1. 1 ORAL CANCER: EPIDEMIOLOGY, RISK FACTORS AND PREVENTION. Carlo La Vecchia

2. 2 Overview of the descriptive epidemiology of oral cancer, and the best recognized risk factors, with specific focus on perspectives for prevention.

3. 3 Oral cancer incidence and mortality rates vary widely across the world, and the highest rates are registered in a few developing countries, including India, Pakistan and Bangladesh, where this is the most common form of cancer, and also in Hong Kong.

4. 4 Oral cancer incidence

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6. 6 To provide a comprehensive picture of oral cancer in Europe, we obtained from the WHO database official death certification data for 32 European countries from 1950 onwards, and the corresponding estimates of the resident population.

7. 7 Oral cancer mortality in Europe

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9. 9 Parameter estimates for age, period and cohort effects were derived from a log- linear Poisson model with arbitrary constraints on the parameters for selected countries.

10. 10 Estimates of age, cohort of birth and period of death effects for oral cancer mortality in selected European countries, derived from a log-linear age, period and cohort model. Modified from La Vecchia et al., 1998

11. 11 Estimates of age, cohort of birth and period of death effects for oral cancer mortality in selected European countries, derived from a log-linear age, period and cohort model. Modified from La Vecchia et al., 1998

12. 12 Strong cohort effects were observed, with moderate declines in cohorts born before 1920, and strong increases thereafter. The rise in most recent cohorts was particularly large in Hungary, former Czechoslovakia and Germany; in the United Kingdom, declines were observed in older cohorts, followed by a moderate increase afterwards.

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14. 14 No major or systematic trend in oral cancer mortality, was observed in the United States, whose overall age- standardized rates declined from 4.7 in 1955-59 to 2.7/100,000 males in 2000, and remained around 1.0/100,000 females.

15. 15 Oral cancer showed no clear change in other American and Asian countries whose mortality data are available, except Japan, whose rates increased in males, but remained comparatively low, i.e. around 2/100,000 males and 0.6/100,000 females.

16. 16 No major improvements in oral cancer prognosis have been achieved in the last decades. Thus, differences in mortality between time periods and geographic areas should be interpreted essentially in terms of changes in risk factor exposures.

17. 17 Alcohol interacts with tobacco smoking in the development of cancers of the oral cavity and pharynx. How elevated alcohol consumption results in increased risk is however still unclear.

18. 18 Data have been derived from a case- control study conducted in a high risk area from northern Italy, including 749 cases and 1,775 controls with acute, nonneoplastic diseases, unrelated to alcohol and tobacco consumption.

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20. 20 Type of alcohol All types of alcoholic beverages contribute to cancer risk in proportion to their alcoholic content.

21. 21 Type of alcohol The most frequently used alcoholic beverage in each population tends to emerge as the most important determinant of oral cancer. In fact, heavy drinkers who avoid the consumption of the locally most common (and generally cheapest) alcoholic beverages are rare.

22. 22 Alcohol in nonsmokers Alcohol-related risk of oral and pharyngeal cancers in nonsmokers. There was a trend toward increasing risk with increasing alcohol consumption.

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24. 24 Tobacco Very few oral cancer patients describe themselves as non-smokers. ORs for current smokers, after allowance for alcohol and other covariates of interest, were 11.1 for oral cavity and 12.9 for pharyngeal cancer.

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26. 26 Stopping smoking The risk associated with pipe and cigars indicates a strong effect. A decreased risk for longer time since stopping smoking indicates that cancer risk among` ex-smokers substantially declines after cessation of smoking, to approach that of never smokers after 20 years or more.

27. 27 Oral cancer – stopping smoking (La Vecchia et al., 1999)

28. 28 Alcohol and tobacco interaction The OR for the highest levels of alcohol and tobacco was increased 80-fold relative to the lowest levels of both factors. The joint effect of smoking and drinking appears, therefore, greater than multiplicative.

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30. 30 Franceschi et al., 1999 Alcohol and tobacco interaction

31. 31 Alcohol and tobacco interaction In this dataset, the interaction accounted for 40 to 75% of the excess risk due to alcohol and tobacco.

32. 32 (Bosetti et al., 2000) Oral cancer in women

33. 33 Oral cancer in women

34. 34 Diet An association between diet and oral cancer has long been suggested. Iron deficiency and primary sideropenic anaemia, since their first descriptions early this century, have been associated with malignancies of the oral cavity.

35. 35 Diet After allowance for tobacco, alcohol and social class, associations were found with consumption of pasta or rice, polenta, cheese, eggs and pulses, with ORs of the order of 1.4-1.9 for the highest versus the lowest intake tertile.

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37. 37 Diet Frequent consumption of fruit and vegetables, including carrots, fresh tomatoes and green peppers, was associated with reduced risk of oral and pharyngeal cancer, with ORs of the order of 0.5-0.7 for the highest versus the lowest tertile. Favourable role of olive oil/unsaturated fats.

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39. 39 Franceschi et al., 1999

40. 40 Micronutrients Decreased risks with increasing consumption of vitamins A and C, fresh fruit, green leaf and other vegetables. The largest study available - a population-based case-control investigation conducted in the United States - indicated a specific protection by fresh fruit, which was not explained by beta-carotene, vitamin C or fibre content of fruit and vegetables (McLaughlin et al., 1988).

41. 41 Micronutrients As in American data, beta-carotene, but not retinol, was inversely related with risk of cancers of the oral cavity and pharynx, but the association was not stronger than that with measures of fruit consumption (OR for the upper level=0.3).

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43. 43 Negri et al., 2000 Micronutrients

44. 44 Pelucchi et al., 2003 Folate & alcohol

45. 45 Diet – Attributable risk Whereas measures against smoking and heavy alcohol drinking remain of high priority, approximatively 15% or oral and pharyngeal cancers can be attributed to dietary deficiencies (or unbalances), which may correspond to 5,000 deaths per year in Europe.

46. 46 Chemoprevention Chemoprevention trials, suggest that both vitamin A (retinoids) and its precursors carotenoids have some activity in reducing dysplastic lesions in the oral mucosa (micronucleated exfoliated cells and leukoplakia). This evidence is too preliminary to find clinical application outside controlled trials. The predictive value of leukoplakia on subsequent oral cancer risk remains, moreover, still unclear.

47. 47 Human papillomavirus At least 11 studies compared HPV DNA presence in cases of cancer of the oral cavity and corresponding controls. Most studies found higher HPV positivity among cases (overall: 106/552, 19%) than controls (overall: 32/545, 6%).

48. 48 Herrero et al., 2003 HPV

49. 49 HPV Epidemiological and experimental evidence lends some support to the possibility of HPV playing an aetiological role in the onset of oral cancer.

50. 50 Oral hygiene/social class Oral hygiene and dentition may have had some role. These are, however, largely a surrogate of social class. Mouthwash and smokeless tobacco have a minor role, if any, on oral cancer incidence in Europe.

51. 51 Screening for oral cancer Six Asian screening programs included from about 17,000 to over 100,000 individuals, with coverage of the target population between 7% and 78%. The proportion of individuals with suspicious oral lesions ranged between 1.3% and 16.3%. Each program led to the identification of several oral cancers.

52. 52 Screening for oral cancer

53. 53 If advanced oral cancer has to become the exception instead of the rule, transition probabilities and sojourn time of various oral lesions up to malignancy should be known better. For this purpose, all available evidence, accumulated from previous screening programs and follow-up-studies of preneoplastic lesions (e.g., chemoprevention studies), should be considered. Only, then, it will be possible to assign the right priority to oral cancer screening. Screening for oral cancer

54. 54 Conclusions 1 In the whole of Italy, alcohol, tobacco and diet account for over 80% of oral and pharyngeal cancers, and could, in principle, reduce the burden of the disease from 2,400 deaths to about 200 for males, and from 500 to 200 for females, thus also explaining the difference in rates between the two sexes.

55. 55 Conclusions 2 Oral cancer is therefore a largely preventable disease in developed countries. A consensus conference, concluded that, is no evidence to support population screening for oral cancer, and it is difficult even to recommended the need for randomised trials.