Evidence map›Paper›PMID 30060049›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2019

Host Cell Deoxyribonucleic Acid Methylation Markers for the Detection of High-grade Anal Intraepithelial Neoplasia and Anal Cancer.

Ramon P van der Zee, Olivier Richel, Carel J M van Noesel, Putri W Novianti, Iuliana Ciocanea-Teodorescu, Annina P van Splunter, Sylvia Duin, Guido E L van den Berk, Chris J L M Meijer, Wim G V Quint and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

26 citing papers in PubMed, 43 citations in OpenAlex.

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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

13 authors at 4 institutions in 1 country.

Ramon P van der ZeeDepartment of Pathology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Olivier RichelDivision of Infectious Diseases, Department of Internal Medicine, Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Carel J M van NoeselDepartment of Pathology, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Putri W NoviantiDepartment of Epidemiology and Biostatistics, Amsterdam University Medical Centers, VU University Medical Center, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Iuliana Ciocanea-TeodorescuDepartment of Epidemiology and Biostatistics, Amsterdam University Medical Centers, VU University Medical Center, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Annina P van SplunterDepartment of Pathology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Sylvia DuinDepartment of Pathology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Guido E L van den BerkDepartment of Internal Medicine, Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, The Netherlands.
Chris J L M MeijerDepartment of Pathology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Wim G V QuintDelft Diagnostic Laboratory (DDL), Rijswijk, The Netherlands.
Henry J C de VriesDepartment of Dermatology, Amsterdam University Medical Centers, Amsterdam Infection & Immunity Institute, University of Amsterdam, Amsterdam, The Netherlands.
Jan M PrinsDivision of Infectious Diseases, Department of Internal Medicine, Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Renske D M SteenbergenDepartment of Pathology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Amsterdam University Medical Centers · NLDDL Diagnostic Laboratory · NLGGD Amsterdam · NLOLVG · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHigh-grade anal intraepithelial neoplasia (AIN2/3; HGAIN) is highly prevalent in human immunodeficiency virus positive (HIV+) men who have sex with men (MSM), but only a minority will eventually progress to cancer. Currently, the cancer risk cannot be established, and therefore all HGAIN is treated, resulting in overtreatment. We assessed host cell deoxyribonucleic acid (DNA) methylation markers for detecting HGAIN and anal cancer.

methodsTissue samples of HIV+ men with anal cancer (n = 26), AIN3 (n = 24), AIN2 (n = 42), AIN1 (n = 22) and HIV+ male controls (n = 34) were analyzed for methylation of 9 genes using quantitative methylation-specific polymerase chain reaction. Univariable and least absolute shrinkage and selection operator logistic regression, followed by leave-one-out cross-validation, were used to determine the performance for AIN3 and cancer detection.

resultsMethylation of all genes increased significantly with increasing severity of disease (P < 2 × 10-6). HGAIN samples revealed heterogeneous methylation patterns, with a subset resembling cancer. Four genes (ASCL1, SST, ZIC1,ZNF582) showed remarkable performance for AIN3 and anal cancer detection (area under the curve [AUC] > 0.85). ZNF582 (AUC = 0.89), detected all cancers and 54% of AIN3 at 93% specificity. Slightly better performance (AUC = 0.90) was obtained using a 5-marker panel.

conclusionsDNA methylation is associated with anal carcinogenesis. A marker panel that includes ZNF582 identifies anal cancer and HGAIN with a cancer-like methylation pattern, warrantingvalidation studies to verify its potential for screening and management of HIV+ MSM at risk for anal cancer.

Indexed as

DNA MethylationAnus NeoplasmsBiomarkers, TumorCarcinoma in SituCross-Sectional StudiesDNAHIV InfectionsHomosexuality, MaleHumansMaleMiddle AgedMolecular Diagnostic TechniquesPolymerase Chain ReactionBiomarkers, TumorDNAanal canceranal intraepithelial neoplasiaDNA methylation markershuman immunodeficiency virushuman papillomavirus

Identifiers

PMID30060049
PMCPMC6424081
OpenAlexW2884067628

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.