GENOME AMPLIFICATION OF HUMAN PAPILLOMAVIRUS TYPES 16 AND 18 IN CERVICAL CARCINOMAS IS RELATED TO THE RETENTION OF E1 E2 GENES/

The level of amplification (copy number/cell) of HPV16 and HPV18 viral genomes and its correlation with the presence of E1/E2 genes were ana lyzed in a sample of 42 HPV16- and 21 HPV18-positive cervical carcinom as of different clinical stages and histological types. The viral copy number/cell was assessed by dot-blot hybridization and the presence o f E1/E2 genes by PCR and Southern blot. The copy number/cell was signi ficantly lower in HPV18-positive than in HPV16-positive tumours (23 +/ - 8 and 457 +/- 191 respectively). Nearly half of the HPV16s (43%) wer e distributed similarly to the HPV18s int he ranges of 50 or less copi es, having its peak at the group of 1 to 10 copies, whereas the remain ing HPV16s (57%) spread over the groups of 51 or more copies, with ano ther peak at the group of 101 to 500. The E1/E2 region was absent in a ll 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 co py number (17 +/- 12) than the positive ones (582 +/- 212), thus resem bling HPV18-positive tumours. Viral copy number was negatively correla ted with the clinical stage of the tumours and directly associated wit h the degree of histological differentiation. However, these correlati ons are primarily attributable to the presence or absence of an intact E1/E2 region. (C) 1994 Wiley-Liss, Inc.