ArticleInternational journal of cancer2015
HPV16 methyl-haplotypes determined by a novel next-generation sequencing method are associated with cervical precancer.
Article in International journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Comparison of different mRNA testing technologies with HPV DNA testing for predicting ASCUS triage and post-cone excision outcomes: a systematic review and meta-analysis.Systematic reviews · 2026Pooled it
- The use of human papillomavirus DNA methylation in cervical intraepithelial neoplasia: A systematic review and meta-analysis.EBioMedicine · 2019Pooled it
- Performance of DNA methylation assays for detection of high-grade cervical intraepithelial neoplasia (CIN2+): a systematic review and meta-analysis.British journal of cancer · 2019Pooled it
- High-Throughput Targeted Sequencing Identifies an HPV Methylation Panel for Detecting Cervical Lesion Progression.Journal of medical virology · 2025Article
- Enhancing the sensitivity of non-invasive cervical cancer detection using CpG methylation haplotype profiling.Scientific reports · 2025Article
- Rearrangements of viral and human genomes at human papillomavirus integration events and their allele-specific impacts on cancer genome regulation.Genome research · 2025Article
- A novel human papillomavirus and host DNA methylation score and detection of cervical adenocarcinoma.Journal of the National Cancer Institute · 2023Article
- Methylation haplotypes of the insulin gene promoter in children and adolescents with type 1 diabetes: Can a dimensionality reduction approach predict the disease?Experimental and therapeutic medicine · 2023Article
- The Improving Risk Informed HPV Screening (IRIS) Study: Design and Baseline Characteristics.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022Article
- Phylogenomic Analysis of Human Papillomavirus Type 31 and Cervical Carcinogenesis: A Study of 2093 Viral Genomes.Viruses · 2021Article
- Genetic and Epigenetic Variations of HPV52 in Cervical Precancer.International journal of molecular sciences · 2021Article
- Primary HPV and Molecular Cervical Cancer Screening in US Women Living With Human Immunodeficiency Virus.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
- Article
- Methylation of CpG 5962 in L1 of the human papillomavirus 16 genome as a potential predictive marker for viral persistence: A prospective large cohort study using cervical swab samples.Cancer medicine · 2020Article
- Methylation of High-Risk Human Papillomavirus Genomes Are Associated with Cervical Precancer in HIV-Positive Women.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 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
- Methylation of the L1 gene and integration of human papillomavirus 16 and 18 in cervical carcinoma and premalignant lesions.Oncology letters · 2018Article
- Utility of high-throughput DNA sequencing in the study of the human papillomaviruses.Virus genes · 2018Review
- Assessment of viral methylation levels for high risk HPV types by newly designed consensus primers PCR and pyrosequencing.PloS one · 2018Article
- Molecular tests potentially improving HPV screening and genotyping for cervical cancer prevention.Expert review of molecular diagnostics · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
We have developed and evaluated a next-generation bisulfite sequencing (NGS) assay to distinguish HPV16 cervical precancer (CIN2-3; N=59) from HPV16-positive transient infections (N=40). Cervical DNA was isolated and treated with bisulfite and HPV16 methylation was quantified by (i) amplification with barcoded primers and massively parallel single molecule sequencing and (ii) site-specific pyrosequencing. Assays were evaluated for agreement using intraclass correlation coefficients (ICC). Odds ratios (OR) for high methylation vs. low methylation were calculated. Single site pyrosequencing and NGS data were correlated (ICC=0.61) and both indicated hypermethylation was associated with precancer (ORs of 2-37). Concordant NGS and pyrosequencing results yieled ORs that were stronger when compared with using either assay separately. Within the L1 region, the ORs for CIN2-3 were 14.3 and 22.4 using pyrosequencing and NGS assays, respectively; when both methods agreed the OR was 153. NGS assays provide methylation haplotypes, termed methyl-haplotypes from single molecule reads: cases had increased methyl-haplotypes with ≥1 methylated CpG site(s) per fragment compared with controls, particularly in L1 (p=3.0×10(-8)). The maximum discrimination of cases from controls for a L1 methyl-haplotype had an AUC of 0.89 corresponding to a sensitivity of 92.5% and a specificity of 73.1%. The strengthening of the OR when the two assays were concordant suggests the true association of CpG methylation with precancer is stronger than with either assay. As cervical cancer prevention moves to DNA testing methods, DNA based biomarkers, such as HPV methylation could serve as a reflex strategy to identify women at high risk for cervix cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.