What Causes Laryngeal and Hypopharyngeal Cancers?

We don’t know what causes each case of laryngeal or hypopharyngeal cancer. But we do know many of the risk factors for these cancers (see Risk Factors for Laryngeal and Hypopharyngeal Cancers) and how some of them cause normal cells to become cancer.

The development of normal human cells mostly depends on the information contained 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 grow, divide, and stay alive are called proto-oncogenes
• 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 proto-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 laryngeal and hypopharyngeal cancer.

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

Tobacco and alcohol: Scientists believe that some risk factors, such as tobacco or heavy alcohol use, cause these cancers by damaging the DNA of the cells that line the inside of the larynx and hypopharynx.

Inherited and acquired gene mutations: Some people inherit DNA mutations (changes) from their parents that greatly increase their risk for developing certain cancers. But inherited gene mutations are not believed to cause very many cancers of the larynx or hypopharynx.

Gene changes related to these cancers usually happen during life, rather than being inherited. These acquired mutations often result from exposure to cancer-causing chemicals, like those found in tobacco smoke. An acquired change in the p16 tumor suppressor gene seems to be important in laryngeal and hypopharyngeal cancers, although not all these cancers have this change. Several different gene changes are probably needed for cancer to develop, and not all of these changes are understood at this time.

Inherited mutations of proto-oncogenes or tumor suppressor genes rarely cause these cancers, but 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.

Human papillomavirus (HPV): Some types of HPV are important causes of middle throat (oropharyngeal) cancers and are sometimes seen with laryngeal cancers. HPV has two proteins known as E6 and E7 which turn off some tumor suppressor genes, such as p53 and Rb. This may allow the cells lining the larynx to grow out of control and to develop changes in additional genes, which in some cases can lead to cancer.