HPV Type Distribution and Biomarkers of Cervical Neoplasia Progression in Africa

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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.