Evidence map›Paper›PMID 33580586›Full record

ArticleMolecular oncology2021

DNA methylation markers have universal prognostic value for anal cancer risk in HIV-negative and HIV-positive individuals.

Ramon P van der Zee, Carel J M van Noesel, Ivonne Martin, Timo J Ter Braak, Daniëlle A M Heideman, Henry J C de Vries, Jan M Prins, Renske D M Steenbergen

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07123558 (Anal Cancer Prevention in High-Risk Categories of Men Who Have Sex With Men - A Danish Prospective Study), which is not on this map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.2field-weighted citation impact, top 8% 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.

NCT07123558 nanot yet recruitingnot on this mapstarted 2025, after this paper: background citation

Anal Cancer Prevention in High-Risk Categories of Men Who Have Sex With Men - A Danish Prospective Study

TypeinterventionalSponsorBispebjerg HospitalRan2025 to 2027Enrolled700ConditionsAnal HSIL, Anal AIN3, Anal HPV InfectionArmsHigh resolution anoscopy
3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 28 citations in OpenAlex.

  1. International journal of molecular sciences · 2025
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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

8 authors at 2 institutions in 2 countries.

Ramon P van der ZeeDepartment of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0003-1325-1901
Carel J M van NoeselDepartment of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Ivonne MartinDepartment of Epidemiology and Data Science, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Timo J Ter BraakDepartment of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Daniëlle A M HeidemanDepartment of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Henry J C de VriesDepartment of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Jan M PrinsDepartment of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Renske D M SteenbergenDepartment of Pathology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0002-2327-9839
Amsterdam University Medical Centers · NLAmsterdam Neuroscience · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Anal cancer has increasing incidence and is preceded by high-grade anal intraepithelial neoplasia (HGAIN; AIN2-3). Previously, we identified and validated several methylation markers for accurate detection of anal cancer and HGAIN with cancer risk in HIV-positive (HIV+) men who have sex with men (MSM). This study aimed to evaluate these markers in HIV-negative risk groups. A cross-sectional series of 176 tissue samples of anal cancer, AIN3, AIN2, AIN1 and control biopsies obtained in HIV-negative women and men was tested for six methylation markers (ASCL1, LHX8, SST, WDR17, ZIC1 and ZNF582). Accuracy for detection of AIN3 and cancer (AIN3+) was determined by univariable and multivariable mixed-effect ordinal logistic regression. Methylation levels of all markers increased with increasing severity of disease (P < 0.0001) and were comparable to results in HIV+ MSM. All markers showed high accuracy for AIN3+ detection [area under the curve (AUC): 0.83-0.86]. The optimal marker panel (ASCL1 and ZIC1; AUC = 0.85 for AIN3+) detected 98% of cancers at 79% specificity. In conclusion, DNA methylation markers show a high diagnostic performance for AIN3+ detection in HIV+ and HIV-negative risk groups, justifying broad application of methylation analysis for anal cancer prevention programmes.

Indexed as

Anus NeoplasmsCarcinoma in SituHIV InfectionsPapillomavirus InfectionsSexual and Gender MinoritiesCross-Sectional StudiesDNA MethylationFemaleHomosexuality, MaleHumansMalePrognosisanal canceranal intraepithelial neoplasiaHIVhost cell DNA methylation markershuman papillomavirus

Identifiers

PMID33580586
PMCPMC8564631
OpenAlexW3126837131

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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.