Certain types of human papilloma viruses (HPV) are associated with human genital proliferative diseases, and among them HPV16 and HPV18 seem to play an important role in the occurrence of cervical cancer. We used restriction enzyme analysis and molecular hybridization, in order to investigate the type of viral infection and the physical state of viral DNA in gynecological benign, pre-malignant and malignant lesions. HPV6/11 specific sequences could only be detected as episomes and this in benign lesions classified as condylomata acuminata. On the other hand, HPV16 and HPV18 sequences were detected in non-malignant lesions such as flat condylomata (7 out of 14 cases), pre-malignant lesions including cervical intra-epithelial neoplasias (10 out of 20 cases), and most frequently in cervical invasive cancers (21 out of 27 cases). In a large number of virus-positive cases, HPV16 and HPV18 could only be discerned in forms consistent with the existence of episomes and/or randomly integrated head-to-tail oligomers. However, some invasive carcinomas and cervical intra-epithelial neoplasias contained, in addition, clonal outgrowths with detectable virus-cellular junction fragments of the integrated viral genomes. In the light of these data, monitoring the type of viral infection proves to be an important adjunct to histological analysis when assessing those patients affected by condyloma or cervical intra-epithelial neoplasia who are at risk for developing invasive carcinoma.
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