Causes of Oral and Oropharyngeal cancer

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Oral cancer has been observed as a multifactorial disease in which various genetic, etiological and environmental factors such as genetic causes, tobacco and alcohol consumption, HPV infection, immunosuppression, diet and nutrition, socioeconomic status, ethnicity and race, oral hygiene and indoor air pollution has been found to increase the risk of oral and oropharyngeal cancer.


Oral cancer has been observed as a multifactorial disease in which environmental, genetic and epigenetic factors are involved in its aetiology. Some of the factors associated with the cause of oral and oropharyngeal cancer have been described below:

Genetic causes

The p53 polymorphism (Arg72Pro) has been suggested to increase susceptibility to oral cancer in the presence of HPV infection. Exogenous carcinogens cause DNA damage and the inactivation of tumor suppressor genes (TSGs) to cause cancer. The genetic change in oral cancer results from a dominant or recessive change. In dominant mutations, proto-oncogenes and some TSGs predominate, whereas in recessive mutations, growth-inhibitory pathway genes or normal TSGs are affected by the increased loss of function, respectively. Specific variations in genes that control DNA repair, apoptosis, immortalization, proliferation, growth factor receptors, invasion, angiogenesis, transcription factors, and signalling reveal differences between upper aerodynamic cancer and normal epithelial cells. These genetic mutations cause a variety of abnormalities in the normal genetic process. In addition to genetics, epigenetic changes such as DNA methylation, micro RNA-induced silencing (miRNA), and histone modifications are involved in oral cancer​1​.

Tobacco, betel quid and alcohol consumption

The main oral cancer risk factors include smoking and alcohol abuse. Several important epidemiological studies from different countries confirm the risks associated with these two lifestyles. All types of smoking (tobacco or cigars) have similar additional risks. There is also evidence that certain alcoholic beverages (wine, beer, and spirits) have different effects on oral cancer.

The use of smokeless tobacco (ST) also significantly increases the risk of oral cancer. However, most chewing tobacco is marketed as a mixture of betel nut. Betel quid is carcinogenic to humans (with or without tobacco)​2​ and is a significant risk factor for Asians.

Higher risks from these different medications and exposures (smokers, regular users of alcohol and betel nut, adjusted for each other) have been consistently reported across cohorts compared to non-users.

Human papillomavirus infection (HPV)

There is substantial evidence from a recent study that HPV infection (subtypes 6 and 16) is a specific risk factor for oropharynx cancer (the back of the tongue, tonsils, and the visible part of the throat that is continuous with the mouth). The etiological role of HPV in cervical cancer is well established. New data suggest that rates of oral and throat cancer cases are associated with HPV infection and seropositive status (particularly in young people with a history of alcohol or tobacco addiction).


An increase in the incidence of lip cancer has been reported after kidney transplantation and is significantly associated with the use of immunosuppressants (azathioprine and cyclosporine)​3​. Long-term use of immunosuppressants (azathioprine) to treat inflammatory bowel disease (Crohn’s disease) may increase the risk of tongue cancer​4​.

Diet and nutrition

There is evidence that there is a positive association between a low intake of fruits and vegetables and an increased oral cancer risk. A higher risk is also associated with an increased intake of processed meat products​5​. People who consumed a lot of fresh fruits and vegetables were observed to have a 50% reduced risk of oral cancer​6​.

Mate drinking

Several epidemiological studies have explored the role of mate drinking in increasing the risk of oral cancer. A meta-analysis confirmed this association and assessed an increased risk of oral cancer among mate consuming individuals​7​. The effect of mate when drunk hot has not been demonstrated, but the high temperature of this beverage may act as a co-factor and cause chronic irritation in the open oral mucosa.

Socio-economic status

Oral cancer is more common in people from lower socioeconomic backgrounds and people living in marginalized areas. This unequal distribution was thought to be due to the higher prevalence of smoking, alcohol use, and malnutrition in these groups. However, new research suggests that low socioeconomic status (measured in a variety of ways, including occupation, income, and education) is an important risk factor for oral cancer, regardless of lifestyle​8​.

Ethnicity and race

It is estimated that susceptibility to oral cancer from tobacco and alcohol use varies by race and ethnicity. The incidence of oral cancer in various racial/ethnic groups around the world and in some regions varies by ethnicity​9​. South Asians have a higher risk of oral cancer than people from other countries, and black men (Americans) have a higher risk in comparison to Caucasians of increased oropharyngeal cancer risk.

Oral hygiene and dentition

Some epidemiological studies have associated increased oral cancer risk with poor oral hygiene and poor dentures (damaged restorations, sharp teeth, and poorly fitting dentures).

Oral microbes can also be a factor in chronic alcohol users. This is because some microorganisms promote the metabolism of ethanol to acetaldehyde (a potent carcinogen) in the mouth. This may promote the formation of acetaldehyde in the oral cavity, which may be involved in oral cancer cells in chronic alcoholics​10​.

Indoor air pollution

A study in Germany and Brazil found that daily exposure to fossil fuels from stove heating (including oil, coal, or firewood) might increase the risk for oral cancers due to increased indoor air pollution​11​. Volatile carcinogenic compounds formed during cooking have been linked to mortality from oral cancer in cooks​12​.


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    Ali J, Sabiha B, Jan H, Haider S, Khan A, Ali S. Genetic etiology of oral cancer. Oral Oncol. 2017;70:23-28. doi:10.1016/j.oraloncology.2017.05.004
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    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.
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    van L, Grulich A, McDonald S, et al. Immunosuppression and other risk factors for lip cancer after kidney transplantation. Cancer Epidemiol Biomarkers Prev. 2009;18(2):561-569. doi:10.1158/1055-9965.EPI-08-0919
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