The overall goal of this project is to characterize the immune response to HPV infection of the genital tract and to define the role of immune modulation in the progression to malignancy. Serological assays to detect serum IgG antibodies to HPV types 6, 16 and 18 have been developed and form the basis for a new marker of HPV exposure in epidemiologic studies.
The specific aims of this study are: 1) To continue characterizing the humoral immune response in greater depth by examining the contribution of antibodies directed against conformational epitopes using yeast expressed proteins and virions made using recombinant vaccinia virus vectors; and continuing to delineate immunoreactive epitopes; 2) To examine HPV specific IgA antibodies present in serum, saliva, and cervicovaginal secretions; 3) To compare the Western blot assay with ELISAs using yeast expressed proteins, virions, or synthetic peptides for screening methods; 4) Populations will be screened for HPV antibodies to determine a) the prevalence of antibodies in the general population and in cases with anogenital cancer; b) immunological markers associated with malignancy; c) risk factors associated with seropositivity; d) the correlation between HPV antibodies and other measures of infection; and 5) To study the cell mediated immune response to HPV infection in lymphoproliferative assays and by identifying cytotoxic T cells. Information about the immune response to HPV infection is essential in epidemiologic studies, in the clinical management of disease, and in the development of vaccines to prevent infection or tumor development.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA042792-07
Application #
3773160
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Leo, Paul J; Madeleine, Margaret M; Wang, Sophia et al. (2017) Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study. PLoS Genet 13:e1006866
Wallace, Nicholas A; Khanal, Sujita; Robinson, Kristin L et al. (2017) High-Risk Alphapapillomavirus Oncogenes Impair the Homologous Recombination Pathway. J Virol 91:
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Wallace, Nicholas A; Robinson, Kristin; Howie, Heather L et al. (2015) ?-HPV 5 and 8 E6 disrupt homology dependent double strand break repair by attenuating BRCA1 and BRCA2 expression and foci formation. PLoS Pathog 11:e1004687
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Hardikar, Sheetal; Johnson, Lisa G; Malkki, Mari et al. (2015) A population-based case-control study of genetic variation in cytokine genes associated with risk of cervical and vulvar cancers. Gynecol Oncol 139:90-6
Safaeian, Mahboobeh; Johnson, Lisa G; Yu, Kai et al. (2014) Human Leukocyte Antigen Class I and II Alleles and Cervical Adenocarcinoma. Front Oncol 4:119
Madeleine, Margaret M; Carter, Joseph J; Johnson, Lisa G et al. (2014) Risk of squamous cell skin cancer after organ transplant associated with antibodies to cutaneous papillomaviruses, polyomaviruses, and TMC6/8 (EVER1/2) variants. Cancer Med 3:1440-7
Wallace, Nicholas A; Galloway, Denise A (2014) Manipulation of cellular DNA damage repair machinery facilitates propagation of human papillomaviruses. Semin Cancer Biol 26:30-42

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