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ORAL CANCER: EPIDEMIOLOGY, RISK

FACTORS AND PREVENTION.

Carlo La Vecchia

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Overview of the descriptive epidemiology of oral cancer, and the best recognized risk factors,

with specific focus on perspectives for prevention.

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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.

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Oral cancer incidence

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Oral cancer incidence

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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.

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Oral cancer mortality in

Europe

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Oral cancer mortality in

Europe

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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.

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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

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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

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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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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.

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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.

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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.

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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.

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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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Type of alcohol

All types of alcoholic beverages contribute to cancer risk in

proportion to their alcoholic content.

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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.

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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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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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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.

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Oral cancer – stopping smoking

(La Vecchia et al., 1999)

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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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30Franceschi et al., 1999

Alcohol and tobacco interaction

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Alcohol and tobacco interaction

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

tobacco.

32(Bosetti et al., 2000)

Oral cancer in women

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Oral cancer in women

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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.

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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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DietFrequent 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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Franceschi et al., 1999

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MicronutrientsDecreased 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).

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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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Negri et al., 2000

Micronutrients

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Pelucchi et al., 2003

Folate & alcohol

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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.

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ChemopreventionChemoprevention 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.  

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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%).

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Herrero et al., 2003

HPV

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HPV

Epidemiological and experimental evidence lends some support to the

possibility of HPV playing an aetiological role in the onset of oral

cancer.

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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.

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Screening for oral cancerSix 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. 

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Screening for oral cancer

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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

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Conclusions 1In 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.

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Conclusions 2Oral 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.