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.
Pharmacology, Toxicology and Pharmaceutical Science
1
3%
Other
2
6%
Unknown
11
31%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 September 2018.
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