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Infectious Agents and Cancer
Overview of Cancer and Infectious Agents
Infectious agents are second only to tobacco use as a potentially preventable cause of cancer in humans. Estimates vary between 15% and 30% as to the percentage of cancers worldwide that are associated with an infectious etiology. 1,2 The burden is greater in the developing world, but the impact even in the United States and other developed countries is significant. Specific viruses, parasites, and bacteria are now associated with specific human cancers. These are discussed in some detail in this chapter.
There are three major mechanisms by which an infectious agent can cause a cancer, and these may involve the initiation as well as the promotion of carcinogenesis. 3 The first is perhaps the most common, resulting from the infectious agent causing a persistent infection with chronic inflammation. This can result in the formation of reactive oxygen and nitrogen species by macrophages at the site of the infection. These reactive molecules can damage DNA and proteins as well as membranes and thus contribute to carcinogenesis. 4 Chronic inflammation due to the persistent infection can then lead to repeated cycles of cell damage and cellular proliferation. Cells that are cycling in the presence of reactive molecules are more likely to acquire genetic mutations that could contribute to the initiation as well as the promotion of cancer. A second mechanism involves the direct participation of the infectious agent in the transformation of the cell through the activation of a cellular oncogene pathway or the inactivation of a tumor suppressor gene. A third mechanism, relevant to the human immunodeficiency virus (HIV), is that the infection may result in immunosuppression and the decreased recognition of infected or transformed cells by the host immune system. Indeed, many of the cancers observed in immunosuppressed patients, such as those infected with HIV, are those that have been associated with other viruses.
The recognition of an infectious etiology for specific cancers provides the opportunities to prevent those cancers by preventing or controlling the infections. Depending on the infectious agent, this could involve public health measures or changes in cultural practices. It could also involve the development of vaccines to prevent the initial infections, as has now been achieved for hepatitis B virus (HBV) and the genital-tract human papillomaviruses (HPVs). It could also involve the treatment of the infections with specific therapeutics or the development of novel therapies for those agents for which there are not yet specific or effective drugs.
