Human papillomavirus-16 and genital cancer: are tests for the viral gene expression in vitro indicators for risk factors in vivo?

Abstract

Human papillomaviruses are found in up to 90% of all cervical carcinomas and are considered to play a causal role in the etiology of this malignancy. The genome of human papillomaviruses consists of a single circular DNA molecule with a size of approximately 8000 basepairs. 90% of this genome encodes proteins involved in functions such as neoplastic transformation of the host cell or formation of the viral capsid. The remaining 10% of the genome, which is termed upstream regulatory region (URR), harbours elements to control expression of the viral genes. We have identified in the URR DNA elements that regulate viral gene expression in the presence of glucocorticoid hormones or tumour promoting substances. This was done by DNase I protection experiments and functional analysis of fusion genes. Our data predict that the transforming potential of the virus might be stimulated by certain steroid hormones, polypeptide hormones and tumour promoting chemicals.