The molecular biology of human papillomaviruses and the pathogenesis of genital papillomas and neoplasms.

Numerous studies over the past several years have demonstrated that human papillomaviruses (HPV) may play a significant role in the development of several types of human neoplasia. Although it has been accepted for some time that HPVs are responsible for benign epithelial tumors, data accumulated in more recent years have implicated this group of animal viruses in a number of premalignant lesions, as well as a variety of epithelially derived malignancies. Genital, oral, and some rare types of cutaneous cancers have all been found to contain varying degrees of HPV DNA. In several instances secondary tumors resulting from metastases to lymph nodes and lungs have also been demonstrated to contain HPV DNA. Although there is a strong correlation between the presence of the virus and the malignant phenotype in several of these cancers, the precise role of the virus in the development of malignant tumors has not yet been elucidated. A major difficulty in elucidating the role of papillomaviruses in oncogenesis has been the lack of an appropriate in vitro culture system that would permit the growth of the virus and allow an analysis of its transforming properties. Nevertheless, recent advances in molecular biology have permitted the molecular cloning and amplification of HPV viral DNA, thereby facilitating its use as a probe for the detection of miniscule amounts of HPV DNA and HPV RNA in tumor biopsies. Moreover, DNA transfections of cells in culture have been extremely useful in the study of viral DNA replication and transformation properties, providing information on the maintenance and oncogenicity of HPV DNA. These advances have implications for the improved detection of HPV infections, which will aid in patient diagnosis and prognosis. In addition, future treatment and prevention programs may come as a direct result of these basic studies on the mechanism of HPV-induced oncogenesis.