To prove a causal relationship between a putative cancer-causing virus and human cancer is not a
simple task. Such proof relies on evidence that is to a fair extent circumstantial. This evidence includes
(1) epidemiological data showing a correlation between living in an area of endemic viral infection and a type of cancer; (2) serological evidence of antibody titers to viral antigens in patients with a given cancer type; (3) evidence for insertion of viral DNA into a cancer-bearing host’s cell genome; (4) evidence for a consistent chromosomal translocation, particularly those involving an oncogene, in virally infected patients; (5) data showing that viral infection of cells in culture or transfection of viral genes into cells
causes cell transformation and the ability of such cells to produce tumors in nude mice; and (6)
development of cancers of the suspected target organ in transgenic mice produced by embryonic
gene transfer of viral genes.
On the basis of this sort of evidence, some human cancers are considered to be caused by viral infection either directly or indirectly. By ‘‘directly,’’ I mean that the viral gene(s) can themselves cause cells to become malignant (sometimes also requiring the loss of a tumor suppressor gene). By ‘‘indirectly,’’ I mean that viral infection may simply cause the progression of malignant cell growth by producing an
immunodeficiency state (e.g., the occurrence of non-Hodgkin’s lymphoma in HIV-infected patients)
or by stimulating the proliferation of already transformed cells. Sometimes viral infection acts in concert with other infectious agents or chemical carcinogens. Such is the case for malarial infection of Epstein-Barr virus (EBV)– infected patients and for aflatoxin exposure of individuals bearing the hepatitis B viral genome in their liver cells (see below). The types of human cancer thought to be caused by viral
infection and the strength of epidemiological associations Epstein-Barr virus has been linked to four different types of human cancer: Burkitt’s lymphoma (BL), nasopharyngeal carcinoma (NPC),
B-cell lymphomas in immunosuppressed individuals such as HIV-infected patients, and some
cases of Hodgkin’s lymphoma.149 The evidence is strongest for an association with BL and NPC.
Infection with EBV does not by itself cause cancer. On average, across the world, about 90% of the population may be infected by the time they reach adulthood.
In some endemic areas, the incidence rate approaches 100%. In developing countries, EBV infection often occurs in young childhood. In more affluent societies, EBV infection tends to occur as the ‘‘kissing age’’ of adolescence or young adulthood is reached, and manifests itself as infectious mononucleosis.
In developing countries, particularly in equatorial Africa, concomitant or subsequent infection with the malarial parasite induces B-cell proliferation and an immunodeficiency state that leads to malignant transformation and progression. There is a consistent chromosomal translocation involving immunoglobulin genes, usually on chromosome 14, and sequences within or adjacent to the c-myc gene locus on chromosome. The role of EBV in NPC is less well characterized, but the evidence for an association includes high serum antibody titers against EBV antigens and the presence of EBV DNA in NPC cells. Similar evidence suggests an association between EBV infection and induction of some
B-cell lymphomas and some Hodgkin’s disease cases in immunosuppressed individuals, although
the exact role of EBV remains to be elucidated.
