Human herpesvirus 8 (HHV-8) : clinical and epidemiological aspects and clonality of associated tumors

HHV-8 belongs to the family I Herpesviridae, the subfamily Gammaherpesvirinae and the genus Rhadinovirus. While several viral homologs exist in both old-world and new-world non-human primates, HHV-8 I is the only known human rhadinovirus. HHV-8 is considered to be the etiological agent of the four clinical-epidemiological forms of Kaposi's sarcoma (classic, endemic, post-transplant and epidemic/HIV-associated). In several African regions, epidemic KS is the most frequently diagnosed malignancy. In 2002, the estimated annual incidence of KS worldwide was approximately 65 000 cases, representing 1% of all diagnosed cancers. HHV-8 is also associated with primary effusion lymphoma, some cases of multicentric Castleman disease, and other rare lymphomas. All these tumors mainly affect immunodeficient patients. Recent studies indicate that KS tumors are due to mono- or oligoclonal expansion of latently HHV-8-infected spindle cells, Finthermore, advanced multicentric KS lesions are of multiclonal origin. HHV-8 is not a ubiquitous virus. It is mainly endemic in areas where classical or endemic Kaposi's sarcoma is highly endemic, including the Mediterranean basin and East and Central Africa. In the latter areas, the HHV-8 seroprevalence can reach 80% in the adult population. In the homosexual population (mainly in the USA and Europe), HHV-8 is mainly transmitted during repeated sexual contacts, whereas in Africa it is mainly transmitted from mother to child and among siblings. Saliva seems to play a major role in HHV-8 transmission. Molecular epidemiology studies of the K1 gene (one of the most variable genomic regions) have revealed different molecular subtypes, at least some of which appear to be linked mainly to the geographic origin of the samples rather than to the underlying disease.