Disparities in Cervical Cancer Precursors and Deregulation of Imprinted Genes

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Abstract Although screening for uterine cervical intraepithelial neoplasia (CIN) and its aggressive treatment has resulted in decreased cervical cancer incidence and mortality, an estimated 11,000 cases of invasive cen/ical cancer (ICC) and 40,000 cases of carcinoma in situ (CIS) continue to be diagnosed every year in the United States. ICC incidence is 60% higher and mortality over two times higher in African Americans (AA) compared to whites. Such disparate rates in incidence and mortality are despite comparable screening rates to detect precursor lesions and comparable prevalence of'high risk' human papillomavirus (HPV) infection and co-factors such as cigarette smoking. Reasons for such disparities are largely unknown but may involve both factors related to differences in medical care, genetics and epigenetics. We have recentiy been funded to evaluate the extent to which epigenetic deregulation of epigenetically labile loci predict progression of CINl to severe intraepithelial neoplasia and cervical cancer (CIN2 or worse) in 1,500 Whites, African and Hispanics (R01 CA142983). On average, ~1/3 of CINl in women aged 25+ years progress to CIN2+. While genetic/epigenetic factors associated with a more aggressive phenotype in AA may explain some ofthe disparities observed, social and medical factors are also likely to be important determinants. For this application, our central hypothesis is that social and medical factors, including suboptimal provider communication and access to care, contribute substantially to inadequate follow-up of cervical cancer precursor lesions, leading to later stage at diagnosis observed in minority populations. We will enroll up to 500 histologically confirmed CINl cases (about one third of CIN cases that we anticipate will not adhere to scheduled appointments) to address the following specific aims: Aim 1: Identify factors associated with poor adherence to scheduled follow-up visits. We will conduct in-depth interviews among the first 20-25 African Americans, Latina and white women who fail to keep scheduled 6-month follow-up appointments, following a CIN1 diagnosis. Aim 2: Based on factors identified in Aim 1, develop and administer a questionnaire to determine the extent to which previously identified factors such as access to care, suboptimal patient/provider communication, and other social factors identified through in-depth interviews are associated with progression to CIN2 or worse and whether this association varies by race/ethnicity; Aim S: Develop a theory-informed intervention to increase adherence to scheduled appointments, anticipating up to 50% of these women adhere to a follow-up visit. Significance. Identifying factors associated with non-adherence to follow-up and if it varies by race, in the CINl population will lead to better focused interventions to increase adherence, and decreases in the risk of progression to ICC disparities. The proposed study will also decrease attrition in the parent study, and preliminary data generated will be essential for a larger study that will be led by Dr. Wordlaw-Stinson.