Abstract

The overall goal of this proposal is to relate the presence of human papillomavirus (HPV) to the outcome of disease - recurrence and survival - in women with invasive anogenital cancer. The study group will include women with invasive cervical or anal carcinomas of any histologic type and women with invasive squamous cell carcinoma of the vulva. This study will focus on cervical cancer as these tumors constitute the largest number of cases in this population and have the most significant world-wide public health impact. The presence of HPV DNA (or a specific genotype of HPV) will be studied in relation to the risk of death or tumor recurrence in women with cervical cancer and the risk of death in women with vulvar or anal cancer. HPV genomes will be detected and typed by polymerase chain reaction (PCR) amplification. Secondarily, the same risks will be studied in relation to seroreactivity to specific HPV antigens. The occurrence and persistence of HPV DNA in regional node metastases of cervical, vulvar and anal cancers will be studied to determine if detection of HPV DNA in nodal tissues is a marker for early metastases. All lymph nodes removed at surgery (both histologically affected and unaffected) from women with HPV DNA-positive and DNA-negative tumors will be examined using PCR amplification for detection of HPV sequences.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA042792-07
Application #
3773163
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109

  Publications

Bao, Xiao; Hanson, Aimee L; Madeleine, Margaret M et al. (2018) HLA and KIR Associations of Cervical Neoplasia. J Infect Dis 218:2006-2015
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:
Madeleine, Margaret M; Johnson, Lisa G; Doody, David R et al. (2016) Natural Antibodies to Human Papillomavirus 16 and Recurrence of Vulvar High-Grade Intraepithelial Neoplasia (VIN3). J Low Genit Tract Dis 20:257-60
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
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
Galloway, Denise A; Laimins, Laimonis A (2015) Human papillomaviruses: shared and distinct pathways for pathogenesis. Curr Opin Virol 14:87-92
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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