GENETIC-CHARACTERIZATION OF THE HUMAN PAPILLOMAVIRUS (HPV) 18-E2 GENEIN CLINICAL SPECIMENS SUGGESTS THE PRESENCE OF A SUBTYPE WITH DECREASED ONCOGENIC POTENTIAL

HPV 18 is associated with 2 divergent phenotypes: (ii aggressive cervi cal cancer and a preponderance of cancer relative to cervical intra-ep ithelial neoplasia (GIN) and (ii) benign warty lesions of the cervix. The E2 gene of HPV 18 encodes a regulatory protein that represses vira l oncogene transcription and is involved in viral replication. Variati on within the E2 gene of HPV 18 and its correlation with the morpholog ic grade of associated lesions were analyzed in a sample of 20 HPV 18- positive cervical specimens representing a spectrum of pathology from low-grade CIN to cervical cancer. An amplifiable HPV 18 E2 gene was pr esent in 3 of 5 cancers, indicating that E2 disruption was not require d far cancer development. Single-strand conformation polymorphism and PCR analyses revealed a high degree of polymorphism throughout the E2 gene. Direct DNA sequencing of both strands of a 154-bp fragment revea led a variability of 5.8%. Six intra-epithelial lesions contained alte rations in common that account for 3.9% of the variation and appear to constitute a subtype. Within the 154-bp region, 2 of 3 cervical cance rs and 0 of 12 intra-epithelial lesions were identical to the publishe d HPV 18 sequence. DNA sequence analysis of a region extending into th e E5 open reading frame revealed deletions in the E2/E5 intragenic reg ion that were present in 50% of the members of the subtype. Our data d emonstrate significant sequence variation within the E2 gene and sugge st the presence of an HPV 18 subtype with decreased oncogenic potentia l. (C) 1995 Wiley-Liss, Inc.