Viruses are the second most important risk factor in the onset of cancer, after consumption of tobacco products. They are implicated in 15 % of human cancers. Oncogenic viruses, in humans, are incapable of provoking the carcinogenic process by themselves and also act in association with other co-factors to render a cell malignant. It is thought that viruses are generally involved in the precursor stage of carcinogenesis. Genetic, immunological or environmental factors furnish the mutation necessary for tumor growth. The infected cell becomes malignant following a series of succeeding events, over a period ranging from a few years to a few decades.

HPV (Human papilloma Virus) :

Originating from the family of Papovaviridae, the virus is prevalent and promotes common warts on the skin and genital papillomas and is also implicated in the developement of dysplasia and cancers of the female genital tract. There are about a hundred subtypes of human papilloma virus. This virus specifically targets keratinized cells and replicates in the basal layer of squamous and glandular epithelium. They stimulate the cellular proliferation and modify the differentiation provoking the presence of warts. Only certain subtypes are associated with cancers namely 16,18,31,33 and 35. Cancers in the female genital tract arise most exclusively at the squamo-columnar junction, also referred to as the transformation zone (see diagram).

80 to 90 % of the cancers arising in the female genital tract have the integrated genes of HPV. The viral oncogene E6 and E7 combine with the oncosuppressor of the cell and litterally renders them inactive. With regards to the high risk HPV, the whole process occurs as if the infected cells are not aware that a resting phase is necessary during cell division in order that genetic mutations are repaired and restore the proper genetic code, the cell possessed before division. The accumulation of genetic errors in the latency phase of cellular division can favor the precancerous process and ultimately lead to cancer, if no other factors stop the progression.

The frequency of infection by the papillomavirus in relation to the rarity of cancers, demonstrates that this infection is not the only cause of the malignant transformation. Other factors play a role, as well. In effect, it is rare that women infected by the oncogenic papillomavirus, will have lesions that develop into cervical cancers. In many cases the immunological system contributes to a spontaneous regression, so that a mild dysplasia and at times a moderate dysplasia can revert to normal.

HBV (Hepatitis B Virus) :

Hepatocellular carcinoma is one of the most prevalent cancers in the world. It occurs more often in men that women and with the highest rate of incidence occuring in individuals between ages 30 and 50. HBV is reponsible for 80 % of the hepatocellular carcinomas in the world.These viruses from the Hepadnaviridae family are transmitted at the perinatal stage in endemic regions. Geographically , it is found mostly in China, in South East Asia and in sub-Sahara regions of Africa. Hepatitis B infection occurs at the early age but many years pass between the onset of infection and the development of hepatocellular carcinoma. In certain regions of Africa where there is a high incidence of liver cancer, aflatoxin (Aspergillus flavus) a mold which develops on grain poorly stored in humid conditions, is known as an important contributing factor.

Hepatits B is also transmitted by blood and by sexual relations. The correlation between HBV infection and hepatocellular carcinoma is well established. This virus produces a protein which encapsulates the p53 and prevents it from acting normally. The aflatoxin mutates the p53 and replaces the bases. Individuals suffering from chronic hepatits B, especially those afflicted with cirrhosis, are at a greater risk of developing hepatocellular cercinoma. This is a result of repeated cellular infections in response to which there is increased cellular divison of hepatocytes, thus resulting in a greater risk of mutations. The HCV virus, of the Flaviviridae family, is also associated with hepatocellular carcinoma

HHV4 (Human Herpes Virus 4) :
or EBV (Epstein-Barr virus)

This virus of the Herpesviridae has a double affinity for B lymphocytes and epithelial cells. Transmitted by saliva, at least 90% of individuals are infected for life. Most of the time this infection is not evident but among young adults it sometimes manifests itself as mononucleosis. The lymphocytosis, associated with infectious mononucleosis, is a result of the increased circulating atypical T cells, also known as Downey cells.

The EBV virus infects and multiplies in the epithelial cells of the oralpharynx and attacks the B lymphocytes. Immunosuppressed individuals such as HIV+, transplant patients and those with certain congenital deficiencies all have a greater risk of developing lymphatic disease caused by the EBV virus. In the absence of the proper immune response by the T cell lymphocytes, the virus provokes the multiplication of the B cell lymphocytes which are normally inactive. One of the most common consequences of the EBV infection in transplanted patients is the appearance of a lympho-proliferative disorder or a neoplastic abnormality of the smooth muscle tissue.

The EBV virus is also associated with the development of immunoblastic lymphoma, B cell lymphoma, certain types of T cell lymphoma and Hodgkin`s disease. In South East Asia it is associated with nasopharyngeal carcinoma (squamous cell carcinoma). It is also implicated in Burkitt's lymphoma, malignant tumours of the lymphatic tissues of children from central and eastern Africa and in many cases EB virus is also associated with HIV+ and malaria. It appears that EBV virus is present in half of all cancers of breast particularly those with the worse prognosis.The HHV8 or KSHV viruses associated with Kaposi sarcoma and certain types of B cell lymphomas, appear to be sexually transmitted in seropositive HIV individuals.

Human T cell Leukemia Virus (HTLV1) :

Viruses of the Retroviridae family are found in a higher porportion in endemic areas among populations in having evolved in isolation for long periods of time such as in the islands of Southern Japan, Gabon, Zaïre, Columbia, French Guiana, Surinam, the Carribeans, North East Iran and Malasia. It is transmitted by breast feeding, sexual contact and by blood. Only a small proportion of the infected persons will develop a pathology. The HTLV1 virus plays a role in the proliferation of the T cells. The presence of other genetic events is necessary for the development of a ATLL (lymphoid proliferation of malignant T cells in adults). In Japan, we also find neurological disease i.e. chronic neuromyelitis affecting the spinal cord, tropical spastic paraparesis.

 

 
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Dernière mise à jour: le 30 janvier, 2005
    
 

Pour en savoir plus:

http://www.baclesse.fr/cours/fondamentale/7-carcino-virale/Virale-0.htm carcinogenèse virale

http://www.john-libbey-eurotext.fr/articles/vir/2/5/347-54/ de l'interaction avec les protéines virales à la pathogénie des cancers humains

http://www.cdc.gov/ncidod/diseases/ebv.htm about EBV

http://www.nums.nwu.edu/igp/facindex/AiyarA.html Replication and transcriptional regulation of EBV during latency

http://www.kcom.edu/faculty/chamberlain/Website/lectures/lecture/mono.htm Infectious mononucleosis