Abstract 1978: Community Genomic Health Promotion Program evaluates precision DNA methylation biomarkers for use in self-testing and collection kits in urine, to increase cervical cancer screening rates among Latina women
Authors: Ili Carmen , Brebi Priscilla , López Jaime , Zamunér Fernando T. , Purcell-Wiltz Ana , García-Negrón Amanda , Vale-Lassalle Keilyn , Gosala Keerthana , Otero-García Mirla , Rivero-Maldonado Camila , Torres-Rivera Teresa , Pérez-Vicente Adriana , Ramos-López Ashley , Sidransky David , Brait Mariana , Guerrero-Preston Rafael E. 
Published: April 2023

Cervical cancer incidence is 32% higher among Latina women in the United States (US) and 78% higher among women in Puerto Rico compared to non-Latina White (NLW) women, yet it is largely preventable through screening. Latina women with public insurance or uninsured are significantly less likely to have had a Pap test, undergo fewer Pap and high-Risk Human Papilloma Virus (HPV) testing than NLW and Black women, and are less likely than women of other races/ethnicities to return for recommended follow-up after an abnormal Pap test. Utilizing the PRECEDE-PROCEED model, Community Based Participatory Research strategies and the NIH I-Corps hypothesis-driven research method of customer discovery, we implemented the Community Genomic Health Promotion Program in Federally Qualified Health Centers to evaluate cervical cancer screening needs in six rural municipalities in Puerto Rico. We recently validated in clinical liquid cytology samples that the CervicalMethDx test, a precision DNA methylation test, can identify HPV positive women most likely to be diagnosed with Cervical Intraepithelial Neoplasia (CIN) grades 2 and 3. We hypothesized that a molecular pathology test which identifies advanced premalignant cervical lesions in urine, can be distributed by commercial channels targeting populations with low screening rates. The CervicalMethDx quantitative Methylation Specific PCR (qMSP) test was used to quantify ZNF516, FKBP6 and INTS1 promoter DNA methylation in well-characterized, discarded, liquid cytology clinical samples from Puerto Rico. We then tested the CervicalMethDx test concordance on paired cytobrush (n=82) and urine samples (n=82) from Chile. The CervicalMethDx test correctly classified 86% of discarded liquid cytology clinical samples from HPV-positive women, when comparing DNA methylation in CIN2/CIN3 samples (n=47) to samples with a cervical pathology diagnosis of No Intraepithelial Lesions or Malignancy (n=18), with 83% Sensitivity, 94% Specificity, Area Under the Curve (AUC) of 0.88, and 98% positive predictive value (PPV). The concordance of the CervicalMethDx test in paired brush and urine samples was moderate (rho=0.45). The Wilcoxon signed-rank test showed no statistically significant differences for the CervicalMethDx test in paired brush and urine samples (p=0.14) These encouraging preliminary results show the successful identification of advanced premalignant cervical lesions in liquid cytology media and urine samples from Latina women. The data suggests that urine should be explored as a biofluid for cervical cancer screening. Future research may lead to expanded screening options, enabling women with low access to health care (public insurance or uninsured) to collect a specimen at home, and either send it to a testing facility or perform the test at home.

Citation Format: Carmen Ili, Priscilla Brebi, Jaime López, Fernando T. Zamunér, Ana Purcell-Wiltz, Amanda García-Negrón, Keilyn Vale-Lassalle, Keerthana Gosala, Mirla Otero-García, Camila Rivero-Maldonado, Teresa Torres-Rivera, Adriana Pérez-Vicente, Ashley Ramos-López, David Sidransky, Mariana Brait, Rafael E. Guerrero-Preston. Community Genomic Health Promotion Program evaluates precision DNA methylation biomarkers for use in self-testing and collection kits in urine, to increase cervical cancer screening rates among Latina women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1978.