Etiology

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Tobacco smoking and alcohol

The dominant risk factors are tobacco use and alcohol abuse, which are strongly synergistic {228}. Alcohol and tobacco account for 75% of the disease burden of oral and oropharyngeal malignancies in Europe, the Americas and Japan {227,1862}. For the highest levels of consumption compared to the lowest ones relative risks from 70 to over 100 have been shown {287,1811}. Relative risks in case-control studies showing a supermultiplicative effect in the oral cavity, between additive and multiplicative in the oesophagus, and multiplicative in the larynx, reflecting degree of contact with both these agents at these sites {797}. Most of the rise in western countries in recent years has been attributed to rising alcohol consumption in northern Europe {1597 and rises in tobacco consumption in parts of southern Europe. Significant risk increases have also been reported amongst non-drinking smokers and, to a lesser extent, non-smoking heavy m? im M

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Fig. 4.4 Trends in mortality from cancer of the oral cavity and pharynx in some European countries. The large differences observed (currrently 10-fold in between Hungary and Finland) largely reflect past success and failure in tobacco and alcohol control. From F. Levi et al. {1483}.

drinkers {1406}. Studies that have attempted to estimate a difference between wine, beer and hard liquors generally indicate that heavy consumption of all types of alcoholic beverage confers risk, the differences in risk estimates being largely due to socio-cultural correlates of drinking patterns in various populations {142,1404}.

Ultraviolet light and contact with smoking appliances are important for lip vermillion.

Tobacco chewing

Oral smokeless tobacco is a major cause of oral {969} and oropharyngeal {2908} squamous cell carcinoma in the Indian subcontinent, parts of South-East Asia, China and Taiwan and in emigrant communities therefrom, especially when consumed in betel quids containing areca nut and calcium hydroxide (lime). Areca nut has been declared a known human carcinogen by an IARC Expert Group (2003). In India chewing accounts for nearly 50% of cancers of the oral cavity and oropharynx in men and over 90% in women {108}. Traditional tobacco products used in Sudan and the Middle East, which are powdered and fermented and mixed with sodium bicarbonate, contain very high levels of tobacco-specific nitrosamines and are highly carcinogenic {1171}. Those forms of non-flue cured smokeless tobacco used as oral snuff in Scandinavia and North America is less carcinogenic {1230} - though they cause nicotine addiction.

Human papillomavirus (HPV) infection

HPVs, especially those genotypes of known high oncogenic potential in uterine cervix and skin such as HPV 16 and 18, are found in a variable but small proportion of oral, and up to 50% of tonsillar and oropharyngeal SCCs, especially the tonsil. Recent studies suggest that HPV may be responsible for a small fraction of oral, and up to 40% of oropharyngeal, cancers {888,1077}. This has lead to speculation that HPV infection, perhaps arising from oral/genital contact, might be important in some cases {2284}. Of interest is the observation that HPV-containing cancers at these sites do not generally show TP53 mutations, contrary to HPV DNA-negative cancers {660,1077}. It is well known that HPV 16 E6 protein inactivates p53 protein, suggesting that HPV and smoking might operate, in part, on the same criti

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