Human Papilloma Virus (HPV) type 16 infection is associated with cervical intra-epithelial neoplasia (CIN) and invasive carcinoma. By analogy with other papilloma viruses, the HPV E6, E7 and E5 open reading frames (ORF) may be particularly significant for the pathogenesis of cervical cancer. The long term objectives of this work are to understand the role of the HPV 16, E6, E7 and E5 ORFs in the development of cervical cancer; to correlate the natural history of cervical neoplasia and the expression of these ORFs; to develop assays for the corresponding gene products in cervical tissue that might be useful diagnostically, prognostically and to monitor the results of therapy; and to provide a rationale for the possible development of an E6, E7 and E5 ORF specific vaccine for the prevention or control of cervical neoplasia. The specific objective of this proposal is to determine if the E6, E7, and E5 ORFs of HPV 16 are expressed in CIN and invasive carcinoma. Reagents will be prepared to detect transcripts from these ORFs and their corresponding proteins in HPV 16 infected, cytologically characterized, cervical specimens that have been collected from women followed prospectively in three dysplasia clinics. E6, E7 and E5 transcriptional activity will be sought in these specimens by RNA in situ hybridization with ORF specific molecular probes consisting of RNA transcripts sub-cloned DNA fragments in PSP18. Proteins encoded by the E6, E7 and E5 ORFs will be detected with antibodies elicited by synthetic peptides corresponding to HPV 16 type-specific regions of these ORFs. These antisera will be used to study clinical specimens by Western blotting, immuno-precipitation, and immunohistochemistry.
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