Genome amplification of human papillomavirus types 16 and 18 in cervical carcinomas is related to the retention of E1/E2 genes

Abstract

The level of amplification (copy number/cell) of HPV16 and HPV18 viral genomes and its correlation with the presence of E1/E2 genes were analyzed in a sample of 42 HPV16- and 21 HPV18-positive cervical carcinomas of different clinical stages and histological types. The viral copy number/cell was assessed by dot-blot hybridization and the presence of E1/E2 genes by PCR and Southern blot. The copy number/cell was significantly lower in HPV18-positive than in HPV16-positive tumours (23 +/- 8 and 457 +/- 191 respectively). Nearly half of the HPV16s (43%) were distributed similarly to the HPV18s in the ranges of 50 or less copies, having its peak at the group of 1 to 10 copies, whereas the remaining HPV16s (57%) spread over the groups of 51 or more copies, with another peak at the group of 101 to 500. The E1/E2 region was absent in all tumours positive for HPV18 and present in 64% of those positive for HPV16. The HPV16 tumours negative for E1/E2 had a much lower viral copy number (17 +/- 12) than the positive ones (582 +/- 212), thus resembling HPV18-positive tumours. Viral copy number was negatively correlated with the clinical stage of the tumours and directly associated with the degree of histological differentiation. However, these correlations are primarily attributable to the presence or absence of an intact E1/E2 region.