Viruses are etiologic factors in the development of several types of human tumors, including two of great significance worldwide—cervical cancer and liver cancer. At least 15–20% of all human tumors worldwide have a viral cause. The viruses that have been strongly associated with human cancers are listed in Table 43-1. They include human papillomaviruses (HPVs), Epstein-Barr virus (EBV), human herpesvirus 8, hepatitis B virus, hepatitis C virus, and two human retroviruses plus several candidate human cancer viruses. New cancer-associated viruses are being discovered by the use of molecular techniques. Many viruses can cause tumors in animals, either as a consequence of natural infection or after experimental inoculation.
TABLE 43-1Association of Viruses With Human Cancersa |Favorite Table|Download (.pdf) TABLE 43-1 Association of Viruses With Human Cancersa
|Virus Family ||Virus ||Human Cancer |
|Papillomaviridae ||Human papillomaviruses ||Genital tumors |
| ||Squamous cell carcinoma |
| ||Oropharyngeal carcinoma |
|Herpesviridae ||Epstein-Barr virus ||Nasopharyngeal carcinoma |
| ||Burkitt lymphoma |
| ||Hodgkin disease |
| ||B-cell lymphoma |
| ||Human herpesvirus 8 ||Kaposi sarcoma |
|Hepadnaviridae ||Hepatitis B virus ||Hepatocellular carcinoma |
|Polyomaviridae ||Merkel cell virus ||Merkel cell carcinoma |
|Retroviridae ||Human T-lymphotropic virus ||Adult T-cell leukemia |
| ||Human immunodeficiency virus ||AIDS-related malignancies |
|Flaviviridae ||Hepatitis C virus ||Hepatocellular carcinoma |
Animal viruses are studied to learn how a limited amount of genetic information (one or a few viral genes) can profoundly alter the growth behavior of cells, ultimately converting a normal cell into a neoplastic one. Such studies reveal insights into growth regulation in normal cells. Tumor viruses are agents that can produce tumors when they infect appropriate animals. Many studies are done using cultured animal cells rather than intact animals, because it is possible to analyze events at cellular and subcellular levels. In such cultured cells, tumor viruses can cause “transformation.” However, animal studies are essential to studying many steps in carcinogenesis, including complex interactions between virus and host and host responses to tumor formation.
Studies with RNA tumor viruses revealed the involvement of cellular oncogenes in neoplasia; DNA tumor viruses established a role for cellular tumor suppressor genes. These discoveries revolutionized cancer biology and provided the conceptual framework for the molecular basis of carcinogenesis.
GENERAL FEATURES OF VIRAL CARCINOGENESIS
Tenets of viral carcinogenesis are summarized in Table 43-2.
TABLE 43-2Tenets of Viral Carcinogenesis |Favorite Table|Download (.pdf) TABLE 43-2 Tenets of Viral Carcinogenesis
Viruses can cause cancer in animals and humans
Tumor viruses frequently establish persistent infections in natural hosts
Host factors are important determinants of virus-induced tumorigenesis
Viruses are seldom complete carcinogens
Virus infections are more common than virus-related tumor formation
Long latent periods usually elapse between initial virus infection and tumor appearance
Viral strains may differ in oncogenic potential
Viruses may be either direct- or indirect-acting carcinogenic agents