Herpes Simplex Viruses and Human Cancer

28 May

In 1972 a report by Frenkel et al. (1972) demonstrated the presence of a portion of herpes sim- plex II viral DNA within a human cervical neoplasm. Since that time, a number of investigations have demonstrated the presence of fragments of the herpes simplex genome within human geni- tal neoplasms  (Macnab, 1987), but the significance  of such findings in the genesis of human genital neoplasia is not clear, especially in view of the demonstrated importance of the human papilloma virus in the development  of such neoplasms (see below). Transfection  experiments both in vivo (Anthony et al., 1989) and in vitro (DiPaolo et al., 1990) have demonstrated  the oncogenic potential of herpes simplex DNA in lower animals, but epidemiologic  studies have not indicated that a direct causal association between herpes simplex virus infection and genital cancer occurs in the human (Melnick et al., 1976; Graham et al., 1982). Somewhat  more re- cently, Di Luca et al. (1995) have proposed that herpes simplex virus may function as a “cooper-

Figure 12.15 Diagram  of the natural history of HBV infection  leading to chronic hepatitis,  cirrhosis, and hepatocellular  carcinoma  (HCC). Possible interventions  are noted at the top of the figure. Note that while HBV replication  occurs early in the disease,  integration  into DNA and the potential  for genomic instability  occur in parallel with the development  of HCC. (Adapted from di Bisceglie et al., 1988, with permission of the authors and publisher.)

ating agent” in the development of human genital neoplasia. The virus might act as an initiator or a progressor or even to alter cellular and viral gene expression. As yet, however, these con- cepts are somewhat theoretical, and the actual role, if any, that herpes simplex virus infection may play in the development of human genital cancer is not clear.

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