Evidence map›Paper›PMID 27529629›Full record

ArticlePloS one2016

CpG Methylation Analysis of HPV16 in Laser Capture Microdissected Archival Tissue and Whole Tissue Sections from High Grade Anal Squamous Intraepithelial Lesions: A Potential Disease Biomarker.

Monica Molano, Sepehr N Tabrizi, Suzanne M Garland, Jennifer M Roberts, Dorothy A Machalek, Samuel Phillips, David Chandler, Richard J Hillman, Andrew E Grulich, Fengyi Jin and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Host Cell Deoxyribonucleic Acid Methylation Markers for the Detection of High-grade Anal Intraepithelial Neoplasia and Anal Cancer.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019
    Article
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

14 authors.

Monica MolanoRegional HPV Labnet Reference Laboratory, Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, Victoria, Australia.
Sepehr N TabriziRegional HPV Labnet Reference Laboratory, Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, Victoria, Australia.
Suzanne M GarlandRegional HPV Labnet Reference Laboratory, Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, Victoria, Australia.
Jennifer M RobertsGynaePath, Douglass Hanly Moir Pathology, Macquarie Park, Sydney, Australia.
Dorothy A MachalekRegional HPV Labnet Reference Laboratory, Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, Victoria, Australia.
Samuel PhillipsRegional HPV Labnet Reference Laboratory, Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, Victoria, Australia.
David ChandlerAustralian Genome Research Facility, Perth, Australia.
Richard J HillmanWestern Sydney Sexual Health Centre, Western Sydney Local Health District, Parramatta, New South Wales, Australia.
Andrew E GrulichThe Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Fengyi JinThe Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
I Mary PoyntenThe Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
David J TempletonThe Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Alyssa M CornallRegional HPV Labnet Reference Laboratory, Department of Microbiology and Infectious Diseases, The Royal Women's Hospital, Parkville, Victoria, Australia.
SPANC Study Team

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Incidence and mortality rates of anal cancer are increasing globally. More than 90% of anal squamous cell carcinomas (ASCC) are associated with human papillomavirus (HPV). Studies on HPV-related anogenital lesions have shown that patterns of methylation of viral and cellular DNA targets could potentially be developed as disease biomarkers. Lesion-specific DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissues from existing or prospective patient cohorts may constitute a valuable resource for methylation analysis. However, low concentrations of DNA make these samples technically challenging to analyse using existing methods. We therefore set out to develop a sensitive and reproducible nested PCR-pyrosequencing based method to accurately quantify methylation at 10 CpG sites within the E2BS1, E2BS2,3,4 and Sp1 binding sites in the viral upstream regulatory region of HPV16 genome. Methylation analyses using primary and nested PCR-pyrosequencing on 52 FFPE tissue [26 paired whole tissue sections (WTS) and laser capture microdissected (LCM) tissues] from patients with anal squamous intraepithelial lesions was performed. Using nested PCR, methylation results were obtained for the E2BS1, E2BS2,3,4 and Sp1 binding sites in 86.4% of the WTS and 81.8% of the LCM samples. Methylation patterns were strongly correlated within median values of matched pairs of WTS and LCM sections, but overall methylation was higher in LCM samples at different CpG sites. High grade lesions showed low methylation levels in the E2BS1 and E2BS2 regions, with increased methylation detected in the E2BS,3,4/Sp1 regions, showing the highest methylation at CpG site 37. The method developed is highly sensitive in samples with low amounts of DNA and demonstrated to be suitable for archival samples. Our data shows a possible role of specific methylation in the HPV16 URR for detection of HSIL.

Indexed as

DNA MethylationLaser Capture MicrodissectionAnus NeoplasmsBiopsyCell Line, TumorCpG IslandsDNA, ViralFemaleHuman papillomavirus 16HumansNeoplasm GradingPolymerase Chain ReactionSequence Analysis, DNASquamous Intraepithelial Lesions of the CervixDNA, Viral

Identifiers

PMID27529629
PMCPMC4987059

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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.