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Methylation of High-Risk Human Papillomavirus Genomes are Associated with Cervical Precancer in HIV-positive Women
- Source :
- Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, vol 27, iss 12
- Publication Year :
- 2018
-
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: We designed a case–control study within the Women's Interagency HIV Study (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. 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.
- Subjects :
- 0301 basic medicine
Oncology
Adult
medicine.medical_specialty
Epidemiology
HIV Infections
Cervical Cancer
Cervical intraepithelial neoplasia
Medical and Health Sciences
Methylation
Article
Vaccine Related
03 medical and health sciences
0302 clinical medicine
Clinical Research
Risk Factors
Internal medicine
Genetics
Medicine
Humans
Cervix
Cancer
Cervical cancer
business.industry
Prevention
Human Genome
Papillomavirus Infections
virus diseases
Genomics
medicine.disease
Confidence interval
female genital diseases and pregnancy complications
Infectious Diseases
030104 developmental biology
medicine.anatomical_structure
CpG site
030220 oncology & carcinogenesis
Case-Control Studies
DNA methylation
Cohort
Sexually Transmitted Infections
HIV/AIDS
Female
HPV and/or Cervical Cancer Vaccines
Infection
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, vol 27, iss 12
- Accession number :
- edsair.doi.dedup.....60de4daf04751f53c2887645accef1be