Evidence map›Paper›PMID 35686306›Full record

ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2023

FAM19A4/miR124-2 Methylation Testing and Human Papillomavirus (HPV) 16/18 Genotyping in HPV-Positive Women Under the Age of 30 Years.

Frederique J Vink, Chris J L M Meijer, Albertus T Hesselink, Arno N Floore, Birgit I Lissenberg-Witte, Jesper H Bonde, Helle Pedersen, Kate Cuschieri, Ramya Bhatia, Mario Poljak and 8 more

Open access · bronzeAbstract readMulticenter Study
In one paragraph

Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 2 pooled it
3.6field-weighted citation impact, top 6% 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

20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 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

18 authors at 9 institutions in 6 countries.

Frederique J VinkAmsterdam University Medical Center, Vrije Universiteit Amsterdam, Pathology, Amsterdam, the Netherlands.ORCID 0000-0002-4951-9167
Chris J L M MeijerAmsterdam University Medical Center, Vrije Universiteit Amsterdam, Pathology, Amsterdam, the Netherlands.ORCID 0000-0002-2758-9463
Albertus T HesselinkSelf-screen B.V., Amsterdam, The Netherlands.ORCID 0000-0002-4282-4417
Arno N FlooreSelf-screen B.V., Amsterdam, The Netherlands.ORCID 0000-0002-5835-2688
Birgit I Lissenberg-WitteAmsterdam University Medical Center, Vrije Universiteit Amsterdam, Epidemiology and Data Science, Amsterdam, the Netherlands.ORCID 0000-0001-9448-1826
Jesper H BondeMolecular Pathology Laboratory, Department of Pathology, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark.ORCID 0000-0003-4853-6747
Helle PedersenMolecular Pathology Laboratory, Department of Pathology, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark.
Kate CuschieriScottish HPV Reference Laboratory, Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, Scotland.ORCID 0000-0002-2604-3928
Ramya BhatiaScottish HPV Reference Laboratory, Royal Infirmary of Edinburgh, NHS Lothian, Edinburgh, Scotland.ORCID 0000-0001-5294-0668
Mario PoljakInstitute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.ORCID 0000-0002-3216-7564
Anja Oštrbenk ValenčakInstitute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.ORCID 0000-0002-3061-5319
Peter HillemannsDepartment of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.ORCID 0000-0001-9829-3531
Wim G V QuintDDL Diagnostic Laboratory, Rijswijk, The Netherlands.
Marta Del PinoInstitut Clinic of Gynecology, Obstetrics and Neonatology, Gynecology Oncology Unit, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Faculty of Medicine, University of Barcelona, Barcelona, Spain.ORCID 0000-0003-2178-2403
Gemma G KenterCenter for Gynecologic Oncology Amsterdam, Amsterdam University Medical Center and Netherlands Cancer Institute, Amsterdam, The Netherlands.ORCID 0000-0002-7284-3918
Renske D M SteenbergenAmsterdam University Medical Center, Vrije Universiteit Amsterdam, Pathology, Amsterdam, the Netherlands.ORCID 0000-0002-2327-9839
Daniëlle A M HeidemanAmsterdam University Medical Center, Vrije Universiteit Amsterdam, Pathology, Amsterdam, the Netherlands.ORCID 0000-0001-6463-7391
Maaike C G BleekerAmsterdam University Medical Center, Vrije Universiteit Amsterdam, Pathology, Amsterdam, the Netherlands.ORCID 0000-0001-9610-8064
Amsterdam University Medical Centers · NLHvidovre Hospital · DKNHS Lothian · GBUniversity of Ljubljana · SIDDL Diagnostic Laboratory · NLMedizinische Hochschule Hannover · DEThe Netherlands Cancer Institute · NLUniversitat de Barcelona · ESVrije Universiteit Amsterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHigh-grade squamous intraepithelial lesions (HSIL) or cervical intraepithelial neoplasia (CIN) grade 2/3 lesions in human papillomavirus (HPV)-positive women <30 years of age have high spontaneous regression rates. To reduce overtreatment, biomarkers are needed to delineate advanced CIN lesions that require treatment. We analyzed the FAM19A4/miR124-2 methylation test and HPV16/18 genotyping in HPV-positive women aged <30 years, aiming to identify CIN2/3 lesions in need of treatment.

methodsA European multicenter retrospective study was designed evaluating the FAM19A4/miR124-2 methylation test and HPV16/18 genotyping in cervical scrapes of 1061 HPV-positive women aged 15-29 years (690 ≤CIN1, 166 CIN2, and 205 CIN3+). A subset of 62 CIN2 and 103 CIN3 were immunohistochemically characterized by HPV E4 expression, a marker for a productive HPV infection, and p16ink4a and Ki-67, markers indicative for a transforming infection. CIN2/3 lesions with low HPV E4 expression and high p16ink4a/Ki-67 expression were considered as nonproductive, transforming CIN, compatible with advanced CIN2/3 lesions in need of treatment.

resultsFAM19A4/miR124-2 methylation positivity increased significantly with CIN grade and age groups (<25, 25-29, and ≥30 years), while HPV16/18 positivity was comparable across age groups. FAM19A4/miR124-2 methylation positivity was HPV type independent. Methylation-positive CIN2/3 lesions had higher p16ink4a/Ki-67-immunoscores (P = .003) and expressed less HPV E4 (P = .033) compared with methylation-negative CIN2/3 lesions. These differences in HPV E4 and p16ink4a/Ki-67 expression were not found between HPV16/18-positive and non-16/18 HPV-positive lesions.

conclusionsCompared with HPV16/18 genotyping, the FAM19A4/miR124-2 methylation test detects nonproductive, transforming CIN2/3 lesions with high specificity in women aged <30 years, providing clinicians supportive information about the need for treatment of CIN2/3 in young HPV-positive women.

Indexed as

MicroRNAsPapillomavirus InfectionsUterine Cervical DysplasiaUterine Cervical NeoplasmsAdultCytokinesDNA MethylationFemaleGenotypeHuman papillomavirus 16Human papillomavirus 18Human Papillomavirus VirusesHumansKi-67 AntigenPapillomaviridaeRetrospective StudiesCytokinesKi-67 AntigenMicroRNAsMIRN124 microRNA, humanTAFA4 protein, humancervical cancercervical intraepithelial neoplasiahost cell DNA methylationHPV E4human papillomavirusp16ink4a/Ki-67 immunoscore

Identifiers

PMID35686306
PMCPMC9907535
OpenAlexW4281690624

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.