Page 9 Complete Your CE Test Online - Click Here Diethylstilbestrol (DES) is a form of estrogen that was given to some pregnant women in the U.S. between 1940 and 1971 to prevent miscarriages, premature labor, and related problems associated with pregnancy [169]. DES came in many forms, including pills, creams, and vaginal suppositories. Women who took DES during pregnancy may have an increased risk of breast cancer, as may their daughters. Their daughters (“DES daughters”) have an increased risk of a cancer of the vagina or cervix. DES daughters should have annual pap smears from the vagina and cervix, and follow up any abnormalities with colposcopy. The National Cancer Institute recommends that DES daughters rigorously follow the routine breast cancer screening recommendations for their age group [160]. The possible effects on the sons and grandchildren of women who took DES during pregnancy are still being studied [169]. Other drugs There are a number of other drugs on the American Cancer Society combined list of known carcinogens. Adriamycin, alkylating agents, azacitidine, busulfan, CCNU, chlorambucil, chlorozotocin, cisplatin, cyclophosphamide etoposide, melphalan, nitrogen mustard, procarbazine, semustine, and tamoxifen and are some of the cancer treatment drugs that have made the list so far [32]. As with radiation therapy, there are safety trade-offs; a low risk of a possible second cancer in the future is a risk worth taking to most people facing the much more immediate threat of death from existing cancer. Phenacetin, chloral hydrate, chloramphenicol, pioglitazone, and cyclosporine are drugs on the known carcinogen list that are not designated for cancer treatment [32]. Infectious agents Certain infectious agents can cause cancer in infected people or increase the risk that cancer will form. Some viruses can disrupt normal controls on cell growth and proliferation. They may also increase the chance that a person will be affected by other cancer risk factors, such as UV radiation or substances in tobacco smoke that cause cancer. Some viruses, bacteria, and parasites also cause chronic inflammation, which may lead to cancer. Most of the viruses that are linked to an increased risk of cancer can be transmitted through blood and/or other body fluids. People can lower their risk of infection from many of these by getting vaccinated, not having unprotected sex, and not sharing needles or equipment if they inject drugs [172]. Globally, infectious agents have been estimated to cause 18% of all cancer cases [237]. The burden of cancers caused by infections is much greater in developing nations (26%) than in developed nations (8%) [148]. Human papillomaviruses (HPVs) Infection with high-risk types of human papillomavirus (HPV) cause nearly all cervical cancers. Infection with an oncogenic strain of HPV is considered a necessary event for later development of cervical cancer, and vaccine-conferred immunity (available to younger people before sexual initiation) results in a marked decrease in precancerous lesions. Oncogenic strains of HPV also cause most anal cancers and many oropharyngeal, vaginal, vulvar, and penile cancers. In the United States, the Advisory Committee on Immunization Practices (ACIP) recommends that children aged 11 to 12 receive an HPV vaccine series that helps to prevent infection with the types of HPV that cause most HPV-associated cancers. Children as young as age nine and adults as old as 26 can also be vaccinated. If an infectious agent is a cause of cancer, then effective anti-infective interventions would be expected in most instances to be effective cancer prevention interventions. This is the expectation with vaccines that protect against infection with oncogenic strains of HPV [148]. HPV infections in the cervix can be found with specific tests. Although HPV infections themselves cannot be treated, the cervical cell changes these infections can cause over time can be treated to prevent future cancers [172]. Human immunodeficiency virus (HIV) Over time, the human immunodeficiency virus (HIV) decimates the immune system which can allow uncontrolled opportunistic infections, including oncogenic agents. People infected with HIV have an increased risk of Kaposi’s sarcoma, lymphoma, and cancers of the cervix, liver, lung, and anus. HIV infection often does not cause obvious symptoms until the infection progresses to Acquired Immunodeficiency Syndrome (AIDS) [172]. In addition to the usual known AIDS-related opportunistic cancers, people with HIV have higher risk of more common cancers as well and should be carefully screened. Some cases, (e.g. cervical cancer) should be considered high-risk for screening purposes. People with untreated HIV are at fairly high risk of a number of cancers. People whose HIV infection is treated with effective combination antiretroviral therapy (cART) typically have better immune function and much longer survival than those who are not [217]. Hepatitis B virus and hepatitis C virus (HBV and HCV) Chronic infections with HBV or HCV can cause liver cancer. Since the 1980s, infants in the U.S. and most other countries have been routinely vaccinated against HBV infection. Adults who have not been vaccinated against HBV and have an increased risk of HBV infection should be vaccinated as soon as possible. Vaccination for HBV is especially important for healthcare workers and other professionals who come into contact with human blood [172]. The CDC also recommends that everyone in the U.S. born from 1945 through 1965 be tested for HCV, along with other populations at increased risk for HCV infection. These infections can be asymptomatic, but tests can show whether a person has been infected with either virus. People who test positive for either of these might benefit from treatment, and should also learn how to avoid infecting other people [172]. As of early 2016, there is no vaccine for HCV, although clinical trials are in progress. Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) HTLV-1 is a retrovirus (in the same class as HIV) that can cause a type of lymphocytic leukemia or lymphoma called adult T-cell leukemia/ lymphoma (ATL) [172]. HTLV-1 is transmitted the same ways as HIV (e.g. unprotected sex, shared needles, to infants from mother while in utero, and breastfeeding), although it does not cause AIDS or AIDS- like illness. HTLV-1 is most often found in parts of South America, the Caribbean, Central Africa and parts of Japan. Infection with HTLV-1 is rare in the U.S., but people who engage in high-risk behaviors are more likely to acquire the virus. Once a person contracts the virus, and usually after a long asymptomatic period spanning decades, the chance of developing ATL might be as high as 5% [29]. Epstein-Barr virus (EBV) Infection with EBV, a type of herpes virus that is best known for causing mononucleosis, is life-long (as with other herpes viruses). Most U.S. adults are infected with EBV, although not everyone who becomes infected has symptoms of mononucleosis. After the initial infection, the viral infection is usually asymptomatic, and EBV does not cause serious illness for most people [29]. EBV has been linked to a slightly increased risk of fast-growing lymphomas and cancers of the stomach and nasopharynx [172]. Human herpesvirus 8 (HHV8) HHV8, i.e. Kaposi’s sarcoma-associated herpes virus (KSHV), also causes a life-long infection. In people who are immunocompromised, KSHV can cause Kaposi’s sarcoma, a slow-growing cancer that typically appears on the skin as purple or brown lesions, but can also affect the mucosa in organs such as the lungs or the gut [172]. Kaposi’s sarcoma is endemic in some countries, especially in older people, but in the U.S. is most often linked with HIV infection. This virus has also been linked to some rare blood cancers and multicentric Castleman’s Disease [29]. Merkel cell polyomavirus (MCPyV) MCPyV can cause Merkel cell carcinoma, which is a rare type of aggressive cancer affecting cutaneous neuroendocrine cells. About 80% of people are infected with MCPyV by adulthood, but the virus rarely causes symptoms or cancer. In a few, usually fair-skinned people older than 50 years of age, the virus can lead to Merkel cell cancer [29]. This malignancy occurs in skin that is frequently exposed to sunlight, and more often affects people in their 70s, those with HIV, and those who are otherwise immunosuppressed (e.g. organ transplant patients). Even though Merkel cell carcinoma is relatively rare, its incidence in the U.S. tripled in the two decades after the 1990s and continues to climb [262].