UNIFORM DELETIONS OF HPV-16 DNA IN THE CASKI CELL-LINE AND IN CERVICAL CARCINOMAS - AN ANALYSIS OF THE CHARACTERISTICS OF INTEGRATED MULTIMERIC HPV-16 GENOMES

Backgrounds - Human papillomavirus type 16 (HPV 16) has been implicate d in the development of cervical cancer for a long time. Although it i s one of the most prevalent viruses infecting the female genital tract , only a small percentage of those infected develop cancer. This paper aims to investigate possible changes in HPV 16 which might initiate n eoplastic changes. Methods and results - We have analysed the characte ristics of human papillomavirus type 16 (HPV 16) from 11 cervical carc inoma specimens and from the CaSki cell line. We have shown with PCR a mplification the presence of full length (3.8 kb) and 5 (3.0 kb, 2.7 k b, 1.5 kb, 0.8 kb, 0.5 kb) interrupted HPV 16 fragments in SCC biopsie s and the CaSki cell line revealing remarkable similarity in the proce ss of deletion in combination with integration of the HPV 16 DNA into the human genome. All the samples analysed (11) expressed integrated H PV 16. The amplification products were mapped using subgenomic oligopr obes identifying the deletions in the E1-L2 ORFs of the HPV 16 genome but invariably retaining E7 ORF. In the CaSki cell line the presence o f several inverted, and strand switched HPV 16 sequences were detected . Two HPV 16 fragments (0.8 kb, 0.5 kb), which had a large part of El and the total of E2 ORFs deleted, were present in all of the squamous cell carcinomas and the CaSki cell line. Conclusions - These prelimina ry results suggest that the retention and possibly unspliced expressio n of particular viral DNA rearrangements may be more important in the development of cervical carcinomas than others. In addition the appear ance of a characteristic pattern in the deletions might suggest the pr esence of favored sites for recombination in HPV 16 and therefore the integration and deletion of HPV 16 may not be random.