Human papillomavirus genomes in squamous cell carcinomas of the uterine cervix

The association between invasive cervical carcinoma and human papillomavirus (HPV) has now been established beyond doubt, but this is not necessarily a direct-and-effect association. To assess the causality of HPV, we analyzed HPV genomes in squamous cell carcinomas (SCCs) [corrected] of the uterine cervix by both blot hybridization and PCR. Genital HPV sequences were found in 231 (79%) of 294 SCCs by blot hybridization with more than five copies of entire HPV genomes identified in some cases including HPV 16 (92 cases), HPV 58 (32 cases), and HPV 52 (24 cases). By PCR-direct sequence analysis in 250 of 294 SCCs, genital HPV sequences were found in 240 samples (96%). The partial L1 sequences of HPV 16 were identified in 123 cases, and those of HPVs 18 and 31 were found in 24 and 20 cases, respectively. In addition, multiple HPV types were identified in 29 (12%) of 250 SCCs, and the HPV copy number, detected by PCR only, was less than 0.05. Marked discrepancies were therefore evident between the two analytical techniques. In this report, we discuss the causality of HPV for SCC with regard to the length of the viral genome, the amount of viral DNA, and multiple HPVs in single SCCs.