Evidence map›Paper›PMID 23419152›Full record

ArticleGenome medicine2013

Identification and functional validation of HPV-mediated hypermethylation in head and neck squamous cell carcinoma.

Matthias Lechner, Tim Fenton, James West, Gareth Wilson, Andrew Feber, Stephen Henderson, Christina Thirlwell, Harpreet K Dibra, Amrita Jay, Lee Butcher and 9 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 2 pooled it
8.8field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 130 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Characterization of Epigenomic Alterations in HPV16+ Head and Neck Squamous Cell Carcinomas.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022
    Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Identification of HPV16-p16Epigenetics · 2021
    Article
  19. Role of Virus-Induced Host Cell Epigenetic Changes in Cancer.International journal of molecular sciences · 2021
    Review
  20. Review

14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 4 institutions in 2 countries.

Matthias LechnerUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD ; Head and Neck Centre, University College London Hospitals NHS Trust, Euston Road, London, NW1 2PG.
Tim FentonUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD.
James WestUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD.
Gareth WilsonUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD.
Andrew FeberUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD.
Stephen HendersonUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD.
Christina ThirlwellUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD.
Harpreet K DibraUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD.
Amrita JayDepartment of Histopathology, University College London Hospitals NHS Trust, Rockefeller Building, University Street, London, WC1E 6JJ.
Lee ButcherUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD.
Ankur R ChakravarthyUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD.
Fiona GratrixUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD.
Nirali PatelUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD.
Francis VazHead and Neck Centre, University College London Hospitals NHS Trust, Euston Road, London, NW1 2PG.
Paul O'FlynnHead and Neck Centre, University College London Hospitals NHS Trust, Euston Road, London, NW1 2PG.
Nicholas KalavrezosHead and Neck Centre, University College London Hospitals NHS Trust, Euston Road, London, NW1 2PG.
Andrew E TeschendorffUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD.
Chris BoshoffUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD.
Stephan BeckUCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6DD.
University College London · GBCRUK Lung Cancer Centre of Excellence · GBCancer Institute (WIA) · INUniversity College London Hospitals NHS Foundation Trust · GB

Funding

Cancer Research UK 12183Cancer Research UK 13100
6 · The paper itself

Abstract

backgroundHuman papillomavirus-positive (HPV+) head and neck squamous cell carcinoma (HNSCC) represents a distinct clinical and epidemiological condition compared with HPV-negative (HPV-) HNSCC. To test the possible involvement of epigenetic modulation by HPV in HNSCC, we conducted a genome-wide DNA-methylation analysis.

methodsUsing laser-capture microdissection of 42 formalin-fixed paraffin wax-embedded (FFPE) HNSCCs, we generated DNA-methylation profiles of 18 HPV+ and 14 HPV- samples, using Infinium 450 k BeadArray technology. Methylation data were validated in two sets of independent HPV+/HPV- HNSCC samples (fresh-frozen samples and cell lines) using two independent methods (Infinium 450 k and whole-genome methylated DNA immunoprecipitation sequencing (MeDIP-seq)). For the functional analysis, an HPV- HNSCC cell line was transduced with lentiviral constructs containing the two HPV oncogenes (E6 and E7), and effects on methylation were assayed using the Infinium 450 k technology. RESULTS AND DISCUSSION: Unsupervised clustering over the methylation variable positions (MVPs) with greatest variation showed that samples segregated in accordance with HPV status, but also that HPV+ tumors are heterogeneous. MVPs were significantly enriched at transcriptional start sites, leading to the identification of a candidate CpG island methylator phenotype in a sub-group of the HPV+ tumors. Supervised analysis identified a strong preponderance (87%) of MVPs towards hypermethylation in HPV+ HNSCC. Meta-analysis of our HNSCC and publicly available methylation data in cervical and lung cancers confirmed the observed DNA-methylation signature to be HPV-specific and tissue-independent. Grouping of MVPs into functionally more significant differentially methylated regions identified 43 hypermethylated promoter DMRs, including for three cadherins of the Polycomb group target genes. Integration with independent expression data showed strong negative correlation, especially for the cadherin gene-family members. Combinatorial ectopic expression of the two HPV oncogenes (E6 and E7) in an HPV- HNSCC cell line partially phenocopied the hypermethylation signature seen in HPV+ HNSCC tumors, and established E6 as the main viral effector gene.

conclusionsOur data establish that archival FFPE tissue is very suitable for this type of methylome analysis, and suggest that HPV modulates the HNSCC epigenome through hypermethylation of Polycomb repressive complex 2 target genes such as cadherins, which are implicated in tumor progression and metastasis.

Identifiers

PMID23419152
PMCPMC3706778
OpenAlexW2115640312

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Registered trials

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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.