Evidence map›Paper›PMID 31302935›Full record

ArticleThe British journal of dermatology2020

Grading immunohistochemical markers p16

A Leeman, D Jenkins, E Marra, M van Zummeren, E C Pirog, M M van de Sandt, A van Eeden, M F Schim van der Loeff, J Doorbar, H J C de Vries and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in The British journal of dermatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. HPV in oropharyngeal squamous papillomas: a missing link in head and neck viral pathogenesis.Virchows Archiv : an international journal of pathology · 2026
    Article
  2. Prevalence of the most common types of high-risk HPV and p16Postepy dermatologii i alergologii · 2026
    Article
  3. Article
  4. p16International journal of cancer · 2025
    Article
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  10. Review
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  14. Different patterns of p16INK4a immunohistochemical expression and their biological implications in laryngeal squamous cell carcinoma.Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie
    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

13 authors at 6 institutions in 3 countries.

A LeemanDDL Diagnostic Laboratory, Visseringlaan 25, 2288 ER, Rijswijk, the Netherlands.ORCID 0000-0002-5882-7778
D JenkinsDDL Diagnostic Laboratory, Visseringlaan 25, 2288 ER, Rijswijk, the Netherlands.
E MarraPublic Health Service of Amsterdam, Department of Infectious Diseases, Amsterdam, the Netherlands.
M van ZummerenCancer Center Amsterdam, Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.
E C PirogDepartment of Pathology, Weill Cornell Medical College, New York, NY, U.S.A.
M M van de SandtDDL Diagnostic Laboratory, Visseringlaan 25, 2288 ER, Rijswijk, the Netherlands.
A van EedenDepartment of Internal Medicine, DC Klinieken, Amsterdam, the Netherlands.
M F Schim van der LoeffPublic Health Service of Amsterdam, Department of Infectious Diseases, Amsterdam, the Netherlands.
J DoorbarDepartment of Pathology, University of Cambridge, Cambridge, U.K.
H J C de VriesPublic Health Service of Amsterdam, Department of Infectious Diseases, Amsterdam, the Netherlands.
F J van KemenadeErasmus MC University Medical Center, Department of Pathology, Rotterdam, the Netherlands.
C J L M MeijerCancer Center Amsterdam, Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.
W G V QuintDDL Diagnostic Laboratory, Visseringlaan 25, 2288 ER, Rijswijk, the Netherlands.
DDL Diagnostic Laboratory · NLGGD Amsterdam · NLAmsterdam UMC Location Vrije Universiteit Amsterdam · NLCornell University · USErasmus MC · NLUniversity of Cambridge · GB

Funding

Cancer Research UK 28754Medical Research Council MC_PC_13050Medical Research Council MR/S024409/1
6 · The paper itself

Abstract

objectivesBecause current guidelines recognise high-grade anal squamous intraepithelial lesions (HSILs) and low-grade SILs (LSILs), and recommend treatment of all HSILs although not all progress to cancer, this study aims to distinguish transforming and productive HSILs by grading immunohistochemical (IHC) biomarkers p16

methodsImmunostaining for p16 and HPV E4 was performed and graded in 183 biopsies from 108 HIV-positive men who have sex with men. The causative HPV genotype of the worst lesion was identified using the HPV SPF10-PCR-DEIA-LiPA25 version 1 system, with laser capture microdissection for multiple infections. The worst lesions were scored for p16 (0-4) to identify activity of the hrHPV E7 gene, and panHPV E4 (0-2) to mark HPV production and life cycle completion.

resultsThere were 37 normal biopsies, 60 LSILs and 86 HSILs, with 85% of LSILs caused by lrHPV and 93% of HSILs by hrHPV. No normal biopsy showed E4, but 43% of LSILs and 37% of HSILs were E4 positive. No differences in E4 positivity rates were found between lrHPV and hrHPV lesions. Most of the lesions caused by lrHPV (90%) showed very extensive patchy p16 staining; p16 grade in HSILs was variable, with frequency of productive HPV infection dropping with increasing p16 grade.

conclusionsCombined p16/E4 IHC identifies productive and nonproductive HSILs associated with hrHPV within the group of HSILs defined by the Lower Anogenital Squamous Terminology recommendations. This opens the possibility of investigating selective treatment of advanced transforming HSILs caused by hrHPV, and a 'wait and see' policy for productive HSILs. What's already known about this topic? For preventing anal cancer in high-risk populations, all patients with high-grade squamous intraepithelial lesions (HSILs) are treated, even though this group of lesions is heterogeneous, the histology is variable and regression is frequent. What does this study add? By adding human papillomavirus (HPV) E4 immunohistochemistry to p16

Indexed as

AlphapapillomavirusPapillomavirus InfectionsSexual and Gender MinoritiesSquamous Intraepithelial LesionsBiomarkers, TumorCyclin-Dependent Kinase Inhibitor p16Homosexuality, MaleHumansMalePapillomaviridaeBiomarkers, TumorCyclin-Dependent Kinase Inhibitor p16

Identifiers

PMID31302935
PMCPMC7187351
OpenAlexW2957651198

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.