1 oral cancer: epidemiology, risk factors and prevention. carlo la vecchia
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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.