Natural History of HPV-Infection to Neoplasia

Anna-Barbara B. Moscicki, M.D.
University of California at San Francisco
Department of Pediatrics San
Francisco, Calif.
Funded since 1990

The long-term goal of this research project is to better understand local and systemic immune responses to human papillomavirus (HPV)infection in its natural setting of the cervix early in its course, as well as in states of persistence or clearance.

The first aim of the study is to examine the local immune response in the natural history of cervical HPV infection in young women by comparing changes in the local cervical cytokine milieu, specifically interferon (IFN)-gamma, interleukin (IL)-12, IL-10, and IL-4, in association with:

• persistence,
• clearance of initial and/or secondary infections, and
• development of squamous intraepithelial lesions.

The second aim is to examine systemic response to HPV, specifically cytotoxic T-cell response to HPV 16 infections in association with the four HPV states described above.

Four groups of women are being recruited for the study:

• women with a long history of persistent HPV infection,
• women with secondary HPV type infections,
• adolescent and young women with evidence of initial HPV infection, and
• women with a long history of persistent HPV negativity (control group).

Examinations for women from the first three groups seen every four months will include samples for: HPV DNA, cytology, cervical cell cytokine analysis using RT-PCR, C. trachomatis, N. gonorrhea, herpes simplex virus, bacterial vaginosis, and peripheral blood cytotoxic T-lymphocyte assays on women with HPV 16 infection. The control group (HPV negative) will have similar examinations every six months and have HPV serology to virus-like particles to characterize HPV exposure not defined by repeated HPV testing.

Understanding of both local and systemic immune responses to initial and subsequent HPV infections may be key in vaccine or therapeutic developments.