ANALYSIS OF HPV16, HPV18, HPV31, AND HPV35 DNA IN PREINVASIVE AND INVASIVE LESIONS OF THE UTERINE CERVIX

Aims-To analyse the physical state of different human papillomavirus ( HPV) DNAs in 55 intraepithelial and invasive HPV associated cervical n eoplasms. Methods-Restriction analysis, using a panel of five HPV type specific enzymes, was carried out for each sample; this was followed by Southern blot analysis.Results-Six (25%) of 24 cervical intraepithe lial neoplasms had integrated DNA of different HPV types. In contrast, integration was detected in 25 (81%) of 31 cervical carcinomas. Tumou r samples revealed differences in the integration profile of HPV16 and the other HPV types. Six (26%) of 23 HPV16 associated cancers contain ed only episomal DNA. In contrast, all eight tumours containing HPV18, 31, or 35 revealed integrated DNA exclusively. Conclusions-The result s suggest that in advanced cervical intraepithelial neoplasia lesions, a subset of lesions can be identified in which the viral genome is in tegrated and there is a greater risk of malignant progression. In addi tion, HPV16 DNA was not present in the integrated form in 26% of tumou rs, suggesting that integration and subsequent inactivation of the tra nscriptional regulator, E2, are not essential steps for the developmen t of HPV16 associated carcinoma. In this respect, the behaviour of HPV 16 associated tumours is different from HPV18, 31, and 35 associated t umours, where the viral genome is always present in the integrated for m.