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Kaposi’s sarcoma

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Epidemic Kaposi's sarcoma, linked to HIV / AIDS, is one of the most common cancers in Central and South Africa

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Different forms

Kaposi’s sarcoma was described in the late 19th century as a highly rare chronic disease that caused skin tumors, especially in the extremities, in elderly individuals, mostly men, around the Mediterranean Basin (classic Kaposi’s sarcoma). In around 1950, it was observed in East Africa, around the African Great Lakes region, where it emerged as an endemic form of cancer that also occurred, although rarely, in children and young adults. This form is more severe and sometimes diffuse, affecting the lymph nodes and viscera. A third form of Kaposi’s sarcoma was then described in transplant patients treated with immunosuppressive drugs (transplant-related Kaposi’s sarcoma). Since the emergence of the AIDS epidemic, an epidemic form of Kaposi’s sarcoma has been associated with HIV infection, and this is currently the predominant form. The lesions are often diffuse and occur on the skin and in the viscera. In Western countries, KS is rare among heterosexuals and drug users; it mainly affects HIV-positive male homosexuals or bisexuals. Epidemic HIV-associated KS is currently one of the most frequent types of cancer in Central and South Africa (from 10 to nearly 50% of cancer cases diagnosed in some regions), and it affects both men and women. The rapid rise in this form is linked with the spread of HIV in a population where HHV-8 is highly endemic.

An infectious disease ?

The theory that Kaposi’s sarcoma may be caused by a virus was raised in the early 1970s. The discovery of viral DNA sequences in the skin lesions of HIV-infected patients in 1994 confirmed that human herpesvirus-8 (HHV-8) is associated with Kaposi’s sarcoma. Since then the virus has been fully sequenced.

The virus has been found in tumor lesions of all known forms of KS. It has also been demonstrated that HHV-8 infection precedes the emergence of the disease: seroconversion for HHV-8 and detection of viral sequences in peripheral blood lymphocytes a few months or years before the emergence of the clinical disease. The level of prevalence of HHV-8 antibodies in adults (0 to 5% in the UK, 20% in southern Italy and 75% in Uganda) corresponds with the incidence of Kaposi’s sarcoma. These arguments, associated with molecular data, have implicated HHV-8 as the causal agent of Kaposi’s sarcoma.

Pathogenesis

Much still remains unknown about the pathogenesis of Kaposi’s sarcoma. While we know that the virus plays an essential role, its interaction with the immune system, especially the inflammatory cytokines, remains poorly understood. And little is known about exactly how KS spreads: what is the precise origin of the tumor cells, are the lesions really cancerous, does the disease involve clonal proliferation (i.e. is it derived from a single cell)?

Transmission

The epidemiology and transmission mechanisms of HHV-8 remain poorly understood. Although the virus is transmitted during sexual contact among the male homosexual population, in highly endemic areas in Africa it mainly seems to spread through mother-to-child or child-to-child transmission, primarily by saliva, which seems to be one of the reservoirs of the virus. Heterosexual transmission appears to be rarer in endemic areas.

The existence of several asymptomatic carriers also raises the problem of screening for the virus in blood donations and especially organ donations.

Other diseases caused by HHV-8

HHV-8 is associated with at least two other diseases: a specific type of rare lymphoma, primary effusion lymphoma (PEL, also known as body cavity lymphoma), which mainly affects people infected with HIV, and some forms of an equally rare disease, multicentric Castleman disease. Other rare lymphoid proliferations have also been associated with the virus.

At the Institut Pasteur

The Oncogenic Virus Epidemiology and Pathophysiology Unit, led by Antoine Gessain, is investigating the transmission mechanisms of HHV-8 in highly endemic areas, in collaboration with the Institut Pasteur International Network, and is also carrying out research into the genetic variability of the virus and the viral and cellular clonality of associated tumors.

The teams involved at the Institut Pasteur

Oncogenic Virus Epidemiology and Pathophysiology Unit, led by Antoine Gessain


Janvier 2019  



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