Epidemiology of oral cancer

Epidemiology, Etiology and Prevention of Oral Cancer

1. EPIDEMIOLOGY OF ORAL CANCER Dr. Nabeela Basha Seminar 11 2

2. Contents Introduction Global Scenario of Oral Cancer Spectrum of Oral Cancer in India Epidemiological studies Aetiology and Risk Factors Staging of Oral Cancer Prevention of Oral Cancer Cancer Registration in India Conclusion Previous year questions References 3

3. Introduction Cancer: WHO defines it as the uncontrolled growth and spread of cells. Growths often invade surrounding tissue and can metastasize to distant sites. Can be prevented by avoiding exposure to common risk factors, such as tobacco smoke . Significant proportion of cancers can be cured, by surgery, radiotherapy or chemotherapy . 4

4. Oral Cancer The term oral cancer is used to describe any malignancy that arises from oral tissues. One of the most common sites of oral cancer is on lateral aspect of the tongue. In the International Classification Of Diseases, oral cancer is classified under the rubrics 140 (lip), 141 (tongue), 143 (gingiva), 144 (floor of the mouth) and 145 (other parts of the mouth). Oral Cancer Foundation 2016 5

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6. Global Scenario of Oral Cancer World Health Report 2004 describes cancer as accounting for 7.1 million deaths in 2003, and it was estimated that the overall number of new cases will rise by 50% in the next 20 years. Oral Cancer is the 8 th most common cancer worldwide, the prevalence of which is particularly high among men . In South-central Asia – Oral Cancer ranks the 3 rd most common type of cancer . 7

7. Between the 1960s and the present, male patients aged 30-39 years have presented a nearly fourfold increase in oral cancer incidence. Prevalence of tongue cancer is noted in parts of Europe showing male incidence rates up to 8.0 per 100,000 per annum. High male lip cancer rates are reported for regions of North America ( 12.7 per 100,000 per annum), Europe ( 12.0 per 100,000 per annum) and Oceania ( 13.5 per 100,000 per annum). 8

8. Spectrum of Oral Cancer in India The Indian subcontinent, especially India itself because of its large population, has long been regarded as the global epicenter of oral cancer. With an annual incidence rate of 64,460 in India, it is estimated that among the 400 million individuals aged 15 years and over, 47% use tobacco in one form or the other. As cancer registration is not Compulsory in India, it is probable that the true incidence and mortality are much higher: many cases go unrecorded and/or are lost to follow-up. 9

9. Epidemiological Studies Gupta et al conducted a systematic review of oral cancer registries in India in 2013 to enumerate the present epidemiological picture of oral cancer in India. According to the review, Oral cancer with ICD-10 codes ranging C01-C06, ranks amongst the 3 most common cancers in India. This systematic review shows, in India, approximately 70,000 new cases and more than 48,000 oral cancer-related deaths occur yearly. 10

10. The overall incidence as high as 19 per 100,000 per annum has been derived from Indian databases. 11

11. Byakodi R et al conducted a study in 2012 in Sangli , Maharashtra and found that the prevalence of oral cancer was 1.12%. The findings in the study revealed a high prevalence of oral cancer and a rampant misuse of variety of addictive substances in the community. 12

12. Coelho K. R conducted a systematic review in 2012 on oral cancer prevalence in India. The study found out that oral cancer was a major problem in the Indian subcontinent where it ranks among the top 3 types of cancer in the country. Age-adjusted rates of oral cancer was high , i.e., 20 per 100,000 population which accounts for over 30% of all cancers in the country. 13

13. Oral cancer is an important public health issue. During Social engineering phase (1960-1980)- pattern of disease changed in developed world , new health problems in form of chronic diseases began to emerge, e.g., cancer , diabetes, cardiovascular diseases, alcoholism and drug addiction etc. A new concept, the concept of "risk factors" as determinants of these diseases came into existence. Epidemiology of Oral Cancer 14

14. Non-communicable diseases (NCDs) are a major threat to development, economic growth and human health . There is variation in incidence and pattern of the disease which can be attributed to the combined effect of ageing of the population, as well as regional differences in the prevalence of disease-specific risk factors. The major risk factor leading to oral cancer is tobacco . World Economic Forum and the Harvard School of Public Health(November 2014) 15

15. Incidence and Prevalence of Oral Cancer The high incidence of oral cancer in India has long been linked with the habit of betel quid chewing, tobacco consumption, smoking and indigenous methods of oral habits. 16

16. Global Youth Tobacco Survey (GYTS) India (Ages 13-15) The India GYTS includes data on prevalence of cigarette and other tobacco use as well as information on five determinants of tobacco use: access/availability and price, exposure to secondhand smoke (SHS), cessation, media and advertising, and school curriculum. The India GYTS was a school-based survey of students in grades 8, 9 and 10 conducted in 2009. A total of 10,112 students aged 13-15 years had participated. 17

17. 14.6% of students used any one form of tobacco; 4.4% smoked cigarettes; 12.5% used some other form of tobacco. SHS exposure was moderate – one in five students lived in homes where others smoked, and more than one-third of the students were exposed to smoke around others outside of the home; one-quarter of the students had at least one parent who smoked. Two-thirds of the students thought smoke from others was harmful to them. 18

18. Over 6 in 10 students thought smoking in public places should be banned. Two-thirds of the current smokers wanted to stop smoking. Three-quarters of the students had seen anti-smoking media messages in the past 30 days. 19

19. Global Adult Tobacco Survey (GATS-2) India (2016-17) GATS 2016-17 was conducted by the Union health ministry with technical assistance from the World Health Organisation (WHO) and Centres for Disease Control and Prevention (CDC), US. A nationally representative household survey of persons aged 15 and above, it was conducted in all 30 states of India and two union territories. A total of 74,037 individuals were interviewed between August 2016 and February 2017. 20

20. India has witnessed an overall decline in the number of tobacco users in past seven years, especially among the age group of 15 to 24. As per the report, over 61.9 per cent adults thought of quitting cigarettes, 53.8 per cent thought of quitting bidi and 46.2 per cent adults thought of quitting smokeless tobacco because of the warnings on tobacco products. 21

21. While the number of tobacco users has reduced by about 81 lakh in last seven year, tobacco products have also gradually become unaffordable. The average expenditure incurred on last purchase of cigarette, bidi and smokeless tobacco is Rs 30, Rs 12.5 and Rs 12.8 respectively. The expenditure on cigarette has tripled and that on bidi and smokeless tobacco has doubled since GATS 1, the survey found. 22

22. EPIDEMIOLOGICAL TRIAD 23

23. Host Factors Human host- “soil” and Disease agent- “seed” Classified as: Demographic characteristics- Gender :  Oral cancer and oropharyngeal cancer are twice as common in men as in women. This difference may be related to the use of alcohol and tobacco, a major oral cancer risk factor that is seen more commonly in men than women.  24

24. Mishra et al (2014) 25

25. Age: Disease that occurs mainly in the elderly . Most of the cases of OC occur between 50 and 70 years of age , it still could occur in children as early as 10 years of age in the absence of any known risk factors. Mean age of occurrence of cancer in different parts of oral cavity is usually between 51-55 years in most of the countries but higher around 64 years. 26

26. Race: An elevated incidence of cancers of the nasopharynx has been reported in persons of Chinese ancestry in the United States and elsewhere ; decreased incidence of oral cancers has been observed in American Native populations compared with American whites. http://www.oralcancerfoundation.org/cdc/cdc_chapter1 27

27. Biological characteristics Genetic: Increased risk of oral cancer associated with exposure to genetic mutagens in tobacco, alcohol and betel quid. Gene mutations- 3p, 4q, 6p, 8p, 9p, 11q, 13q (retinoblastoma [Rb] tumor suppressor gene), 14q, 17p (p53 tumor suppressor gene), 18q (deleted in colon cancer [DCC] tumor suppressor gene) and 21q.1113 28

28. Social and economic characteristics Socio economic status : oral cancer affects those from the lower socioeconomic groups of society due to a higher exposure to risk factors such as the use of tobacco. Ken Russell Coelho ( 2012) 29

29. Education: Illiterates those who never attended school and with low educational attainment have greater risk. In the Indian population OR for OC related to education is greater for illiterates (6.4) compared to low education level (5.3). Krishna Rao et al (2014) 30

30. Occupation: Certain occupations where exposure to carcinogens is common like tar manufacturing. Certain oils, textile industries etc – are susceptible to cancer. Leather workers are shown to have a higher rate of cancer of buccal cavity. Other workers at increased risk for cancer: Coal mine and tar workers, Oil factory workers, Uranium miners and X-ray technicians. 31

31. BLOOD GROUPS: Association of blood groups with oral cancer has also been observed. It has been reported that Group O showed the least susceptibility, Group B and AB showed doubtful susceptibility and Blood Group A showed higher susceptibility. 32

32. Lifestyle factors Living habits and Nutrition : It has been observed that vitamin deficiencies (A, C, E)- contribute to high prevalence of oral cancers in India. In rural India- oral pre-cancerous lesions associated with low plasma levels of vitamin E and beta-carotene. Body mass index (BMI) has been inversely associated with oral cancer, and paan chewers with low BMI has a very high risk of oral cancer.

33. LINKS BETWEEN CANCER AND DIETARY FACTORS 34

34. Site distribution Lip cancer is most common in fair skinned races, particularly in rural areas and in men who work out doors. Intra oral cancer in western countries most commonly affects the lateral borders of the tongue. Buccal mucosa (65%), lower alveolus (30%) and retromolar trigone (5%) : these constitute more than 60% of all cancers.

35. Agent factors The disease "agent" is defined as a substance living or non-living, or a force, tangible or intangible, the excessive presence or relative lack of which may initiate or perpetuate a disease process. Biological factors: Human papilloma viruses , or HPV, is a risk factor for oral and oropharyngeal cancers. In particular, there is a strong link between HPV-16 and oropharyngeal cancer. 36

36. Chemical: Habit of applying dry lime and ‘ kaththa ’ (Acacia katechu ) on superficial mucosal lesion/ abrasion for healing is a common practice in north central India. In 1984 Bhopal Gas Tragedy, the local population exposed to high levels of methyl isocynate showed a marginally increased risk for cancer of oropharynx suggesting it to be a potential established risk factor. 37

37. Mechanical- An association between oral carcinoma and chronic irritation of the mucosa by the dentures . Case reports have detailed the development of oral carcinomas in patients who wear ill fitting dentures . Shafers (2012) 38

38. Environment factors (extrinsic) Ultraviolet (UV) radiation, and in particular solar radiation , is carcinogenic to humans, causing all major types of skin cancer, such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma .  The lower lip receives considerable sunlight exposure than upper lip that is comparatively shaded accounting for a higher occurrence than later. http://www.who.int/cancer/prevention/en/ 39

39. Indian race with a tanning skin and a higher melanin content naturally protects against the ultraviolet induced actinic skin changes, hence majority of the population (farmers and labourers) working outdoor in the scorching sunlight is less effected 40

40. Major risk factors for Oral cancer 41

41. TOBACCO 42

42. SMOKING TOBACCO 43

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44. 45 SMOKELESS TOBACCO

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47. CONSTITUENTS IN TOBACCO CONSTITUENTS ADVERSE EFFECTS Polycyclic aromatic hydrocarbon Carcinogenesis Nicotine Carcinogenic Phenol Ganglionic stimulation and depression & tumour promotion Benzopyrene Tumour promotion & irritation CO Impaired O 2 transport and repair Formaldehyde and oxides of N 2 Toxicity to cilia and irritation Nitrosamine Carcinogenic 48

48. Reverse smoking : The habit of tobacco smoking with the lighted end inside the mouth (reverse smoking) is found in people of the lower socio-economic states in Colombia, Panama. Pipe Smoking : A high incidence of lip cancer has been observed in those who smoke with short-stemmed pipes. 49

49. Major risk factors for Oral cancer 50

50. A synergistic effect of tobacco and alcohol has been observed. Account for 75% of all oral and pharyngeal cancers and have been implicated in the formation of multiple primary cancer sites found in oropharyngeal patients. http://www.who.int/cancer/prevention/en / 51

51. Alcohol may promote carcinogenesis by include dehydrating effects of alcohol on the mucosa increasing mucosal permeability and effects of carcinogen in tobacco, nutritional deficiency and solubilizing tobacco. Attributable fractions vary between men and women for certain types of alcohol-related cancer, mainly because of differences in average levels of consumption. 52

52. For example, 22% of mouth and oropharynx cancers in men are attributable to alcohol whereas in women the attributable burden drops to 9%. http://www.who.int/cancer/prevention/en/ 53

53. Histological Classification of Cancer and Precancer of the Oral Mucosa 1. Carcinomas • Squamous cell • Verrucous • Basaloid squamous cell • Adenoid squamous cell • Spindle cell 54

54. 2 . Benign lesions capable of microscopically resembling oral squamous cell carcinoma and oral verrucous carcinoma • Papillary hyperplasia • Granular cell tumour • Discoid lupus erythematosus • Median rhomboid glossitis • Keratoacanthoma • Necrotizing sialometaplasia • Chronic hyperplastic candidiasis • Verruca vulgaris 55

55. 3. Precancerous lesions ( clinical classification) • Leukoplakia • Erythroplakia • Palatal keratosis associated with reverse smoking 56

56. 4 . Benign lesions capable of resembling oral precancerous lesions • White lesions resembling leukoplakia • Red lesions resembling erythroplakia • Focal epithelial hyperplasia • Reactive and regenerative atypia 57

57. 5. Precancerous conditions • Sideropenic dysphagia • Lichen planus • Oral submucous fibrosis • Syphilis • Discoid lupus erythematosus • Xeroderma pigmentosum • Epidermolysis bullosa 58

58. Precancerous oral lesions India accounts for one third of the world’s oral cancer and has a high rate of pre-malignant lesions. The World Health Organization classifies oral precancerous/ potentially malignant disorders into 2 general groups, as follows. 59

59. A precancerous lesion is “a morphologically altered tissue in which oral cancer is more likely to occur than its apparently normal counterpart.” The precancerous lesions include leukoplakia, erythroplakia , and the palatal lesions of reverse smokers. • A precancerous condition is “a generalized state associated with significantly increased risk of cancer.” The precancerous conditions include submucous fibrosis, lichen planus, epidermolysis bullosa, and discoid lupus erythematosus. 60

60. Leukoplakia is the most common premalignant oral lesion. Leukoplakia is described as a white patch which cannot be rubbed off and cannot be diagnosed as another specific disease entity. It is commonly seen on buccal mucosa, gingiva and tongue. Leukoplakia prevalence in India varies from 0.2%-5.2%, the overall prevalence of precancerous lesion among patients attending hospital in certain places of India range between 2.5% to 8.4% 61

61. Oral premalignant lesions have shown a rate of progression to cancer up to 17% within a mean period of 7 years after diagnosis. In India a cohort study conducted in Ernakulum district of Kerala showed 79% of cancers arose from preexisting precancerous lesions and conditions. 62

62. Prevalence of Oral precancerous lesions/conditions Lesion/Condition % Studies conducted by Oral Leukoplakia 0.3 – 11.7 Yardimci G et al, Shulman et al, Kumar A et al Oral Erythroplakia 0.02 – 3.84 Yardimci G et al, Gaphor SM et al, Narasannavar A et al Oral Lichen Planus 0.5 - 3.0 Yardimci G et al, Narasannavar A et al Oral Submucous Fibrosis 0.2 – 1.2 de Souza et al 63

63. Clinical Presentations of Cancer of Oral Mucosa More than 90% of oral cancers are Squamous cell carcinomas. The other 10% are salivary gland tumours, lymphoma, sarcoma and others. A considerable amount of clinical uncertainty is involved in the early detection of malignancy as many of the lesions may not always remain benign. However, following clinical signs should be regarded with great suspicion. 64

64. ULCER INDURATION FUNGATION/GROWTH FIXATION FAILURE TO HEAL OF A TOOTH SOCKET OR ANY OTHER WOUND TOOTH MOBILITY, PAIN/PARESTHESIA, DYSPHAGIA WHITE/RED PATCHES LYMPHADENOPATHY 65

65. 66 TNM STAGING AND GRADING Devoloped by PIERRE DENOIX in France between 1943 and 1952. Staging: extend of spread of tumor with in the patient Grading: microscopic and macroscopic degree of differentiation of the tumor.

66. 67 Grading and staging are two systems to determine the prognosis and choice of treatment after malignant tumor detected. “Tumor – Node – Metastasis” Or “TNM” staging system” T = Size of primary tumor in centimeters N = Involvement of local lymph nodes M = Distant metastasis.

67. TNM staging American joint committee on cancer 1997 68

68. 69 CANCER REGISTRATION IN INDIA Until 1964, no information on cancer occurrence in India was available from surveys. However, the boost for cancer registration in India was in 1982, through initiation of National Cancer Registry Program (NCRP) by Indian Council of Medical Research.

69. 70 PREVENTION OF ORAL CANCER Mainly focuses on modifying habits associated with the use of tobacco. India- 4th largest consumer and 3rd largest producer of tobacco. 3 well-known approaches: Regulatory Approach Service Approach Educational Approach

70. 71 REGULATORY OR LEGAL APPROACH As early as 1590, The Government in Japan, edict against tobacco use, where users were penalized by having their property confiscated or were jailed. Similar edicts have been reported in Turkey, Russia and China. Religious groups have also banned the use of tobacco.

71. 72 In India, Cigarette Act 1975 has made it necessary to print warning on cigarette packets. Bidi, not being included for printing statutory warnings. In some countries like Italy, Norway, Portugal Singapore and Thailand there has been a ban on advertising tobacco products.

72. 73 The cigarette packs are now required to carry graphical health warnings. After years of wrangling, graphic health warnings (GHW) are now mandatory on tobacco products sold in India. The Cigarette and Other Tobacco Products (Packaging and Labelling) Rules 2009 requiring GHW came into force on 31 May.

73. 74 Cigarettes And Other Tobacco Products (prohibition Of Advertisement And Regulation Of Trade And Commerce, production, Supply Distribution) Act (COTPA) , in 2003: The Indian Parliament passed the bill in April 2003. This bill became an act on 18 May 2003. The key provisions of COTPA-2003 are as follows:

74. 75 a. Prohibition Of Smoking In Public Places Implemented From 2nd October 2008. b. Prohibition Of Advertisement-direct Or Indirect And Promotion Of Tobacco Products. c. Prohibition of sales to minors(tobacco products cannot be sold to children less than 18yrs of age and cannot be sold within a radius of 100 yards of any educational institutions.

75. 76 d. Regulation of health warning in tobacco products pack . English and one more Indian language to be used for health warnings on tobacco packs . Pictorial health warnings also to be included. e. Regulations and testing of tar and nicotine content of tobacco products and declaring on tobacco product packages. f. Law pertaining to pictorial health warnings on tobacco product packages: Implemented with effect from 31st May 2009.

76. 77 SERVICE APPROACH Primary goal is a fundamental of prevention. This can be achieved through screening and early detection. It also provides an opportunity to identify and council the patients about habits that increase the risk of cancer. Other than professional, primary health care workers can also be used for screening. Diagnostic methods such as Biopsy Technique, Exfoliative Cytology, Toluidine Blue Vital Staining can be used under this approach.

77. 78 EDUCATIONAL APPROACH The process of becoming a smoker, for example, essentially involves four stages : Awareness Initiation / Experimentation Habituation Maintenance / Dependence So education has an important part to play in discouraging people from starting its use and from helping people to stop the habit.

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79. 80 Guide to Counseling for tobacco cessation (5A’s): Ask – use of tobacco Advise – non users to never use and users to quit Assess- the patient readiness to quit Assist- with quitting Arrange- for follow ups

80. 81 Counseling those unwilling to quit (5Rs):

81. 82 USE OF PHARMACOTHERAPY There are 2 main types of pharmacotherapy for tobacco use cessation: Nicotine Replacement therapies (NRT): These lessen the cravings and other withdrawal symptoms and the individual learns to stop the behaviours connected with tobacco use. Eventually, patients need to give up using nicotine replacement. Antidepressants: They also serve as anticraving medications and can be used with NRTs.

82. Conclusion India is a heterogeneous country, and solutions to the challenge of oral cancer must be tailored. A comprehensive set of solutions must be deployed by multiple stakeholders to put India on the path to further preventing and controlling this disease. 83

83. Affordable and accessible diagnostic, therapeutic and palliative care services should be made available in India. Tobacco control has to be strengthened and the present status of women and children as non-users of tobacco should be sustained at any cost. 84

84. Previous Year Questions Smokeless tobacco and oral cancer [RGUHS M.D.S. Degree Examination – April/May 2007; 10 marks]. Diet and oral cancer [RGUHS M.D.S. Degree Examination – April/May 2007; 10 marks]. Prevention of oral cancer. [RGUHS M.D.S. Degree Examination – May 2011; 10 marks]. Discuss the role of tobacco in oral health [RGUHS M.D.S. Degree Examination – May 2013; 20 marks]. Tobacco control [RGUHS M.D.S. Degree Examination – May 2014; 10 marks]. 85

85. References K. Park. Park’s Textbook of Preventive and Social medicine. 23th ed. Jabalpur: M/s Banarsidas bhanot ; 2015. MC Gupta and BK Mahajan. Textbook of Preventive and Social Medicine. 3rd Edition 2003. Jaypee Brothers Medical Publishers Ltd, New Delhi. P. Soben . Essentials of preventive and social medicine. 5th ed. Arya publishing house, New Delhi; 2013. Hiremath SS. Textbook of Preventive and Community Dentistry. 3rd edition. Elsevier Publishers, New Delhi; 2016. 86

86. CM Marya . A Textbook of Public Health Dentistry. 1st Edition 2011. Jaypee Brothers Medical Publishers, New Delhi. Byakodi R,Byakodi S,Hiremath S,Byakodi J,Adaki S,Mara.the K et al.Oral Cancer in India:An Epidemiological and Clinical Review.J Community Health 2012;37:316-319. Centre for Disease Control.Improving Diagnoses of Oral Cancer. http://www.cdc.gov/OralHealth/pdfs/oral_cancer.pdf CoelhoKR . Challenges of the Oral Cancer Burden in India. Journal of Cancer Epidemiology: 2012, June :1-17. 87

87. American joint committee on cancer 1997. Cancer: Current scenario, intervention strategies and projections for 2015 M. Krishnan Nair, Cherian Varghese, R. Swaminathan NCMH Background Papers Burden of Disease in India, WHO India. Ken Russell Coelho, Review Article Challenges of the Oral Cancer Burden in India Journal of Cancer Epidemiology Volume 2012, 17 pages Krishna Rao et.al Epidemiology of Oral Cancer in Asia in the Past Decade- An Update (2000-2012) Asian Pac J Cancer Prev , 14 (10), 5567-5577 88

88. Shafer’s Textbook of Oral Pathology,2012 Seventh Edition NCRP ANNUAL REPORT of hospital based cancer registries 2007- 2011. Petti S Lifestyle risk factors for oral cancer,Oral Oncology. 2009 Apr-May;45(4-5):340-50. WHO (ONLINE)http://www.who.int/cancer/prevention/en/ WHO Report on the Global Tobacco Epidemic, 2015. http://www.icd10data.com/ICD10CM/Codes/C00-D49/C00-C14 89