Human Herpesvirus 8 and Human Cancer

28 May

We have already seen the actual and potential role of herpesviruses in the causation of human cancer. EBV was among the first definitive human cancer-causing viruses, and the herpes sim- plex group has been suggested  but not proven to have a role in the development  of cervical cancer in the human. In 1994 Chang et al. demonstrated the presence of a human herpesvirus, now termed HHV-8 or Kaposi sarcoma–associated  herpesvirus (KSHV), in all epidemiological forms of Kaposi sarcoma, an angiosarcoma found worldwide but most recently at an extremely high incidence in AIDS patients, which is 7000 times higher than in the non-AIDS population (Emmanoulides et al., 1996). HHV-8 genomes have also been consistently found in primary ef- fusion lymphoma (PEL) and multicentric Castleman disease (MCD). Originally, PEL was con- fused  with  the form  of Burkitt  lymphoma  seen  in western  nations,  involving  primarily

Figure 12.17 Age-specific  incidence of cervical, vulvar, anal, and penile cancer in the Danish popula- tion. (After Melbye and Frisch, 1998, with permission of the authors and publisher.)

abdominal  lymphoid  structures.  However,  closer investigation  revealed  clear differences  be- tween the two and particularly in the viral genomes involved. The virus has also been found in several benign and malignant endothelial lesions in patients with Kaposi’s sarcoma (Dictor et al., 1996). In addition, in other studies the presence of HHV-8 sequences was seen in premalig- nant Bowen disease (71.4%) and malignant squamous cell carcinoma (50%), as well as in 33.3% of actinic keratoses (Inagi et al., 1996). In addition, McDonagh et al. (1996) reported the pres- ence of HHV-8 sequences in 29% of angiosarcomas in patients, most of whom were not immu- nocompromised.  Transmission  of HHV-8  in AIDS patients  appears  to be largely by sexual means. However, in Africa, both horizontal and vertical transmission of HHV-8 is quite common among young children (cf. Schulz, 1999). Although the presence of the virus in Kaposi sarcoma, PEL, and MCD argues very strongly that there is a causative association between infection and the neoplastic transformation, other data are also supportive of this argument. Flore et al. (1998) demonstrated the transformation of primary human endothelial cells by HHV-8 in vitro. In addi- tion, the relationship of the presence of antibodies to HHV-8–associated  latent nuclear antigens (see below) in relation to the development of Kaposi sarcoma strongly indicates a direct caus- ative relationship (Figure 12.18).

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