Human papillomaviruses (HPVs) appear to be etiolologically related to the development of cancer of the uterine cervix. DNA of several different HPV types, including HPVs 6, 11, 16, 18, 31, and 33, have been found in condylomatous and cervical intraepithelial neoplastic (CIN) lesions, while the development of invasive carcinoma appears to be related to the presence of specific HPV types, in particular HPVs 16, 18, and 31. A subset of patients with CIN lesions recover spontaneously, whereas other patients have persistent HPV infection and lesions which may progress to invasive cancer. It is clear that host factors, other than the HPV type infecting the cervix, must play a role in determining the outcome of infection. It has been suggested that immune deficiency, either local or systemic, particularly of the cell mediated immune system, may predispose to the dissemination and progression of HPV induced lesions in man. We have identified HPVs of different types in a large group of women with CIN lesions. The availability of a group of women infected with known HPV types, and with documented clinical features, offers a unique opportunity to study immune responses to HPV-associated antigens. Identification of biologically important HPV-associated antigens will ultimately lead to the development of new diagnostic, therapeutic and preventative approaches to the management of HPV-induced disease. Our major objectives are: 1. To identify HPV-associated antigens recognized by the humoral and the cellular immune system of patients with genital infection with known HPV types, using as antigens both recombinant HPV proteins expressed in bacteria and synthetic peptides. 2. To correlate patient immune responses to specific HPV antigens with clinical status and outcome of HPV infection (i.e. regression, viral persistence and/or progression). 3. To identify and characterize antigens seen by T lymphocytes and to develop human T-cell clones reactive with these antigens as an in vitro model system to study the nature and specificity of cell-mediated responses to HPV. 4. To produce serologic reagents reactive with selected potentially type-specific HPV epitopes using synthetic peptides. To use these sera to specifically identify HPV proteins expressed in genital lesions infected with known HPV types.
