Human papillomaviruses and carcinomas.
The recognition of multiple types of human papillomaviruses has resulted in remarkable progress in the detection of persisting viral nucleic acid sequences in carcinomas. The consistent transcription in tumors of two early open reading frames, E6 and E7, with few exceptions (Lehn et al., 1985), indicates a role for the products of these genes in the induction and/or maintenance of the transformed state. A number of studies have shown that in vitro transformation can be achieved by transfection of E6/E7 DNA, and proteins encoded by these DNA sequences can be demonstrated in primary human keratinocytes immortalized by this DNA (Kaur et al., 1989). Mutagenesis experiments are needed to determine the absolute requirement for and function of these genes in transformation. A preferential association of some types with benign lesions while others may be frequently found in malignant tumors has been observed. HPV types 5 and 8 in epidermodysplasia verruciformis patients and types 16, 18, 31, 33, etc. in genital lesions are most frequently associated with progression to malignancy, whereas other types, such as HPV-6,-10, -11, and -20, are regularly identified in benign warts. Such distinctions are not absolute but provide the initial steps toward establishing a causal role for some human papillomaviruses in carcinomas. The need for well-designed epidemiological studies in concert with optimum molecular and serologic evaluations is evident (Armstrong et al., 1988). The data from human and animal studies indicate that papillomaviruses contribute significantly to the development of many, if not all, carcinomas, but we do not yet have a clear understanding of the importance of other interacting viral, chemical, or cellular factors. The application of gene cloning and non-stringent hybridization (Law et al., 1979) has provided us with an apparently ever-increasing catalog of human papillomaviruses. More effort is now required to establish their prevalence, the natural history of infection, and the mechanism of neoplastic transformation.
Galloway
D A
DA
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
McDougall
J K
JK
D000818:Animals; D002277:Carcinoma / Q000382:microbiology*; D002472:Cell Transformation, Viral; D006801:Humans; D009369:Neoplasms / Q000382:microbiology*; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D014412:Tumor Virus Infections / Q000382:microbiology*