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Grant Details

Grant Number: 3R01CA123467-05S1 Interpret this number
Primary Investigator: Gravitt, Patti
Organization: Johns Hopkins University
Project Title: HPV Infection Among Perimenopausal Women in the 1945-64 Birth Cohor
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): Understanding the natural history of human papillomavirus (HPV) infection throughout the female life span will be critical in guiding future cervical cancer prevention programs, including screening and HPV vaccination. Age-specific trends of HPV prevalence show a second peak of HPV among older women in some populations. Few studies have been conducted to understand this observation, and historical cohorts will be of little value for further investigation. Women currently reaching the age of menopause in the US have experienced different risks throughout their lifetime due to the strong cohort effects that resulted from the sexual revolution that occurred in the 1960s and 1970s. It is therefore imperative to study contemporaneous cohorts of women through the menopausal transition to gain an understanding of the natural history of HPV infection in later life, including the risk of new HPV infections, reactivation of previously acquired infections, and persistence and disease progression of either reactivated or newly acquired infection. We propose to conduct a prospective cohort study of 1500 women belonging to the 1945-1965 'baby boomer' birth cohort to accomplish the following specific aims: (1) To compare the prevalence, (2) incidence, and (3) duration of HPV infection and squamous intraepithelial lesions (SIL) in pre-, peri-, and post-menopausal women, and (4) to estimate the minimum fraction of incident HPV DMA detection and seroconversion associated with reactivation vs. new sexual exposures. We will enroll a racially and socioeconomically diverse cohort in Baltimore, Maryland and follow the women for HPV and SIL every four months over a two year period. Our observational data will be supported by detailed molecular epidemiologic characterization of the viral infection (viral load, variant status, and gene expression) and the host response (cervical cytokine expression) among women with persistent vs. resolving infections. The successful completion of the study will provide stable estimates of risk of new HPV detection and SIL as a function of menopausal transitions and sexual exposures vs. reactivation in a contemporaneous cohort of aging women with the US. This information will be critical for development of cost-effective cervical cancer prevention policies. The complementary molecular studies will add important biological information that may lead to new approaches in screening and treatment of cervical HPV infections and neoplasia.

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Publications

Increased age and race-specific incidence of cervical cancer after correction for hysterectomy prevalence in the United States from 2000 to 2009.
Authors: Rositch AF, Nowak RG, Gravitt PE
Source: Cancer, 2014 Jul 1;120(13), p. 2032-8.
EPub date: 2014 May 12.
PMID: 24821088
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Characterizing the temporal dynamics of human papillomavirus DNA detectability using short-interval sampling.
Authors: Liu SH, Cummings DA, Zenilman JM, Gravitt PE, Brotman RM
Source: Cancer Epidemiol Biomarkers Prev, 2014 Jan;23(1), p. 200-8.
EPub date: 2013 Oct 15.
PMID: 24130223
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Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy.
Authors: Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K, Silver MI, Viscidi RP, Burke AE, Ravel J, Gravitt PE
Source: Menopause, 2014 May;21(5), p. 450-8.
PMID: 24080849
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Obesity and human papillomavirus infection in perimenopausal women.
Authors: Liu SH, Rositch AF, Viscidi RP, Silver MI, Burke AE, Gravitt PE
Source: J Infect Dis, 2013 Oct 1;208(7), p. 1071-80.
EPub date: 2013 Jul 9.
PMID: 23840046
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A cohort effect of the sexual revolution may be masking an increase in human papillomavirus detection at menopause in the United States.
Authors: Gravitt PE, Rositch AF, Silver MI, Marks MA, Chang K, Burke AE, Viscidi RP
Source: J Infect Dis, 2013 Jan 15;207(2), p. 272-80.
EPub date: 2012 Dec 12.
PMID: 23242540
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Contributions of recent and past sexual partnerships on incident human papillomavirus detection: acquisition and reactivation in older women.
Authors: Rositch AF, Burke AE, Viscidi RP, Silver MI, Chang K, Gravitt PE
Source: Cancer Res, 2012 Dec 1;72(23), p. 6183-90.
EPub date: 2012 Sep 27.
PMID: 23019223
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The correlation between human papillomavirus positivity and abnormal cervical cytology result differs by age among perimenopausal women.
Authors: Rositch AF, Silver MI, Burke A, Viscidi R, Chang K, Duke CM, Shen W, Gravitt PE
Source: J Low Genit Tract Dis, 2013 Jan;17(1), p. 38-47.
PMID: 22885643
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Comparison of normalization methods for measuring immune markers in cervical secretion specimens.
Authors: Marks MA, Eby Y, Howard R, Gravitt PE
Source: J Immunol Methods, 2012 Aug 31;382(1-2), p. 211-5.
EPub date: 2012 Jun 4.
PMID: 22677266
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The known unknowns of HPV natural history.
Authors: Gravitt PE
Source: J Clin Invest, 2011 Dec;121(12), p. 4593-9.
EPub date: 2011 Dec 1.
PMID: 22133884
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Differences in the concentration and correlation of cervical immune markers among HPV positive and negative perimenopausal women.
Authors: Marks MA, Viscidi RP, Chang K, Silver M, Burke A, Howard R, Gravitt PE
Source: Cytokine, 2011 Dec;56(3), p. 798-803.
EPub date: 2011 Oct 19.
PMID: 22015106
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Adult male circumcision: will it reduce disease caused by human papillomavirus?
Authors: Viscidi RP, Shah KV
Source: J Infect Dis, 2010 May 15;201(10), p. 1447-9.
PMID: 20370482
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Progress and pitfalls in defining the influence of highly active antiretroviral therapy on human papillomavirus-associated cervical disease.
Authors: Gravitt PE, Kirk GD
Source: J Infect Dis, 2010 Mar;201(5), p. 650-2.
PMID: 20105079
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