Cancer and Infectious Disease
Cancer and Infectious Disease
Cancer is not normally considered an infectious disease. Yet there is an important link between some infectious agents and certain cancers. Research has shown that chronic infection with certain viruses, and at least one bacterium, can increase the risk of these cancers. For example, human papillomavirus (HPV) is the leading cause of cervical cancer, while chronic hepatitis B virus or hepatitis C virus infection may develop into liver cancer. These viruses are now listed as carcinogens (cancer-causing substances) by the U.S.—andother— governments. Viruses have a number of ways of causing changes in cells that can cause them to divide uncontrollably, leading to the formation of a tumor. The recognition that infection can play a role in cancer is leading to new approaches to prevention and treatment. For instance, vaccination against HPV is now being introduced for girls and young women, because there is now good evidence that it protects them against cervical cancer in later life.
It has long been known that certain viruses can cause cancer in animals. Danish researchers Wilhelm Ellermann and Oluf Bang discovered a virus that spreads leukemia among chickens in 1908. Then, in 1911, Peyton Rous (1879–1970) of the Rockefeller Institute in New York identified a virus responsible for sarcoma (a cancer of a connective tissue, like bone or cartilage) in chickens. By the 1930s, it was recognized that viruses played a role in several animal cancers. However, the significance of Rous's work for human cancer was not appreciated for many years; he was finally awarded a Nobel Prize in physiology or medicine in 1966.
The first discovery of a human cancer virus came from research carried out in Uganda in the 1950s by the Irish surgeon Denis Burkitt (1911–1993). He discovered a type of cancer of the jaw that affected young children. The disease became known as Burkitt's lymphoma, and it is still the most common tumor among African children. Tumor samples were analyzed by Anthony Epstein back in London, who discovered the presence of a new type of herpes virus, named Epstein-Barr virus (EBV). Originally, it looked as if EBV was carried by mosquitoes, because Burkitt's lymphoma was found in areas where malaria is endemic. EBV infection is very common, affecting around 90% of the world's population, most of whom do not get Burkitt's lymphoma. It is not transmission by mosquitoes, but it is exposure to malaria in combination with EBV infectionthat allows cancer to develop. This fits what scientists now understand about cancer—that it develops in stages, over a long period of time, under the influence of a combination of different risk factors, both genetic and environmental. EBV has also been linked to other cancers, including nasopharyngeal cancer, which affects the area at the back of the nose, and it also is found in around half of Hodkgin's lymphoma cases.
WORDS TO KNOW
CARCINOGEN: A carcinogen is any biological, chemical, or physical substance or agent that can cause cancer. There are over one hundred different types of cancer, which can be distinguished by the type of cell or organ that is affected, the treatment plan employed, and the cause of the cancer. Most of the carcinogens that are commonly discussed come from chemical sources artificially produced by humans. Some of the better-known carcinogens are the pesticide DDT (dichlorodiphenyltrichloroethane), asbestos, and the carcinogens produced when tobacco is smoked.
RETROVIRUS: Retroviruses are viruses in which the genetic material consists of ribonucleic acid (RNA) instead of the usual deoxyribonucleic acid (DNA). Retroviruses produce an enzyme known as reverse transcriptase that can transform RNA into DNA, which can then be permanently integrated into the DNA of the infected host cells.
The human papillomaviruses (HPVs) are a large group of viruses that can cause warts on the skin, mouth, and genitals. HPV infection is very common among people who are sexually active, and certain strains can cause cervical cancer. Most women who have cervical cancer show signs of infection with one of these strains. The risk of contracting HPV infection increases with the number of sexual partners a woman has.
Hepatitis B virus (HBV) and Hepatitis C virus (HCV) may cause chronic viral hepatitis, an infection of the liver that is linked to an increased risk of hepatocellular (liver) cancer. In the United States, about one-third of cases of liver cancer are related to HBV and HCV.
The human immunodeficiency virus (HIV) does not, in itself, increase the risk of cancer. However, HIV infection does increase the risk of infection by the human herpes virus 8 (HHV-8), which can lead to a skin cancer called Kaposi's sarcoma (KS). Indeed, it was the appearance of KS among homosexual men in the United States in the early 1980s that first alerted the medical community to the existence of HIV. Before the emergence of HIV, KS was rare in the West, although it was known in central Africa and the Middle East. HHV-8 is isolated from most KS tumors. Meanwhile, the human T-lymphotrophic virus (HTLV-1) is associated with a blood cancer called adult T-cell leukemia (ATL). Like HIV, HTLV-1 is a retrovirus—a type of virus whose genetic material is made of RNA rather than DNA. Both HIV and HTLV-1 are related to retroviruses known to cause leukemia in animals.
Finally, infection with the bacterium Helicobacter pylori increases the risk of stomach cancer. H. pylori is unusual because it can survive the acid conditions of the stomach. Infection causes inflammation of the stomach lining, increasing the risk of both stomach ulcers and stomach cancer. About one-third of the U.S. population has evidence of H. pylori infection. Although around one-half of all cases of stomach cancer are linked to the infection, most of those who do carry the infection will not develop cancer.
Viruses and bacteria can raise the risk of cancer in various ways. They can cause chronic inflammation of the tissue they infect. Or, like HIV, they may suppress immunity and allow cancer-causing viruses to take hold. Immune suppression after an organ transplant is an important cause of HBV-associated lymphoma, for example. Some viruses can invade cells directly and alter their genetic machinery, disrupting normal control over cell division. But infection is only ever one link in a chain of events leading to tumor formation. Other factors, such as smoking, diet, or genetic disposition, may be equally important. The chain may be broken using a vaccine, which prevents infection, or by an antibiotic, which eliminates it. The introduction of a vaccine against HBV in Taiwan 25 years ago led to reduced rates of liver cancer in the country. There is, however, no vaccine against HCV— although research is ongoing. More recently, vaccines against HPV have been developed. In some clinical trials, this has provided girls and young women with 100% protection from infection. One of these, Gardasil, is now approved in some countries for use in females aged nine to 26, to protect them from cervical cancer. Eliminating H. pylori with antibiotics can prevent new stomach cancers from developing in patients who have had superficial stomach cancers removed.
The viruses described above, and H. pylori, have a well established link to cancer. The possibility that the role of infection in cancer may be even wider is being investigated. For example, there is evidence that infection with Chlamydia trachoma could increase the risk of cervical cancer, and a related species, Chlamydia psittaci, could be linked to a rare cancer of the eyes known as mucosa-associated lymphoid tissue lymphoma. A monkey virus called SV40 has been linked to mesothelioma, a cancer of the lining of the chest wall, in which asbestos exposure is another risk factor. Researchers in England have even suggested that common infections contracted either in the womb or during childhood may lead to clusters of childhood cancers that have previously been attributed to other environmental factors, such as overhead power lines.
IN CONTEXT: MONITORING DISEASE
Congress established the National Program of Cancer Registries (NPCR) with the Cancer Registries Amendment Act in 1992. The Centers for Disease Control and Prevention (CDC) administers the program and collects data related to the occurrence, type, extent, location, and treatment of cancers.
Cancer registries based in individual U.S. states within the United States also collect and analyze data related to cancers.
IN CONTEXT: DISEASE BURDEN OF CANCER
According to the National Institutes of Health Fact Book Fiscal Year 2004: “Cancer costs (the United States) an estimated $210 billion overall in 2005, including nearly $136 billion for lost productivity and more than $70 billion for direct medical costs.”
Most viruses and bacteria are not known to be a risk factor for cancer, and cancer is not, in itself, contagious. Moreover, the majority of people infected with agents known to be carcinogenic will not actually contract cancer; the presence of one or more other risk factors is necessary for cancer to develop.
Worldwide, infection is linked to 15 to 20% of all cancers. Other important contributing factors include smoking, diet, sunlight exposure, and genetics. In developed countries, the cancers that can be linked to infection tend to be much less common than they are in developing countries. For example, cervical cancer is becoming rare in the West because of the availability of the Pap smear, a test that checks for changes in the cells of a woman's cervix and the basis of national screening programs. Cure rates of cases caught at an early stage are very high. But cervical cancer is still the second most common cancer among women worldwide. Vaccination or screening, if it could be afforded, could help cut the global toll from the disease. Nasopharyngeal cancer is more common in Africa and Southeast Asia. In China, a high consumption of salt combines with EBV to increase the risk of this disease. HBV and HCV infection, and hepatocellular cancer, are all more common in developing countries, while ATL is found mainly in southern Japan, the Caribbean, Central Africa, and Latin America. Meanwhile, stomach cancer is the fourth most common cancer worldwide.
In 2007, Texas became the first state to consider mandatory vaccination against HPV for girls entering the sixth grade. The vaccine, Gardasil®, was approved for use in girls and women ages nine to 26 in 2006; it protects against the four types of HPV that are responsible for causing 70% of cervical cancers. After concerns regarding parental rights, vaccine availability, and the high cost of the vaccine arose, plans to mandate vaccination against HPV were put on hold. Costing over $350 for the three-injection series, Gardasil® is one of the most expensive vaccines ever produced. This expense makes distributing the vaccine to young women in developing countries impractical at the present time without corporate, government, or philanthropic action. The Bill and Melinda Gates Foundation and Merck, the manufacturer of the vaccine, plan a cooperative effort to distribute and administer Gardasil® to women in developing countries throughout the world.
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National Institutes of Health. “List of Cancer-Causing Agents Grows.” January 31, 2005. <http://www.nih.gov/news/pr/jan2005/niehs-31.htm> (accessed February 19, 2007).