Evidence map›Paper›PMID 39936378›Full record

ArticleInternational journal of cancer2025

DNA methylation and copy number alterations in the progression of HPV-associated high-grade vulvar intraepithelial lesion.

Flavia Runello, Aude Jary, Sylvia Duin, Yongsoo Kim, Kahren van Eer, Féline O Voss, Nikki B Thuijs, Maaike C G Bleeker, Renske D M Steenbergen

Abstract read
In one paragraph

Article in International journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Review
  2. 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

9 authors.

Flavia RunelloDepartment of Pathology, Amsterdam UMC, Amsterdam, The Netherlands.ORCID 0009-0005-2638-8343
Aude JaryDepartment of Pathology, Amsterdam UMC, Amsterdam, The Netherlands.
Sylvia DuinDepartment of Pathology, Amsterdam UMC, Amsterdam, The Netherlands.
Yongsoo KimDepartment of Pathology, Amsterdam UMC, Amsterdam, The Netherlands.
Kahren van EerDepartment of Pathology, Amsterdam UMC, Amsterdam, The Netherlands.
Féline O VossDepartment of Pathology, Amsterdam UMC, Amsterdam, The Netherlands.ORCID 0000-0002-9422-4296
Nikki B ThuijsDepartment of Pathology, Amsterdam UMC, Amsterdam, The Netherlands.ORCID 0000-0001-9159-5609
Maaike C G BleekerDepartment of Pathology, Amsterdam UMC, Amsterdam, The Netherlands.
Renske D M SteenbergenDepartment of Pathology, Amsterdam UMC, Amsterdam, The Netherlands.ORCID 0000-0002-2327-9839

Funding

Association pour la Recherche sur le CancerKWF Kankerbestrijding 2016-10382
6 · The paper itself

Abstract

Human papillomavirus (HPV)-associated high-grade vulvar intraepithelial lesion (HSIL) is a precursor of vulvar squamous cell carcinoma (VSCC). Because of the 8% cancer risk, many vulvar HSIL patients undergo aggressive and mutilating treatments. Characterizing HSIL by their progression risk can help individualize treatment strategies. Accordingly, copy number alterations (CNAs) and DNA methylation have been identified as biomarkers for cancer risk stratification of HSIL. Here, we assessed their potential correlation, and relation to HPV16 (sub)lineages and progression to vulvar cancer. Eighty-two vulvar formalin-fixed paraffin-embedded (FFPE) samples, including controls, HSIL, HSIL adjacent to VSCC and VSCC, with previously determined DNA methylation profiles, were analysed for CNAs using mFAST-SeqS. Genome-wide z-scores were calculated to determine overall aneuploidy (aneuploidy scores), and compared to the methylation levels and status of marker panel ZNF582/SST/miR124-2. For 52 HPV16-positive cases, HPV (sub)lineages were determined by Sanger sequencing. HPV16 lineage A was predominant (86.4%), followed equally by lineages B, C, and D. Frequent chromosomal alterations included chr1pq, chr3q, chr9q gains, and chr2q, chr4q losses. Median aneuploidy scores increased across disease categories, from 0 in controls, to 3 in HSIL, 16 in HSIL adjacent to VSCC and 29 in VSCC. A positive relationship between aneuploidy scores and DNA methylation levels was found (ρ = 0.61, Spearman's rank correlation test). Aneuploidy scores were significantly higher in methylation-positive samples (p < .001). In conclusion, we showed that DNA methylation and CNAs both rise with increasing severity of disease, indicating their prognostic value for cancer risk stratification of HSIL, while no relation to HPV16 (sub)lineages was found.

Indexed as

Carcinoma, Squamous CellDNA Copy Number VariationsDNA MethylationHuman papillomavirus 16Papillomavirus InfectionsVulvar NeoplasmsAdultAgedBiomarkers, TumorDisease ProgressionFemaleHumansMiddle AgedBiomarkers, Tumorcopy number alterationsDNA methylationhigh‐grade vulvar intraepithelial lesionmFAST‐SeqS

Identifiers

PMID39936378
PMCPMC11924301

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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.