What Causes Oral Cavity and Oropharyngeal Cancers?

Doctors and scientists can’t say for sure what causes each case of oral cavity or oropharyngeal cancer. But they do know many of the risk factors and how some of them may lead to cells becoming cancer.

For human cells to be made, this mostly depends on the information in the cells’ DNA. DNA is the chemical in our cells that makes up our genes, which control how our cells work. We look like our parents because they are the source of our DNA. But DNA affects more than just how we look.

Some genes control when cells grow, divide, and die: 

• Genes that help cells normally grow, divide, and stay alive are called proto-oncogenes. When a proto-oncogene mutates (changes), the gene becomes abnormal and is then called an oncogene.  
• Genes that help keep cell growth under control or make cells die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA mutations (gene changes) that turn on oncogenes or turn off tumor suppressor genes. This leads to cells growing out of control. Changes in many different genes are usually needed to cause oral cavity and oropharyngeal cancer.

For more about how genes changes can lead to cancer, see Genes and Cancer.

Tobacco and alcohol and oral or oropharyngeal cancers

Scientists believe that some risk factors, such as tobacco or heavy alcohol use, may cause these cancers by damaging the DNA of cells that line the inside of the mouth and throat.

When tobacco and alcohol damage the cells lining the mouth and throat, the cells in this layer need to divide more often and make more copies of themselves. This increases the chance to make mistakes when copying their DNA, which may increase the possibility of becoming cancer.

Many of the chemicals found in tobacco can damage DNA directly. Scientists are not sure whether alcohol directly damages DNA, but they have shown that alcohol helps many DNA-damaging chemicals get into cells more easily. This may be why the combination of tobacco and alcohol damages DNA far more than tobacco alone. Acetaldehyde, a breakdown product of alcohol, is found in saliva (spit). It has been shown to get in the way of normal DNA repair, as well as disturb other functions of DNA. The level of acetaldehyde goes up as people drink more alcohol which may be one way alcohol damages the cells lining the oral cavity.

This damage can cause certain genes (for example, those in charge of starting or stopping cell growth) to not work well. Abnormal cells can begin to grow out of control, forming a tumor.

Human papillomavirus (HPV) and oral or oropharyngeal cancers

Certain types of human papillomavirus (HPV) infections (mainly HPV16), are important causes of most oropharyngeal (middle throat) cancers. HPV makes 2 proteins known as E6 and E7 which turn off some tumor suppressor genes, such as Rb and p53. In the throat, too much of the E6 and E7 proteins are made. 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.

The number of oropharyngeal cancers caused by HPV infections is going up. They tend to be found in younger people who don’t smoke or drink alcohol, and tend to have a better outcome (prognosis) than throat cancers that are not caused by HPV.

Inherited or acquired gene mutations and oral or oropharyngeal cancers

Some people inherit DNA mutations (changes) from their parents that increase their risk for developing certain cancers. But inherited gene mutations are not believed to cause very 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. These people are more sensitive to the cancer-causing effects of tobacco smoke, alcohol, and certain industrial chemicals. 

Acquired gene mutations are gene changes that usually 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.