Methylation of High-Risk Human Papillomavirus Genomes Are Associated with Cervical Precancer in HIV-Positive Women
Year: 2018
Type: article
Study design: Observational Study
Abstract: BACKGROUND: HIV-positive women are at substantial risk of HPV-associated cervical neoplasia caused by high-risk (HR) HPVs. Methylation of the HPV genome is associated with cervical intraepithelial neoplasia grade 3 (CIN3) in HIV-negative women, yet it is unknown whether this holds true for HIV-positive women. METHODS: = 23; 32%) had a separate control for each HR-HPV type. We developed and utilized next-generation sequencing (NGS) methylation assays for 12 different HR-HPVs, focusing on CpG sites in the L1/L2 regions. RESULTS: Significant case-control differences in individual CpG site methylation levels were observed for multiple alpha-9 (HPV16/31/35/58) and alpha-7 HPV (HPV18/39/45) types, based on dichotomization of tertile levels (T3 vs. T1 and T2). Analyses combining homologous CpG sites [e.g., HPV16-L1-5608/HPV31-L1-5521/HPV35-L2L1-5570; OR = 7.28; 95% confidence interval (CI): 2.75-19.3], and (e.g., HPV18-L1-7062/HPV45-L1-7066; OR = 6.94; 95% CI: 1.23-39.3) were significant in separate case-control comparisons. In cases with multiple HR-HPVs, we tested and confirmed the hypothesis that one HR-HPV type would have higher methylation than other types detected, consistent with there being a single HR-HPV causally related to a lesion. CONCLUSIONS: CIN3 is associated with elevated L1/L2 CpG methylation levels in HIV-positive women. IMPACT: HPV DNA CpG methylation is a promising triage option in HIV-positive women testing positive for HR-HPV types and provides risk attribution in women with multiple HPV type infections.
Authors: Ana Gradissimo, Jessica Lam, John D. Attonito, Joel Palefsky, L. Stewart Massad, Xianhong Xie, Isam-Eldin Eltoum, Lisa Rahangdale, Margaret A. Fischl, Kathryn Anastos, Howard Minkoff, Xiaonan Xue, Gypsyamber D'Souza, Lisa C. Flowers, Christine Colie, Sadeep Shrestha, Nancy A. Hessol, Howard D. Strickler, Robert D. Burk
Institutions: Albert Einstein College of Medicine, University of California, San Francisco, Washington University in St. Louis, University of Alabama, University of Alabama at Birmingham, University of North Carolina at Chapel Hill, University of Miami, Montefiore Medical Center, Montefiore Health System, Maimonides Medical Center, Johns Hopkins University, Emory University, Georgetown University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Georgia Clinical and Translational Science Alliance, National Institutes of Health, University of California, San Francisco, National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, National Institute of Dental and Craniofacial Research, Office of Research on Women's Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1089263533, G1111999087, G1114015694, G1166984944, G12089860, G1446261281, G1835874845, G2117662475, G2127051194, G2227505777, G2277270920, G2583540734, G259661504, G2638674773, HPV & Cervix Neoplasia in a Large, Long Term HIV + Cohort, G3001095189, G3089064904, Next Generation of HPV and Cervical Cancer Research in HIV+ Women, G3481933404, Miami Womens Interagency HIV Study WIHS, G3671922257, G3942807564, G4019075231, G4263984760, G4333671923, G4361283536, G4371267688, G4500389830, G4558954805, Effects of HLA and KIR genotype on HIV and HCV, G4763761376, Molecular Methods to Improve Cervical Cancer Screening in HIV+ Women, Chicago WIHS Consortium V (CWC), G5411330681, G5411403494, G5641536491, G5655542889, G5900455136, G592158972, G6068496172, G6300780520, G6341392406, G6384504179, G6533371250, G6576622550, G669420692, G6924000613, G6990385686, University of North Carolina Womens Interagency HIV Study UNC WIHS, G7479905529, G767062161, G773494495, G775892330, G7807729167, G8448522485, G8653535977, G8846374971, UAB-MISS WIHS Cohort, G9000029981, G9000030772, G9000039899, G9000052758, G9000059706, G9000080293, G9000081039, G9000084207, G9000110076, G9000122276, G9000177630, G9000216739, Cancer Center Support Grant, G97119092, G986692823
OpenAlex ID: W2891948837