Some of the major risk factors of oral and oropharyngeal cancer include various types of tobacco consumption such as smoking and smokeless, alcohol consumption, areca nut chewing, poor nutrition, genetic factors, virus infections and chronic trauma.
The main causes of oral cancer around the world are various types of tobacco, alcohol consumption and also the increasing number of HPV infections. Although the relative contribution of risk factors differs among populations, oral cancer is predominantly a disease of the poor. And so, fundamental changes in socio-economic status and measures to reduce production, demand, marketing, and tobacco products and alcohol use can prevent this devastating disease1. A healthy diet, good oral and awareness of the signs and symptoms of the disease are also important.
Smokeless and Smoking Tobacco Use
Smokeless tobacco betel quid, snuff, and betel nut alternatives such as gutkha, nas, khaini, naswar, mishri, mawa and gudakhu) increase the risk of oral cancer and precancerous lesions by 2 to 15 times. In most regions, betel quid consists of betel nut, tobacco, catechu, slaked lime, and also many spices wrapped in betel nut.
As a result consistent evidence from multiple studies suggests that all forms of tobacco smoking increase the risk of oral cancer in men and women by 2 to 10-fold2. The risk increases significantly with the duration and frequency of tobacco use. The risk for former smokers is consistently lower than for current smokers, and the risk decreases with increasing years after quitting. Consumption of smokeless tobacco products and alcohol along with smoking significantly increases the risk of oral cancer. The biological potential is conferred by the identification of several carcinogens in tobacco, of which the most common and strongest is N-nitrosamines, such as N-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.
Areca Nut Chewing
Betel nut or areca nut is currently considered a type 1 carcinogen that is frequently consumed along with betel leaves3,4. However, millions of people in Asia eat it raw, dried, roasted or as part of a betel quid. The use is also spreading to Pacific and Asian immigrant communities around the world. Affordable prepackaged betel nuts, such as pan masala, have recently become especially popular with young people. The inclusion of tobacco in betel nut significantly increases its carcinogenicity.
Epidemiological studies also suggest that drinking alcohol increases the risk of oral cancer by 2 to 6 fold and is an independent risk factor. Even so, the risk varies depending on the population and the individual’s subsites in the oral cavity5. However, the synergistic effect of tobacco and alcohol increases the risk of oral cancer. Various pathways by which alcohol may be carcinogenic include local effects with direct effects on cell membranes, mutations in alcohol-metabolizing enzymes, changes in cell permeability, and/or systemic effects such as immunodeficiency, malnutrition, and liver impairment.
Increased vegetable and fruit intake are specifically linked with a 40–50% reduction in oral cancer risk6. Some dietary aspects such as a lack of vegetables and fruits can cause 15–20% of oral cancers.
Other Risk Factors
While the liver metabolizes most carcinogens through the cytochrome p450 system. However, the defects in this system, in the form of genes (polymorphisms), are inherited, which increases the risk of many cancers. This risk is particularly significant for oral cancer and other head and neck cancers, but the relative risk is 1.5 or less7.
Polymorphisms in alcohol metabolizing enzymes also contribute to the risk. People with the rapidly metabolizing variant (allele) of alcohol dehydrogenase (ADH3 [1–1]) hence have a higher risk of developing oral cancer when they consume alcohol than those with a slower metabolizing form. This high risk also reaffirms the role of acetaldehyde as a related carcinogen.
Mate leaf infusions which are commonly consumed several times a day especially in parts of South America, elevate the risk of oral cancer by a small amount8.
Furthermore, recent evidence suggests that HPV infection may be an independent risk factor for cancers of the tonsils, tongue, and elsewhere at the base of the throat. HPV may also modify the process of carcinogenesis in some cases of tobacco- and alcohol-induced oral and throat cancers and may act as a major carcinogen causing cancer in non-smokers. 9.
Although it is now clear that chronic injuries from sharp teeth, dentures or restorations contribute to oral cancer, this high risk usually arises only if there are other localized risk factors10.
- 1.Johnson N, Warnakulasuriya S, Gupta P, et al. Global oral health inequalities in incidence and outcomes for oral cancer: causes and solutions. Adv Dent Res. 2011;23(2):237-246. doi:10.1177/0022034511402082
- 2.IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinog Risks Hum. 2004;83:1-1438. https://www.ncbi.nlm.nih.gov/pubmed/15285078
- 3.IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Betel-quid and areca-nut chewing and some areca-nut derived nitrosamines. IARC Monogr Eval Carcinog Risks Hum. 2004;85:1-334. https://www.ncbi.nlm.nih.gov/pubmed/15635762
- 4.IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Smokeless tobacco and some tobacco-specific N-nitrosamines. IARC Monogr Eval Carcinog Risks Hum. 2007;89:1-592. https://www.ncbi.nlm.nih.gov/pubmed/18335640
- 5.Radoï L, Paget-Bailly S, Cyr D, et al. Tobacco smoking, alcohol drinking and risk of oral cavity cancer by subsite: results of a French population-based case-control study, the ICARE study. Eur J Cancer Prev. 2013;22(3):268-276. doi:10.1097/CEJ.0b013e3283592cce
- 6.Lucenteforte E, Garavello W, Bosetti C, La V. Dietary factors and oral and pharyngeal cancer risk. Oral Oncol. 2009;45(6):461-467. doi:10.1016/j.oraloncology.2008.09.002
- 7.Lu D, Yu X, Du Y. Meta-analyses of the effect of cytochrome P450 2E1 gene polymorphism on the risk of head and neck cancer. Mol Biol Rep. 2011;38(4):2409-2416. doi:10.1007/s11033-010-0375-9
- 8.Deneo-Pellegrini H, De S, Boffetta P, et al. Maté consumption and risk of oral cancer: Case-control study in Uruguay. Head Neck. 2013;35(8):1091-1095. doi:10.1002/hed.23080
- 9.Heck J, Berthiller J, Vaccarella S, et al. Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Int J Epidemiol. 2010;39(1):166-181. doi:10.1093/ije/dyp350
- 10.Piemonte E, Lazos J, Brunotto M. Relationship between chronic trauma of the oral mucosa, oral potentially malignant disorders and oral cancer. J Oral Pathol Med. 2010;39(7):513-517. doi:10.1111/j.1600-0714.2010.00901.x