This proposal builds upon and expands studies funded under our current EXPORT Center, which investigate the molecular and biologic basis of persistent high risk human papillomavirus (HR-HPV) infection in female college students. While HR-HPV infection is the major cause of cervical cancer, most HPV infections clear in a matter of months, and only women who have persistent HR-HPV infection are truly at risk for cancer. If 'biomarkers' of HPV persistence can be identified at a first visit, then careful follow-up care could be directed to those women that really need it, in a cost effective and efficient fashion. Furthermore, there is considerable disparity in cervical cancer incidence and mortality rates between European American (EA) and African American (AA) women nationwide. Specifically, in South Carolina, AA women are 1.6-fold more likely to be diagnosed with cervical cancer, and 2.5 times more likely to die of it than EA women. While much of this disparity has been attributed to differences in access to care, we now have evidence that biological and molecular mechanisms may also play a role. During the current EXPORT funding period we initiated the Carolina Women's Care Study (CWCS) in which the HPV status and type in Pap test material from freshman female college students attending either the University of South Carolina (USC) or Claflin University (CU) was determined every six months for the duration of their college experience. We also followed cervical cytology (from Pap tests), determined the cytokine profiles in cervical mucus, and administered questionnaires at each visit that collected information concerning lifestyle factors, stress, smoking, discrimination, diet, and physical activity. In addition, blood was collected during the first visit for DNA isolation and characterization of single nucleotide polymorphisms (SNPs) in the promoter region of cytokine genes (IL-6, TNF-alpha, RANTES, and GM-CSF) that may be involved in HPV persistence. A second Pap test was also collected for RNA isolation. Initial results from the CWCS indicate that AA women have a different HR-HPV type distribution than EA women; that AA women clear certain HR-HPV types slower than EA women; and that AA women are more likely to develop high grade lesions than EA women. Any potential useful biomarker of progression would need to be detectable in exfoliated cells, in order to be clinically useful in the triage of women at risk for cervical cancer. Therefore, during our previous EXPORT funding period we perfected techniques for extracting and purifying high quality RNA, suitable for microarrays, from Pap test material, and our preliminary studies of gene expression in these samples demonstrated the feasibility of conducting gene expression profiling studies using RNA from cervical exfoliated cells.

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Exploratory Grants (P20)
Project #
5P20MD001770-08
Application #
8579991
Study Section
Special Emphasis Panel (ZMD1-PA (01))
Project Start
2005-09-30
Project End
2015-02-28
Budget Start
2012-03-19
Budget End
2013-02-28
Support Year
8
Fiscal Year
2012
Total Cost
$186,418
Indirect Cost
$48,562
Name
University of South Carolina at Columbia
Department
Type
DUNS #
041387846
City
Columbia
State
SC
Country
United States
Zip Code
29208
Anderson, Erin L; Banister, Carolyn E; Kassler, Susannah et al. (2016) Human Papillomavirus Type 16 L2 DNA Methylation in Exfoliated Cervical Cells From College-Age Women. J Low Genit Tract Dis 20:332-7
Spiryda, Lisa Beth; Whitaker, Kara M; Messersmith, Amy et al. (2016) Clinical Utility of Molecular Biomarkers in Cervical Squamous Intraepithelial Lesions in a Young Adult Population. J Low Genit Tract Dis 20:26-30
Tomar, Swati; Graves, Christian A; Altomare, Diego et al. (2016) Human papillomavirus status and gene expression profiles of oropharyngeal and oral cancers from European American and African American patients. Head Neck 38 Suppl 1:E694-704
Banister, Carolyn E; Messersmith, Amy R; Cai, Bo et al. (2015) Disparity in the persistence of high-risk human papillomavirus genotypes between African American and European American women of college age. J Infect Dis 211:100-8
Wilson, Sacoby; Burwell-Naney, Kristen; Jiang, Chengsheng et al. (2015) Assessment of sociodemographic and geographic disparities in cancer risk from air toxics in South Carolina. Environ Res 140:562-8
Graves, Christian A; Jones, Ashley; Reynolds, Justin et al. (2015) Neuroendocrine Merkel cell carcinoma is associated with mutations in key DNA repair, epigenetic and apoptosis pathways: a case-based study using targeted massively parallel sequencing. Neuroendocrinology 101:112-9
Xu, Hanwen; Pirisi, Lucia; Creek, Kim E (2015) Six1 overexpression at early stages of HPV16-mediated transformation of human keratinocytes promotes differentiation resistance and EMT. Virology 474:144-53
Bellinger, Jessica D; Millegan, Whitney; Abdalla, Azza E (2015) "I'm not ashamed to talk on it!": African-American women's decisions about cervical cancer prevention and control in South Carolina. Womens Health Issues 25:120-7
Jaggers, J R; Hand, G A; Dudgeon, W D et al. (2015) Aerobic and resistance training improves mood state among adults living with HIV. Int J Sports Med 36:175-81
Rice, LaShanta J; Brandt, Heather M; Hardin, James W et al. (2015) Exploring perceptions of cancer risk, neighborhood environmental risks, and health behaviors of blacks. J Community Health 40:419-30

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