) Among neoplastic diseases associated with HIV infection in women are HPV-associated carcinomas of the uterine cervix, as well as premalignant squamous intraepithelial lesions (SIL). Risk factors in normal women for persistent or progressive SIL include persistent infection with high risk HPVs, high viral load, increased age, infection with other sexually transmitted diseases, cigarette smoking, and HLA type. HIV seropositivity in women with low CD4 counts has been associated with an increased prevalence of HPV infection, high viral load, increased rate of persistent infection as well as an increased rate of SIL suggesting that HIV-related immunosuppression increases the risk of chronic HPV infection. Whether cervical HPV infection and SIL progress more rapidly in HIV seropositive immunosuppressed women is controversial. Whether these effects are due to deficient CMI responses to HPV, which are independent of CD4 counts, or other factors has yet to be determined. Whether HLA class II haplotypes, which have been associated with susceptibility or resistance to cervical cancer in an HPV type-specific manner, play a role in the natural history of HPV-induced SIL in immunosuppressed patients is unclear. The applicant proposes to prospectively study the role of cell-mediated immune (CMI) responses to HPV in a cohort of high risk female intravenous drug-users who are either HIV-positive or HIV-negative. The major specific aims are: 1) To examine the association between CMI responses to HPV16 E6, E7 and E4 peptides and outcome of HPV infection and HPV-induced disease in HIV+ and HIV- women. Assays used will include lymphoproliferative CMI assays and assessment of cytokine gene expression by activated peripheral blood mononuclear cells (PBMC). 2) To identify risk factors for absence of CMI responses to HPV16 peptides and deficient general CMI status in HIV+ and HIV- women. Risk factors include: a) HIV serostatus; b) CD4 counts and CD4 percent; HLA class II haplotypes; HPV infection (presence, type, viral load); and epidemiologic factors (e.g., sexual activities, past history of STD or genital warts). 3) To examine whether the effect of CMI responses on outcome of HPV infection and HPV-induced disease (aim 1) and the association between HLA and CMI response (aim 2) are dependent on HIV serostatus or extent of HIV-related immunosuppression.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA073586-01
Application #
2011601
Study Section
Special Emphasis Panel (SRC (C2))
Project Start
1996-09-30
Project End
2001-07-31
Budget Start
1996-09-30
Budget End
1997-07-31
Support Year
1
Fiscal Year
1996
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Pathology
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461