatedglobal incidences amount to around 275,000 cases oforal and 130,300 cases of pharyngeal cancers excludingcancers of the nasopharynx, two thirds of which occurin developing countries5. In this paper, we define oralcancer as any malignant neoplasm occurring on the lipsor within the mouth/oral cavity, including on the ton-gue (ICD-10 codes: C00–C06)6. Wherever possible, wehave excluded diseases of the major salivary glands(C07, C08) and nasopharynx (C11) because of their dif-ferent biology4. Diseases of the oropharynx (C10), pyri-form sinus (C12) and hypopharynx (C13) have somecommonality in risk factors and behaviour and there-fore data for disease in these sites are given where rele-vant. Because of inconsistencies in the groupings usedby different authors and databases, we have striven tolist the sites included whenever data are given.Today, 90–95% of all new cases of oral malignancy

in most populations, including that in India, are squa-mous cell carcinomas (SCC) arising from liningmucosa7. Squamous cell carcinomas of the oro- and

12 © 2012 FDI World Dental Federation

International Dental Journal 2013; 63: 12–25

doi: 10.1111/j.1875-595x.2012.00131.x

hypopharynx are increasing in many countries, partic-ularly in the West. Many cases are related to the tra-ditional risk factors of smoking and heavy alcoholconsumption, and others to infection with humanpapillomavirus (HPV). However, in the Indian con-text, oral cancer itself is most common, and its aetiol-ogy is dominated by tobacco use, especially ofsmokeless tobacco, areca [betel] nut consumption andalcohol abuse, all of which frequently act in the pres-ence of poor diet and poor dental health. This is apreventable disease: this paper focuses on the publichealth challenge presented by oral cancer in India.

MATERIALS AND METHODS

Search strategy

Our extensive literature review screened the PubMed,EMBASE, CINAHL (Cumulative Index to Nursing andAllied Health Literature), Cochrane Library and Coch-rane Oral Health Group’s Trials Register databases upto October 2011 for literature published in Englishonly, irrespective of publication date. Main searchterms were: ‘oral cancer’; ‘mouth cancer’; ‘risk factors’;‘policy’; ‘interventions’ and ‘treatment’, with ‘India’.Supplementary key words were: ‘tobacco’; ‘alcohol’;‘betel nut’; ‘areca nut chewing’; ‘socioeconomic deter-minants’; ‘oral cancer epidemiology’; ‘oral cancer pre-vention’, and ‘oral cancer treatment’. A total of 793articles were retrieved, for which the titles and abstractswere evaluated. This resulted in the retention of 131articles which were read in full; 32 of these wereexcluded for not reporting relevant outcomes.The ‘related articles’ links and the references of the

articles reviewed were hand-searched for additionalreferences. This resulted in the identification of a fur-ther 140 papers.Papers excluded were those in which some confusion

over the anatomical sites of origin of the malignanciesdescribed was apparent, papers in which the numbersof cases were small and the data were judged to be notgeneralisable, and papers reporting studies in which theanalytical methods were judged to be faulty. A total of99 papers were fully evaluated. The most relevant datawere found in official publications of the Indian Coun-cil of Medical Research (ICMR), derived from the indi-vidual registries maintained across the nation(Figure 1). We reviewed the following databases andwebsites: GLOBOCAN 2008; National Centre for Dis-ease Informatics and Research (http://www.ncdirindia.org/); National Cancer Registry Programme (http://www.icmr.nic.in/ncrp/cancer_reg.htm); InternationalAgency for Research on Cancer (IARC) (http://www.iarc.fr/); International Head and Neck Epidemiology(http://inhance.iarc.fr/index.php); Centers for DiseaseControl and Prevention (http://www.cdc.gov), and the

IARC Screening Group (http://screening.iarc.fr/atlas-oral.php?lang-1). We also reviewed the textbooksHeadand Neck Cancer: Multimodality Management (BernierJ, ed., Springer/Humana Press, 2011) and Oral Cancer(Shah JP, Johnson NW, Batsakis JG, eds., MartinDunitz, 2003).

RESULTS

Descriptive epidemiology

Global burden of oral cancer

Estimated incidence, mortality and 5-year prevalencesof lip and oral cavity cancer, as estimated byGLOBOCAN 2008, for the whole world and forIndia, are summarised in Table 1. Two thirds of theglobal burden of these cancers occurs in developingcountries and the Indian subcontinent accounts fornearly one third of global incidence8.Although the incidence rates given for oral cancer

for all ages (0–75 years) are lower in India [weightedage-standardised rate (ASR-w) for both sexes com-bined: 7.5 per 100,000 per annum] than in someother developing countries, notably Melanesia (ASR-w 17.8), Maldives, Taiwan, Brunei and Sri Lanka,India contributes the highest number of new casesbecause of its huge population. Over five people diefrom oral cancer every hour every day in India andalmost the same number die from cancer of the oro-pharynx and hypopharynx3.

Burden of oral cancer in India

Oral cancer (ICD-10 codes: C01–C06) ranks amongstthe three most common cancers in India and in someareas accounts for almost 40% of total cancerdeaths9. Figure 2 shows estimated incidences andmortality in men and women of all ages in India.Approximately 70,000 new cases and more than48,000 oral cancer-related deaths occur yearly10. Inmost regions of India, oral cancer is the second mostcommon malignancy diagnosed in men, accountingfor up to 20% of cancers, and the fourth most com-mon in women (Figure 3)3,11.Note, however, that GLOBOCAN data for India as

a whole are extrapolations based on the estimatedpopulation of the nation and data from regional can-cer registries. As will become evident in this text,there is considerable variation among registries in thecases recorded. Further, as cancer registration is notcompulsory in India, it is probable that the true inci-dence and mortality are much higher: many cases gounrecorded and/or are lost to follow-up12.Over 100,000 cases of oral cancer are cur-

rently recorded on cancer registers across India3.

© 2012 FDI World Dental Federation 13

The epidemic of oral cancer in India

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 2008

Population World More developed regions Less developed regions South Central Asia India

IncidenceCases, n* 263,020 91,148 171,872 97,623 69,820ASR-w, %† 3.8 4.4 3.6 7.4 7.5Cumulative risk, %‡ 0.44 0.51 0.42 0.88 0.89

MortalityCases, n* 127,654 30,689 96,965 63,610 47,653ASR-w, %† 1.8 1.4 2.0 4.9 5.2Cumulative risk, %‡ 0.22 0.16 0.24 0.59 0.61

5-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/).


Gupta et al.

The overall incidence derived from Indian databasesmay be as high as 19 per 100,000 per annum3,13.According to the National Cancer Registry Pro-gramme (NCRP), Bhopal district has the highest age-adjusted incidence rate (AAR) in the world for cancersof both the tongue (ICD-10 codes: C01, C02) (10.9per 100,000) and mouth (ICD-10 codes: C03–C06)(9.6 per 100,000) among males (Figure 4). Amongfemales, Bhopal has the second highest AAR (7.2 per100,000) for cancer of the mouth (Figure 4)14. Data

on the AAR of tongue cancer amongst females arevery scarce.

Projected burden of oral cancer in India by 2020.Numbers of oral cancer cases (IDC-10 codes: C00–C08) and deaths in India predicted by the ICMRby the year 2020 are presented in Figure 515. Thissubstantial rise places a severe burden on thenation. The cumulative lifetime risk for mortality

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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 thehighest 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).



from lip or oral cavity cancer in India for malesand females aged 0–74 years is 61%3.

Survival. Survival for each cancer site (all clinicalstages included) is described in terms of 5-year age-standardised relative survival16. In most parts of the

world, mean overall 5-year survival rates in oralcancer are still hovering around 50% and rates inIndia are estimated to be 40–45%17. Metastasis toregional lymph nodes is the single most importantprognostic factor in predicting local and distantfailure, as well as survival. Significantly, 10–30% ofpatients with oral cancer subsequently develop

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Figure 3. Most frequent cancers among (a) males and (b) females in India according to GLOBOCAN data for 2008. ‘Lip, oral cavity’ data refer toICD-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 nonational 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 mortalitywas 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’].


Gupta et al.

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Figure 4. (a) Comparisons of age-adjusted incidence rates derived from population-based cancer registries (PBCRs) under the Indian National Cancer RegistryProgramme (INCRP) and international equivalents, for cancer of the tongue (ICD-10 codes: C01, C02) in males in 2001–2002. Globally, the highest rates are

seen in Bhopal in central India and Ahmedabad in western India. Chennai, in the south, Delhi, in the north, andMumbai, in the west, also show high rates. Thesedata 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.



second primary tumours of the aerodigestivetract18.Marked differences in survival have been noted among

rural (Barshi), semi-urban (Karunagappally) and smallurban (Bhopal) registries in India, whereas differencesare small between the registries of the major cities ofChennai andMumbai, wheremore developed and acces-sible health care services are available16. Poor survivalrates can also be attributed to the fact that half of the oralcancer cases in the nation are diagnosed at advancedstages (stages III and IV) because patient’s delay in seek-ingmedical care and acceptance of treatment is low5,19.Multiple treatment options are available in many

centres. These include surgery or radiotherapy alone,and surgery with radiotherapy, with or withoutadjunctive chemotherapy. All of these cause tremen-dous physical, emotional and psychosocial disruption,but significantly worse health-related quality of life isexperienced by patients who require both surgery andradiotherapy20–22. Although adjunctive chemotherapycan lengthen survival, it is associated with consider-able toxicity and uniformly effective agents andregimes have yet to be identified.

Analytic epidemiology

Aetiology

The causes of malignant transformation of the oralepithelium and the processes of invasion and metasta-

sis are as complex as for any other anatomical site.Genetic predisposition plays a minor role expressedthrough polymorphisms in carcinogen-metabolisingenzymes, the expression of oncogenes and oncosup-pressor genes, and DNA repair genes23. There isincreasing evidence of the importance of chronicinflammation, alterations in host immunity, metabo-lism and neo-angiogenesis, all of which may be trig-gered or enhanced by viruses, radiation, chemicals(notably from tobacco and alcoholic beverages), hor-mones, nutrients or physical irritants24.

Oral potentially malignant disorders

In South Asia, the majority of oral cancers arise frompre-existing longstanding lesions, now termed ‘oralpotentially malignant disorders’ (OPMDs)23 in recogni-tion of the fact that systemic, cellular and molecularchanges are much wider than any particular macro-scopically visible oral lesion. In India, tobacco is themajor aetiological agent, producing visible lesions ofwhich so-called leukoplakia is the most common. Thisassociation has led to the aphorism ‘cancer is wheretobacco is’25. This knowledge explains the focus for theprimary prevention of oral cancer on population-basedstrategies and on the early detection of OPMDs; habitintervention and follow-up are regarded as secondaryprevention strategies conducted on an individual basis.

Major risk factors. Risk factors may vary for differentcultural and socioeconomic groups. However,established risk factors for oral cancer in the Indianpopulation include: tobacco in all its forms (smoked,chewed, used as oral snuff); the chewing of betel quid(pan/paan); the heavy consumption of alcohol, andthe presence of an OPMD24,26. Other contributory orpredisposing factors include dietary deficiencies,particularly of vitamins A, C and E and iron, andviral infections, particularly by those HPVs of knownhigh oncogenic potential24.

Age distribution. Age-specific incidence and mortalityrates of oral cavity cancer in India are illustrated inFigure 6. Although oral cancer has traditionally beenthought of as a disease mainly affecting people ofolder ages, a substantial proportion of cases arise inthe third and fourth decades of life.Increasing incidence with age has generally been

attributed to indiscriminate substance abuse, particu-larly of tobacco and tobacco-related products, over aconsiderable period of time11, which allows multiplegenetic damage to accrue. Further, immune surveil-lance diminishes with age27. In the West, the risingincidence of oral cancers in younger age groups refers

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Figure 5. Projected incidences of cancer of the mouth and tongue (ICD-10codes: C01–C06) in males and females in India in 2008, 2009, 2010, 2015and 2020. Projections are derived from crude incidence rates generated bypopulation-based cancer registries at Bangalore, Barshi, Bhopal, Chennai,Delhi andMumbai (for 2001–2005). By 2020, a sharp increase in the num-ber of cases of mouth cancer in males is expected, with a slower increase infemales. The burden of cancer of the tongue in both males and females will

also rise by 2020. Source: Indian Council of Medical Research15.


Gupta et al.

to disease of the base of tongue and oropharynx, andappears to be related to HPV infection. However, inhigh-incidence countries, such as India, high tobaccoconsumption that begins at a relatively young ageundoubtedly contributes5,11.

Gender differences. Males are, overall, at higher risk.However, the highest incidence rates for oral cancerin the world are seen amongst some subpopulationsof women in southern India, and in emigrantpopulations from this area, such as female plantationworkers in Malaysia28. This reflects the practice ofheavy pan chewing (piper betel leaf filled with slicedareca nut, lime, catechu and other spices chewed withor without tobacco), poor nutrition and poor oralhygiene. Another group of women at particular riskare those habituated to smoking with the burning endof a cheroot or cigarette held inside the mouth in themanner practised in parts of Andhra Pradesh29. Thisresults in a high incidence of palatal cancer, which isotherwise comparatively rare.

Religion. Although Hindus carry the highest burdenof oral cancer throughout India, there are no nationaldata to explain this beyond the fact that this religious/cultural group represents the majority of thepopulation and that many of its members are of lowsocioeconomic status and engage heavily in dangerouslifestyle practices30.

Tobacco. All types of tobacco are not the same:tobacco varies widely by botanical type, processingand mode of use. Unsurprisingly, it varies in toxicity,including in carcinogenicity. That said, there is nosuch thing as safe tobacco and, as far as is known,

all forms of tobacco common in India are highlytoxic to multiple body systems. There is an extensiveliterature on the wide range of tobacco productsused in India. These are summarised, in the contextof a thoughtful approach to tobacco control inIndia, in the Report of the Ministry of Health andFamily Welfare, 200431. Tobacco use is, indeed, thesingle most important modifiable risk factor for oralcancer; a meta-analysis of data available worldwidehas determined the relative risk (RR) for oral cancerin current smokers to be 3.43 [95% confidenceinterval (CI) 2.37–4.94]32. As with all environmentalcarcinogens, there is a dose–response relationship.Tobacco and alcohol consumption is identified as abehavioural risk factor in 75–95% of cases of oralcancer in India33.According to the National Family Health Survey

(NFHS-3) conducted in 2005–2006, in people aged 15–49 years, tobacco use is much more prevalent amongmen than among women; 57% of men and 11% ofwomen use some form of tobacco. One third of mensmoke cigarettes or other tobacco products34. In ruralIndia, and amongst those of lower socioeconomic sta-tus, hand-made products such as bidis and a varietyof cheroots and cigars are common.

Beedi/bidi smoking. It is estimated that over100 million Indians smoke bidis35. The bidi representsthe most popular form of tobacco and an age-oldform of indigenous smoking widely practised,particularly in southern India, by people of lowersocioeconomic status36,37.Bidis contain about 0.2–0.5 g of raw, dried and

crushed tobacco flakes, naturally cured, wrapped in atemburni leaf; they deliver as much as 45–50 mg oftar, compared with the 18–28 mg delivered in anIndian factory-produced cigarette37. A three-foldincreased risk for oral cancer in bidi smokers wasdetermined by a meta-analysis of 10 case–controlstudies from India by Rahman et al.38 This risk iscomparable with that of cigarette smokers36.

Smokeless tobacco. Smokeless tobacco is consumedpredominantly by chewing it as an ingredient in pan/paan/betel quid, packaged pan masala or gutkha (achewable tobacco containing areca nut), and mishri (apowdered tobacco rubbed on the gums astoothpaste)39. The use of smokeless tobacco is sociallyacceptable, especially in eastern, northern andnortheastern parts of the country31. The use of new,commercially available blends of pan masala andgutkha is increasing, not only among men, but alsoamong children, teenagers and women40. A cohortstudy from Kerala found that tobacco chewing

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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.

Source: http://ci5.iarc.fr/CI5plus/ci5plus.



increases the risk for cancers of the gum and mouthby nearly five-fold36.

Areca nut. Areca nut is the fourth most commonlyused psychoactive substance in the world aftercaffeine, nicotine and alcohol41. It contains arecolineand 3-(methylnitrosamino) propionitrile, and limeprovides reactive oxygen radicals, each of whichcontribute to oral carcinogenesis26. Supari, whichconsists of small roasted and flavoured pieces of arecanut, often prepared commercially, is popularly servedto guests after meals in northern India. Innortheastern parts of India, fermented areca nutcalled ‘tamul’ is common. In Gujarat, ‘mawa’, whichconsists of thin shavings of areca nut with theaddition of some tobacco and slaked lime, is verycommonly used by youth. Areca nut, in combinationwith tobacco in the form of gutka, and withouttobacco in the form of pan masala, is widely availablein prepackaged forms and is promoted as a safeproduct and even as a mouth freshener42. However,gutka is carcinogenic and areca nut in all its forms isthe major cause of the potentially malignant disorderoral submucous fibrosis43. Areca nut chewing is asocially acceptable and widely practised habitamongst youth and even children, especially inMaharashtra, Gujarat and Bihar41.

Alcohol drinking

The effects of smoking and alcohol consumption onthe risk for oral cancer are strongly synergestic44. In astudy from south India, a multiplicative interactionbetween the consumption of alcohol and tobaccoproducts, respectively, was observed to induce a 24-fold increase in risk for oral cancer45. A cohort studyconducted in Kerala revealed that approximately 80%of alcohol-dependent patients smoke cigarettes29.

Human papillomavirus

Since the first report of an association of HPV withSCC in 197746, numerous studies have explored theevidence for HPV in the aetiology of oral cancer. Theassociation is strongest for cancer of the tonsil andother parts of the oropharynx. Positivity for HPV,specifically carriage of the high-risk genotypes HPV16and HPV18, has come to be associated with a specificsubgroup of oropharyngeal SCCs that arise preferen-tially among individuals with no history of significantlongterm consumption of tobacco and alcohol andhave a favourable outcome attributable to anincreased sensitivity towards radiotherapy47–49.Human papillomavirus-associated oropharyngeal can-cer thus differs from other head and neck SCCs with

regard to risk factors, clinical features, sensitivity totreatment 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 fortreatment failure compared with HPV-negativepatients51.Few data are available regarding the incidence of

HPV16- and 18-induced oral cancers in the Indianscenario, except some derived from studies of smallsample size52. Balaram et al. reported prevalences of42% and 47% for HPV16 and HPV18, respectively,in a study of oral cancers in Indian betel quid chew-ers53. The prevalence of HPV-positive cases hasshown significant geographical variation: 34% of oralSCC patients were identified as HPV-positive in east-ern India, compared with 67% in southern India and15% in western India53. The literature suggests thatHPV infection is relatively more common in oral SCCpatients in India than in those from other countries;for example, only 23% of Japanese patients, 8–20%of American patients and 19% of Dutch patients areHPV-positive54. All such data, however, should beinterpreted cautiously: the detection of virus is verytechnique-dependent; there is a real risk for contami-nation, especially where highly sensitive polymerasechain reaction methods are employed, and the pres-ence of virus does not itself prove causality.

DISCUSSION

Socioeconomic determinants

All over the world, oral cancer is more prevalentamongst people of low socioeconomic status, partlybecause tobacco use in any form is more common inthese population groups and such patients do less wellbecause they have less access to care55. Case–controlstudies from India reveal that lower education levelsare related to increased risk for oral cancer19. Isolatedstudies conducted in small townships in India haveshown that level of education is closely related toawareness of oral cancer and its risk factors10.There are large gaps in current knowledge of the

precise socioeconomic determinants of oral cancer.Positive changes in the social determinants of healthwould lead to improvements in health equity.Approaches that take into account the principles ofthe Ottawa Charter for Health Promotion, adopt acommon risk factor and a multi-sector coordinatedapproach are needed.

Current interventions for oral cancer control in India

India has several world-leading cancer treatment cen-tres and clinical services are available across thenation. Because of the high case load, exceptional


Gupta et al.

experience and expertise exists in head and neckoncology in many places. However, both access tothese and the facilities available – of both staff andequipment – are highly variable. Effective preventionis necessary to stem the epidemic.The National Tobacco Control Programme, admin-

istered by the Ministry of Health and Family Welfareat the national level, is presently predominantly con-fined to information, education and communicationcampaigns, the establishment of tobacco testing labo-ratories to build regulatory capacity, and the mains-treaming of programme components under theNational Rural Health Mission. However, these initia-tives so far have low visibility56. The Report onTobacco Control in India31, published in 2004, makescogent recommendations to central and state govern-ments, civil society, health professionals, internationalorganisations and research scientists, and proposesmulti-sector action. India was an early signatory, in2004, to the Framework Convention on TobaccoControl57 and indeed represented the seventh countryin the world to ratify this. However, legislationremains weak and the tobacco industry continues tohave significant lobbying influence in, for example,delaying the implementation of regulations to man-date the printing of pictorial warnings on tobaccopackages. State government bans against smokelesstobacco have come and gone.The initiatives of the Indian Dental Association are

commended here. Its Tobacco Intervention Initiativeand S.P.O.T. (spot and prevent oral cancer trauma)centres, established under the aegis of the Oral CancerFoundation (OCF), are admirable and will, it ishoped, be rolled out across the entire country in duecourse58. Synergising these with the activities of allother stakeholders will be important.

Proposed strategies for oral cancer control in India

Primary prevention, health education, early detectionand the provision of the earliest possible therapeuticintervention are all essential components of an accept-able oral cancer control policy59. Such a policy shouldbe implemented in the form of a well-administerednational oral cancer control programme. It shouldtake into consideration the large variations acrossIndian states in socioeconomic and sociocultural back-grounds, languages, behaviours and lifestyles. Longi-tudinal monitoring and evaluation of the programmewould be essential.Such a programme could be based on the Mumbai

Declaration60. This proposes a 5-year action plan withspecific targets for bringing down the incidence andmortality rates associated with oral cancer. It pro-poses a strategic alliance of many stakeholders,including individuals, communities, organisations, cor-

porations and governments, which would deliveraction through policy development and the provisionof health care at individual, community and nationallevels. The Mumbai Declaration builds on the CreteDeclaration of 200561 and a declaration agreed by theIndian Association of Oral and Maxillofacial Patholo-gists (IAOMP) at an international congress held inChennai in December 2010.

Primary prevention

Primary prevention achieved by the modification ofrisk factors is the most cost-effective approach62. Thehighest priority should be given to tobacco control.Special attention should be directed towards control-ling the use of smokeless tobacco, which is rapidlyincreasing among women and youth. Legislative mea-sures are needed and should build on the success ofsuch approaches to reduce smoking across much ofthe world. These should include: the increased taxa-tion of all tobacco and alcohol products and the pro-vision of targeted funding for oral cancer preventionprogrammes through this enhanced tax collection; theenforcement of laws on youth access to tobacco andalcohol; the prohibition of all advertising and promo-tional activities by the tobacco industry, and theprominent inclusion of strong pictorial warnings inexisting written warnings on the labels of tobacco andalcohol products.Culturally acceptable health promotion and aware-

ness programmes that address the myths and miscon-ceptions associated with cancer and related stigmashould be introduced on a large scale all over thecountry and should be particularly targeted towardsgroups identified as susceptible, such as youth andwomen63.The participation of non-governmental organisa-

tions, medical and dental professionals, and behavio-ural scientists is required in advocacy to informpolitical leaders and government about the expectedbenefits of tobacco control, the safe use of alcohol,and programmes to increase awareness of the earlywarning signs of oral cancer. These programmesshould be embedded into a common risk factorapproach for multiple health disorders rather thanapplied in isolation7,10. This is consistent with theapproach of the Lancet Non-Communicable Disease(NCD) Action Group and the NCD Alliance64. It isreassuring that the United Nations recognises the needfor a new approach at the highest political level. Thedeclaration from the NCD Summit held in November2011 called for a multi-pronged campaign by govern-ments, industry and civil society to develop, by 2013,the plans needed to curb the risk factors behind thefour groups of NCDs: cardiovascular diseases; can-cers; chronic respiratory diseases, and diabetes. Article



19 of the Political Declaration stipulates that memberstates recognise ‘…that renal, oral and eye diseasespose a major health burden for many countries andthat these diseases share common risk factors and canbenefit from common responses to non-communicablediseases’65. Clearly, this includes oral cancer. Thepolitical will thus demonstrated provides encourage-ment. The FDI World Dental Federation will be amajor partner in taking these initiatives forward65.Health promotion programmes that advocate

healthy lifestyles and focus on diets rich in vegetables,fruits, fibre, milk (to some extent), antioxidants andappropriate physical activity should be protectiveagainst oral cancer66,67. More multicentre randomisedcontrolled trials of dietary supplementation for per-sons with OPMDs are required to assess the efficacyof vitamins, retinoids and carotenoids7,68. Identifica-tion of OPMDs should be encouraged, documentedand become part of routine dental examinations in allgovernment and private clinics23.The establishment of a database of educational

materials related to oral cancer and OPMDs – for useby both professionals and the public – in the manynecessary languages and applicable across all culturalgroups would be helpful.The role of HPV should be tackled in culturally

acceptable health programmes promoting safe sexualpractices69. These should be part of existing – and, itis hoped, expanding – social marketing campaigns forthe prevention of cancer of the uterine cervix and ofsexually transmitted infections, including humanimmunodeficiency virus (HIV). Formal links should beestablished with government agencies and pharmaceu-tical companies engaged in HPV vaccine trials for theprevention of cervical cancer to monitor potentialbenefits over time in reducing the incidence of headand neck cancers7.Education campaigns are needed to raise public

awareness about oral cancer and its links withtobacco and alcohol consumption. These might beeffectively supported by prominent public figures fromthe sports and film sectors and other distinguishedpersons. Oral cancer victims and survivors may bevaluable in such public campaigns.

Professional knowledge and behaviours

Key needs include: the promotion of instruction incontrolling tobacco and alcohol use at all levels oftraining in dental, medical, nursing and related healthcare disciplines; the promotion of routine assessmentof all patients for tobacco and alcohol intake by allclinical disciplines, and the promotion of training ofclinicians, especially at the primary health care level,to enable them to detect oral cancer and precancerouslesions at the earliest possible stage.

Secondary prevention: screening

Screening for oral cancer by visual examination of themouth has been researched in several countries, usuallywith the conclusion that it is not cost-effective. Themajor reason for this is the low prevalence of disease inthe societies and populations studied. The case is theo-retically stronger in populations in which the diseaseoccurs at a high prevalence, such as in India. Addition-ally there is, in the majority of cases in India, a recogni-sable precursory phase. The most meaningful work todate was carried out by the Trivandrum Oral CancerScreening Programme. This uses visual inspection withsufficient light and has demonstrated a reduction inmortality at modest cost8,70. The sensitivity and speci-ficity of oral visual inspection in the detection ofOPMD and oral cancer by specially trained primaryhealth care workers were 94.3% and 99.3%, respec-tively, and a high level of agreement between theseworkers and physicians was observed8,71.Patients in whom findings are positive should be

referred to health professionals for expert clinicalopinion, support with habit cessation, biopsy if indi-cated in the judgement of the professional, and furthermanagement24. Although the most appropriate profes-sional workforce resides within the dental profession,others can be trained, and screening for OPMD andoral cancer should be conducted in conjunction withscreening by other programmes for other cancers andinfections, including HIV and other sexually transmit-ted diseases, as recommended by the ‘Closing theCancer Divide’63 report and endorsed by an editorialpublished recently in the Lancet72.

Access to care: tertiary prevention

Survival rates, especially in patients with advanced oralcancer at diagnosis, have changed little over recent dec-ades, except in the most advanced high-volume centresin the world. Facilities for accurate staging, includingadvanced imaging, and experienced multidisciplinaryteams can improve longterm survival and quality oflife7. More of these are needed across India, althoughtreatment will never represent the route to reduced inci-dence. Systematic, cost-effective, equitable and evi-dence-based treatment guidelines should be spreadfrom the existing centres of excellence across the land.The training and continuing education of all

streams of health care professionals involved in themanagement of oral cancer should be enhanced.Excellent clinicians capable of leading such initiativesare employed in many centres in India today.

Pain control and palliative care

Oral cancer causes severe physical, psychosocial andspiritual pain to patients and their families. Trained


Gupta et al.

staff and facilities for caring for terminally ill patientsand their families are required across the nation63,69:many such already exist, provided by government andby non-government organisations, but their availabil-ity is patchy.

Data storage and documentation

At present, cancer registration in India is voluntary.The ICMR network of cancer registries is doing excel-lent work, but this should be expanded to ensuregreater population coverage: for example, no registriesexist in the populous and relatively poor states of Ut-tar Pradesh, Bihar and Orissa. Legislative support formandatory registration is required, along with anincrease in resources to permit not only the morecomplete capture of cases, but to assist with follow-up.Currently, there is no system of registries in India

for recording cases of OPMD. We strongly recom-mend that such a system be established across thenation. Given that India has well over 200 dental col-leges, most of which have dedicated oral pathologistsand oral physicians, this should be possible. The IA-OMP has expressed interest in coordinating such aninitiative73. A major task of such registries would beto document the malignant transformation rates ofthe various OPMDs and to identify the factors thathave predictive value for this. These tasks should becombined with public health promotion, diagnosticand management responsibilities, and with the localactivities of Indian Dental Association S.P.O.T. clinicsin the private sector.

CONCLUSIONS

Oral cancer is a multidimensional problem that hasimmense impact on individuals and their families, onall health services and on wider society74. We recom-mend the adoption of a diagonal approach to treat-ment and prevention that is fully integrated intoprimary care and into the existing activities of themany relevant medical, religious and social organisa-tions63. This approach must be developed in synergywith global leadership organisations such as theWHO, the IARC, the Union for International CancerControl, the International Federation of Head andNeck Oncologic Societies, the International Academyof Oral Oncology, the FDI World Dental Federation,the International Association for Dental Research,and the growing number of bodies dedicated to globalhealth and the management of NCDs. In addition, weneed to re-orient oral health research, practice andpolicy towards a model based on social determinantsand support closer collaboration between, and inte-gration of, dental and general health research7.

To summarise, efforts towards the control of oral can-cer in India will benefit from an approach based on com-mon risk factors that integrates oral health with overallhealth care and applies existing knowledge in a whole-society approach. Ever-present funding constraints andlack of political will in the field of health care must bechallenged by continued and innovative advocacy.

Acknowledgement

We are grateful to all our colleagues in India for theircollaboration over many years.

Conflicts of interest

None declared.

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Correspondence to:Professor Newell W. Johnson,

Emeritus Professor of Oral Health Sciences,King’s College London

Professor of Dental Research,Griffith Health Institute,

Griffith University, Gold Coast Campus,Building GO5, Room 3.22A, Gold Coast,

Queensland 4222, Australia.Email: [email protected]



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