More about infectious agents, viruses and their impact on cancers

Introduction: Cancer-Causing Infections

Infectious agents, such as viruses and bacteria, are the causes of several common cancers. Infection with the bacterium Helicobacter pylori predisposes to gastric cancer. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with liver cancer, and Epstein-Barr virus (EBV) is associated with lymphoma and nasopharyngeal cancer. Human papillomavirus (HPV) is a major cause of cervical, anal, penile, and oropharyngeal cancer. Together, infection-associated tumors make up nearly 20% of all cases of cancer worldwide, causing more than 2 million malignancies per year. Most of these cases occur in developing countries. Under normal circumstances, immune surveillance helps to keep many of these virus-associated cancers in check, but in immunocompromised persons, such as those with late-stage HIV infection, the incidence and aggressiveness of these cancers increase. HBV and HPV vaccines are effective and in use, and vaccines against other cancer-causing agents are in development. Because many virus-associated cancers occur in the developing world (such as EBV-associated Burkitt’s lymphoma in Africa and HBV-associated hepatocellular carcinoma [HCC] in Asia), the development and deployment of vaccines to prevent infection with HPV, HBV, HCV, and EBV can serve as effective preventative tools to reduce the burden of cancer morbidity and mortality worldwide.

In the developing world, cancer is estimated to afflict 10 million people per year. Worldwide efforts to prevent cancer have generally focused on behavioral changes, such as smoking cessation. Because infectious agents cause some of the more common human cancers, understanding the role of the immune system is necessary to maximize cancer prevention strategies. The immune system has an endogenous role in preventing some cancers and can be stimulated with vaccines to prevent infection with cancer-causing viruses.

One of the paradoxes of cancer biology is that a lack of immune surveillance (such as in HIV-infected individuals or immunosuppressed organ transplant recipients) can lead to cancer, and chronic inflammation due to persistent infection can also do so. Chronic inflammation as a result of HBV or HCV infection leads to HCC, usually after the patient progresses to cirrhosis. In gastric cancer, nearly 60% of all cases in developed countries and 75% of cases in developing countries are attributable to chronic infection with H pylori. It is likely that chronic inflammation due to H pylori leads to intestinal metaplasia of the gastric epithelium and eventually to gastric cancer. Long-term infection with HPV and EBV leads to transfer of oncogenes present in the viral genome to human cells, thereby promoting cancer development.

Harnessing the immune system to prevent or clear cancer is a major goal of cancer research. Vaccination campaigns have been enormously successful in reducing the global burden of infectious diseases. A worldwide infrastructure exists for the manufacture, distribution, and administration of vaccines in urban, suburban, and rural areas. The use of vaccines to prevent cancer caused by chronic infection with oncogenic agents has had a substantial benefit in the developed world and could have a major effect on cancer incidence in the developing world.

Human Papilloma Virus and Cancers of the Anogenital Tract and Oropharynx

HPVs are commonly spread through sexual contact. These viruses are the cause of benign genital warts, and subtypes 16, 18, 31, 33, and 35 are the major subtypes that cause cervical, anal, and head and neck (primarily oropharyngeal) cancer. HPV infection is associated with 100% of cases of cervical cancer. The incidence of infection with HPV is high and very common. The number is so large and different than the incidence of related cancers, because in the vast majority of people the immune system clears most infections in less than 2 years. However, more than 500,000 new cases of cervical cancer are estimated to occur worldwide in 2010. The worldwide burden of all HPV origin cancers in 2013 was about 650,000 new cases per year. Routine Papanicolaou smears can monitor for early signs of cervical cancer, but many at-risk women in the United States and elsewhere; particularly 3rd world countries, do not receive appropriate gynecologic care and screening examinations. These women are more likely to be from nonwhite, lower-income, and immigrant groups, and they are more likely to develop and die of cervical cancer.

During the past 30 years, the incidence of aggressive serotype HPV-associated squamous-cell carcinoma of the anus has increased. This increase largely began in men who have sex with men, but increases in women have also been observed. HPV is also associated with cancer of the vagina, vulva, and penis, although these are much less common than cervical cancer.

Squamous-cell carcinoma of the oropharynx and head and neck has been historically associated with tobacco and alcohol use, but HPV serotypes 16 is commonly observed in a subset of persons with this cancer. In oropharyngeal cancers of the tonsil, base of tongue and the oropharynx itself, it is now the dominant cause Of interest, the percentage of HPV-positive oral cancers is reported to be increasing in several countries. This increase is attributed to changing sexual practices, suggesting that HPV-associated oral cancers, like HPV-associated anal and cervical cancer, should be considered a sexually transmitted infection.

Hepatitis B and C Viruses and Hepatocellular carcinoma

Chronic Hepatitis B Virus infection is highly prevalent throughout the developing world, particularly in Asia and Africa, where some countries have a prevalence rate as high as 12% of the total population. It is estimated to cause more than 1 million annual deaths worldwide, with one third of these deaths caused by Hepatocellular carcinoma and the remainder by cirrhosis. Chronic Hepatitis B infection confers a 20 times increased risk for Hepatocellular carcinoma. Hepatitis B vaccination is now included in the standa