Evidence map›Paper›PMID 32266940›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2021

Cancer Risk Stratification of Anal Intraepithelial Neoplasia in Human Immunodeficiency Virus-Positive Men by Validated Methylation Markers Associated With Progression to Cancer.

Ramon P van der Zee, Olivier Richel, Carel J M van Noesel, Iuliana Ciocănea-Teodorescu, Annina P van Splunter, Timo J Ter Braak, Mayura Nathan, Tamzin Cuming, Michael Sheaff, Alexander Kreuter and 5 more

Abstract read
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
–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

24 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. German-Austrian guideline on screening for anal dysplasia and anal carcinoma in people living with HIV.Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG · 2025
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  5. International journal of molecular sciences · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Ramon P van der ZeeDepartment of Pathology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Olivier RichelDepartment of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Carel J M van NoeselDepartment of Pathology, Amsterdam University Medical Centers, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Iuliana Ciocănea-TeodorescuDepartment of Epidemiology and Biostatistics, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands.
Annina P van SplunterDepartment of Pathology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Timo J Ter BraakDepartment of Pathology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Mayura NathanHomerton Anal Neoplasia Service, Homerton University Hospital, London, United Kingdom.
Tamzin CumingHomerton Anal Neoplasia Service, Homerton University Hospital, London, United Kingdom.
Michael SheaffDepartment of Cellular Pathology, Barts Health National Health Service (NHS) Trust, London, United Kingdom.
Alexander KreuterDepartment of Dermatology, Venerology, and Allergology, Helios St Elisabeth Hospital Oberhausen, University Witten/Herdecke, Oberhausen, Germany.
Chris J L M MeijerDepartment of Pathology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Wim G V QuintDDL Diagnostic Laboratory, Rijswijk, The Netherlands.
Henry J C de VriesDepartment of Dermatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
Jan M PrinsDepartment of Internal Medicine, Division of Infectious Diseases, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Institute for Infection and Immunity (AI&II), Amsterdam, The Netherlands.
Renske D M SteenbergenDepartment of Pathology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0002-2327-9839

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHigh-grade anal intraepithelial neoplasia (HGAIN; AIN2-3) is highly prevalent in HIV+ men, but only a minority of these lesions progress towards cancer. Currently, cancer progression risk cannot be established; therefore, no consensus exists on whether HGAIN should be treated. This study aimed to validate previously identified host cell DNA methylation markers for detection and cancer risk stratification of HGAIN.

methodsA large independent cross-sectional series of 345 anal cancer, AIN3, AIN2, AIN1, and normal control biopsies of HIV+ men was tested for DNA methylation of 6 genes using quantitative methylation-specific PCR. We determined accuracy for detection of AIN3 and cancer (AIN3+) by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Methylation levels were assessed in a series of 10 anal cancer cases with preceding HGAIN at similar anatomic locations, and compared with the cross-sectional series.

resultsMethylation levels of all genes increased with increasing severity of disease (P < .05). HGAIN revealed a heterogeneous methylation pattern, with a subset resembling cancer. ZNF582 showed highest accuracy (AUC = 0.88) for AIN3+ detection, slightly improved by addition of ASCL1 and SST (AUC = 0.89), forming a marker panel. In the longitudinal series, HGAIN preceding cancer displayed high methylation levels similar to cancers.

conclusionsWe validated the accuracy of 5 methylation markers for the detection of anal (pre-) cancer. High methylation levels in HGAIN were associated with progression to cancer. These markers provide a promising tool to identify HGAIN in need of treatment, preventing overtreatment of HGAIN with a low cancer progression risk.

Indexed as

Anus NeoplasmsCarcinoma in SituHIV InfectionsPapillomavirus InfectionsCross-Sectional StudiesHIVHomosexuality, MaleHumansMaleRisk Assessmentanal canceranal intraepithelial neoplasiaHIVhost cell DNA methylation markershuman papillomavirus

Identifiers

PMID32266940
PMCPMC8204787

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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.