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.