The overall objective of this project is to improve the biologic understanding of adenocarcinoma and adenosquamous cancer of the cervix uteri (in the following referred to as adenocarcinoma) through investigation of its viral etiology, and genes encoding certain human leukocyte antigen (HLA) haplotypes. The long-term objective is to propose rational prevention strategies for this disease. Our main specific aims are to: 1) estimate the relative risks for adenocarcinoma both as a function of HPV presence overall and as a function of time since first detected infection with human papillomavirus (HPV); 2) to assess whether persistence and/or a high initial HPV 16/18/45 viral load is a determinant of adenocarcinoma; 3) to assess whether certain HLA haplotypes are associated with risk for adenocarcinoma, and if the association is mediated via a higher viral load and/or persistence of HPV 16/18/45. This project will build on experience from two previous studies examining squamous cell cervical cancer and HPV (both funded by NIH). Our capacity to conduct these studies is derived from the utilization of unique prerequisites in Sweden, namely the extensive documentation present in computerized registers for population-based PAP-smear screening, potential ascertainment of all incident cases of adenocarcinoma, and access to archival smears and tissue specimens. Using a nested case-control design in this large study base, with up to 32 years of complete follow-up, 511 women with adenocarcinoma and 511 individually matched control women will be identified. Using validated and sensitive PCR-assays, the presence of HPV DNA will be analyzed in all available smears from each participant (on an average four smears per individual, giving totally about 4,088 smears).HPV persistence, HPV16/18/45 viral load and HLA (types DQ6 and DR15) will be analyzed for all included women. Relative risks of cervical adenocarcinoma for oncogenic HPV infections, HPV persistence,HPV16/18/45 high viral load, HLA haplotype and interactions between these factors will be estimated with conditional logistic regression. The likelihood ratio test will be used to discriminate between nested models. Statistical power calculations produced for the specific aims show that our study is adequately sized.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA111720-03
Application #
7227781
Study Section
Special Emphasis Panel (ZRG1-HOP-N (02))
Program Officer
Starks, Vaurice
Project Start
2005-05-01
Project End
2010-04-30
Budget Start
2007-07-09
Budget End
2010-04-30
Support Year
3
Fiscal Year
2007
Total Cost
$395,107
Indirect Cost
Name
Karolinska Institute
Department
Type
DUNS #
350582235
City
Stockholm
State
Country
Sweden
Zip Code
171 7-7
Lu, Donghao; Sundström, Karin; Sparén, Pär et al. (2016) Bereavement Is Associated with an Increased Risk of HPV Infection and Cervical Cancer: An Epidemiological Study in Sweden. Cancer Res 76:643-51
Sundström, Karin; Ploner, Alexander; Arnheim-Dahlström, Lisen et al. (2015) Interactions Between High- and Low-Risk HPV Types Reduce the Risk of Squamous Cervical Cancer. J Natl Cancer Inst 107:
Sundström, Karin; Ploner, Alexander; Dahlström, Lisen Arnheim et al. (2013) Prospective study of HPV16 viral load and risk of in situ and invasive squamous cervical cancer. Cancer Epidemiol Biomarkers Prev 22:150-8
Sundstrom, Karin; Eloranta, Sandra; Sparen, Par et al. (2010) Prospective study of human papillomavirus (HPV) types, HPV persistence, and risk of squamous cell carcinoma of the cervix. Cancer Epidemiol Biomarkers Prev 19:2469-78
Dahlström, Lisen Arnheim; Ylitalo, Nathalie; Sundström, Karin et al. (2010) Prospective study of human papillomavirus and risk of cervical adenocarcinoma. Int J Cancer 127:1923-30