Oral Cavity and Oropharyngeal Cancer Causes, Risk Factors, and Prevention

Human papillomavirus (HPV) is a group of more than 150 types of viruses. Infection with certain types of HPV can cause some forms of cancer, including cancers of the penis, cervix, vulva, vagina, anus, mouth, and throat.

Certain types of HPV infections, mainly HPV16, are important causes of most oropharyngeal cancers.

• Human papillomavirus DNA (a sign of HPV infection) is found in about 2 out of 3 oropharyngeal cancers.
• It is found in a much smaller portion of oral cavity cancers. 

HPV makes 2 proteins known as E6 and E7 which turn off some tumor suppressor genes, such as Rb and p53. This may allow the cells lining the oropharynx to grow out of control and to develop changes in more genes, which in some cases can lead to cancer.

Recent increases in oropharyngeal cancers linked to HPV

The number of oropharyngeal cancers linked to HPV has risen greatly over the past few decades. These cancers are becoming more common in younger people who have a history of multiple sex partners (including oral sex) and no history of alcohol abuse or tobacco use.

Outcomes for HPV-related oropharyngeal cancers

Oropharyngeal cancers linked to HPV infection tend to have better outcomes (prognoses) than tumors not caused by HPV because chemotherapy and radiation treatments work better for these cancers.

This improvement in outcomes is not seen in people with HPV-related oropharyngeal cancers who also smoke.

See HPV (human papillomavirus) to learn more about HPV infection and vaccines to prevent it.

Some people inherit DNA mutations (changes) from their parents that increase their risk of developing certain cancers. These are called inherited gene mutations.

Inherited gene mutations are not believed to cause many cancers of the oral cavity or oropharynx. Even though inherited gene mutations rarely cause these cancers, some people seem to inherit a poor ability to detoxify (break down) certain types of cancer-causing chemicals. They are more sensitive to the cancer-causing effects of tobacco smoke, alcohol, and certain industrial chemicals.

Acquired gene mutations are gene changes that happen during life, rather than being inherited. These gene mutations often result from exposure to cancer-causing chemicals, like those found in tobacco smoke. Several different gene changes are probably needed for cancer to develop, and not all of these changes are understood at this time.

Scientists believe that tobacco use and/or heavy alcohol use increases the risk for development of these cancers by damaging the DNA of cells that line the inside of the mouth and throat. 

When this happens, the cells lining the mouth and throat divide more often and make more copies of themselves. This increases the chance of mistakes when their DNA is copied, and can cause certain genes to not work well, including genes in charge of starting or stopping cell growth. Abnormal cells can begin to grow out of control, forming a tumor.

Tobacco use

Many of the chemicals found in tobacco can damage DNA directly. The more you smoke, the greater your risk.

• Smoke from cigarettes, pipes, and cigars all increases your risk of getting these cancers. 
• Oral tobacco products (snuff, dip, spit, chew, or dissolvable tobacco) are linked with cancers of the cheek, gums, and inner surface of the lips. Using oral tobacco products for a long time is linked to a very high risk.

Alcohol use 

Scientists aren’t sure whether alcohol directly damages DNA, but they have shown that alcohol helps many DNA-damaging chemicals get into cells more easily. People who drink moderate to heavy amounts of alcohol have a higher risk than those who drink light amounts.

Smoking and drinking alcohol together

Smoking and drinking alcohol together multiplies the risk of these cancers. The risk of these cancers in people who drink and smoke heavily is about 30 times higher than the risk in people who don’t smoke or drink.

In Southeast Asia, South Asia, and certain other areas of the world, many people chew betel quid, which is made up of areca nut (betel nut), spices, lime, and other ingredients. Many people in these areas also chew gutka, a mixture of betel quid and tobacco.

People who chew betel quid or gutka have an increased risk of cancer of the mouth.

Oral cavity and oropharyngeal cancers are twice as common in men than in women. This might be because men have been more likely to use tobacco and alcohol in the past. HPV-related oropharyngeal cancers are also seen more often in men.

Several studies have found that a diet low in fruits and vegetables is linked with an increased risk of cancers of the oral cavity and oropharynx. Eating more plant-based foods, such as non-starchy vegetables and whole fruit, might help people reduce their risk of oropharyngeal and laryngeal cancer from poor nutrition.

People with long-term inflammatory tongue conditions may have a higher risk of developing tongue cancer. These conditions may include tongue inflammation (glossitis), thinning (atrophy), enlargement (hypertrophy), or chronic burning pain (glossodynia).

Sunlight is the main source of UV light for most people. Cancers of the lip are more common in people who have outdoor jobs where they are exposed to sunlight for long periods of time.

People with syndromes caused by inherited changes (mutations) in certain genes have a very high risk of mouth and middle throat cancer.

Fanconi anemia

People with this syndrome often have blood problems at an early age, which may lead to leukemia or myelodysplastic syndrome. They also have a very high risk of cancers of the mouth and throat.

Dyskeratosis congenita

This is a genetic syndrome that can cause aplastic anemia, skin rashes, and abnormal fingernails and toenails. People with this syndrome also have a very high risk of developing head and neck cancers at a young age, especially cancers of the mouth and throat.

Some studies have suggested mouthwash with a high alcohol content might be linked to a higher risk of oral and oropharyngeal cancers. Other research has questioned these results. Studying this possible link is complicated by the fact that people who use tobacco and alcohol, and already have an increased risk of these cancers, are more likely to use mouthwash than people who neither smoke nor drink.

It's been suggested that long-term irritation of the lining of the mouth caused by poorly fitting dentures is a risk factor for oral cancer. Many studies have found no increased risk in denture wearers overall.

Poorly fitting dentures tend to trap agents that have been proven to cause oral cancer, such as alcohol and tobacco particles. Denture wearers should have them checked regularly by a dentist to ensure a good fit. All denture wearers should remove their dentures at night and clean and rinse them thoroughly every day.

Studies have suggested the overall health of the mouth, teeth, and gums may impact oral cavity and oropharyngeal cancer risk because of changes in the normal bacteria in the mouth. More research is needed, but regular dental visits, as well as brushing and flossing, may lessen these risks and have many other health benefits, too.