ArticleGynecologic oncology2015
HPV16 CpG methyl-haplotypes are associated with cervix precancer and cancer in the Guanacaste natural history study.
Article in Gynecologic oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The use of human papillomavirus DNA methylation in cervical intraepithelial neoplasia: A systematic review and meta-analysis.EBioMedicine · 2019Pooled it
- High-Throughput Targeted Sequencing Identifies an HPV Methylation Panel for Detecting Cervical Lesion Progression.Journal of medical virology · 2025Article
- A novel human papillomavirus and host DNA methylation score and detection of cervical adenocarcinoma.Journal of the National Cancer Institute · 2023Article
- Effects of CpG sites methylation modification of HPV16 integration essential gene on the proliferation of cervical cancer cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Genetic and Epigenetic Variations of HPV52 in Cervical Precancer.International journal of molecular sciences · 2021Article
- The precision prevention and therapy of HPV-related cervical cancer: new concepts and clinical implications.Cancer medicine · 2018Review
- Outcomes of Conservative Management of High Grade Squamous Intraepithelial Lesions in Young Women.Journal of lower genital tract disease · 2018Article
- Human Papillomavirus DNA Methylation as a Biomarker for Cervical Precancer: Consistency across 12 Genotypes and Potential Impact on Management of HPV-Positive Women.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Utility of high-throughput DNA sequencing in the study of the human papillomaviruses.Virus genes · 2018Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
objectiveTo evaluate HPV16 CpG methylation and methyl-haplotypes and their association with cervix precancer and cancer utilizing massively parallel single molecule next-generation sequencing (NGS).
methodsA nested case-control study of HPV16 positive women was performed in a prospective cohort from Guanacaste, Costa Rica designed to study the natural history of HPV and cervical neoplasia. Controls encompassed 31 women with transient infections; there were 44 cases, including 31 women with CIN3 and 13 with cervical cancer. DNA samples from exfoliated cervical cells were treated with bisulfite and four regions (E6, E2, L2 and L1) were amplified with barcoded primers and tested by NGS. CpG methylation was quantified using a bioinformatics pipeline.
resultsMedian methylation levels were significantly different between the CIN3+ cases versus controls in the E2, L2, and L1 regions. Methyl-haplotypes, specifically in 5 CpG sites included in the targeted L2 region, with the pattern "--+-+" had the highest Area Under the Curve value (AUC=88.40%) observed for CIN3 vs. CONTROLS: The most significant CpG site, L2 4277, determined by bisulfite NGS had an AUC=78.62%.
conclusionsThis study demonstrates that NGS of bisulfite treated HPV DNA is a useful and efficient technique to survey methylation patterns in HPV16. This procedure provides quantitative information on both individual CpG sites and methyl-haplotypes that identify women with elevated present or subsequent risk for HPV16 CIN3 and cancer.
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