Abstract LB153: Concordance between self-collected vaginal and physician-collected cervical samples using PCR-based HPV DNA and host cell DNA methylation tests

Abstract Introduction: Cervical cancer incidence is 32% higher among Latinas in the U.S. and 78% higher among women in Puerto Rico compared to non-Latina White women, yet it is preventable through screening. Vaginal self-sampling for PAP and oncogenic Human Papilloma Virus (HPV) testing is an alternative for Latinas with public insurance or uninsured, who are less likely to seek cervical cancer screening. The CervicalMethDx test, a DNA methylation algorithm identifying HPV-positive women at risk for Cervical Intraepithelial Neoplasia (CIN) grades 2/3, assessed concordance between paired brush and urine samples. We hypothesized concordance between self- and physician-collected samples, simultaneously tested with PCR-based high-risk HPV (hrHPV) DNA and the CervicalMethDx test. Methods: To examine concordance between self (Copan MSwabs)- and physician-collected (PreservCyt) samples, an isothermal HPV test (Atila Biosystems) was used for hrHPV detection and CervicalMethDx (LifeGene-Biomarks) test to quantify ZNF516, FKBP6, and INTS1 promoter DNA methylation, estimating risk of premalignant cervical cancer lesions. Cell numbers between MSwabs and PreservCyt samples were compared using Ct values as a proxy. Questionnaires gathered risk factor data, and a 5-item Likert scale assessed comfort, acceptability, difficulty, and sampling preference. Results: 119 women (median age: 44 years [interquartile range (IQR): 35-52]; range 21-63) were enrolled under IRB approval. Most women were Puerto Ricans (86.6%), obtained undergraduate or technical credentials (57.2%), unmarried (67.2%), had Medicaid or lacked insurance (60.5%) and did not have premalignant lesions (91.7%). MSwabs samples [n = 117, median Ct = 22.6 (IQR: 20.9 - 26.6)] showed comparable cell numbers to PreservCyt samples [n = 119, median Ct = 22.8 (IQR: 21.5 - 24.3)] (p = 0.91) for HPV testing, but provided more cells for bisulphite-treated DNA used by CervicalMethDx test: MSwabs [n = 113, median Ct = 25.5 (IQR: 24.8 -27.2)]; PreservCyt [n = 118, median Ct = 28.8 (IQR: 26.4 - 31.0)] (p < 0.0001). Concordance was high for hrHPV (82.4%), HPV16 (97.5%) and HPV18 (99.2%). Concordance Correlation Coefficients for methylation levels between MSwabs and PreservCyt samples revealed weak agreement for ZNF516 (0.030), FKBP6 (0.020), and INTS1 (0.036). Most women favored self-sampling (87.4%), reporting comfort (74.8%), ease (82.4%), and acceptability (78.2%). Conclusion: The concordance of HPV tests in MSwabs samples suggests passenger hrHPV presence in the vagina. The lack of concordance in CervicalMethDx results may stem from the low prevalence of premalignant lesions among participants, leading to variable methylation patterns. Overall, self-sampling was well-accepted and preferred by most women, showcasing its promise as an alternative tool to improve women’s reproductive health. Citation Format: Andrea López-Marrero, Ashley Ramos-López, Fernando T. Zamunér, Bianka Morales-Pomalaza, Álvaro Gutiérrez, Carolina Larronde-Rabanal, Paola Quiñonez-Méndez, Amanda García-Negrón, Guie Beeu Guerrero-Hunt, Aniris Román-Cuevas, Nicole Morant, Teresa Díaz-Montes, Bruce J. Trock, Josefina Romaguera, Mariana Brait, David Sidransky, Rafael Guerrero-Preston. Concordance between self-collected vaginal and physician-collected cervical samples using PCR-based HPV DNA and host cell DNA methylation tests [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB153.