Title |
Methylation of High-Risk Human Papillomavirus Genomes are Associated with Cervical Precancer in HIV-positive Women
|
---|---|
Published in |
Cancer Epidemiology, Biomarkers & Prevention, December 2018
|
DOI | 10.1158/1055-9965.epi-17-1051 |
Pubmed ID | |
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 |
Abstract |
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. We designed a case-control study within the WIHS cohort comparing HIV-positive CIN3 cases (N=72) to HIV-positive controls without detectable CIN2+. The unit of analysis and matching was HPV type infection. Cases with ≥2 HR-HPV types (N=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. 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 versus T1 and T2). Analyses combining homologous CpG sites (e.g., HPV16-L1-5608/HPV31-L1-5521/HPV35-L2L1-5570; odds ratio [OR]=7.28; 95% 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. CIN3 is associated with elevated L1/L2 CpG methylation levels in HIV-positive women. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 4 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 4 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 28 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 5 | 18% |
Student > Bachelor | 4 | 14% |
Researcher | 4 | 14% |
Student > Doctoral Student | 2 | 7% |
Student > Ph. D. Student | 2 | 7% |
Other | 3 | 11% |
Unknown | 8 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 7 | 25% |
Biochemistry, Genetics and Molecular Biology | 6 | 21% |
Nursing and Health Professions | 2 | 7% |
Immunology and Microbiology | 1 | 4% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
Other | 2 | 7% |
Unknown | 9 | 32% |