Human Pathogenic Papillomaviruses

The etiologic involvement of specific human papillomavirus (HPV) types in cancer of the cervix and their role in a substantial proportion of other anogenital cancers and cancers of the oropharynx (most prominently cancers of the tonsils and of the larynx) label HPV as a prime target for the analysis of mechanisms leading to the development of malignant tumors in humans. As in other viral infections linked to human cancers, HPV infection is not sufficient for the induction of malignant growth. It emerges, however, as the main factor, introducing new genes into the latently infected cells whose function as oncogenes have become clearly established during the past few years. The regulation of their expression by specific host cell proteins, stimulated by intra- and intercellular signals, seems to represent a primary defense mechanism against the induction of unrestricted growth. The failure of this host cell control system, on the other hand, by mutational changes affecting the host cell genome appears to predispose for malignant conversion. This volume summarizes various aspects of HPV research and its relationship to human cancers and provides an overview of current topics in an exciting research field.

The hypothesis that cancer of the cervix is infectious was raised more than 150 years ago (Rigoni-Stern 1842). The first cell-free transmissions of papillomas were reported 95 years ago (McFadyan and Hobday 1898). A report of cell- free trans-mission of human warts was published in 1907 (Ciuffo). Thus, since these initial discoveries papillomavirus research has had to go a long way before it became possible to link these infections to cancer of the cervix (Durst et al. 1983; Boshart et al. 1984). Table 1 lists a selection of the publications that form the basis for our present understand- ing of the role of human pathogenic papillomaviruses (H PV) in human cancers. The identification of specific H PV types in cervical cancer in 1983, 1984 and in subsequent years substantially boosted activities in papillomavirus research. In part this is because cancer of the cervix ranks first in cancer incidence in develop- ing countries and is an important cause of cancer death in affluent societies (Parkin etal. 1984; I.A.R.C. 1989). Premalignant cervical lesions, particularly in affluent soci- eties, also contribute considerably to morbidity. Moreover, the availability of cell lines harboring H PV DNA and the identification of H PV genes as oncogenes have permitted in vitro analyses of H PV genome persistence, gene expression, and gene functions.