Evidence map›Paper›PMID 33634865›Full record

ArticleInternational journal of cancer2021

The unveiled reality of human papillomavirus as risk factor for oral cavity squamous cell carcinoma.

Irene H Nauta, Daniëlle A M Heideman, Arjen Brink, Berdine van der Steen, Elisabeth Bloemena, Senada Koljenović, Robert J Baatenburg de Jong, C René Leemans, Ruud H Brakenhoff

Open access · bronzeAbstract readComparative StudyMulticenter Study
In one paragraph

Article in International journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 4 pooled it
10.6field-weighted citation impact, top 1% 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

43 citing papers in PubMed, 4 syntheses or guidelines pooled it, 73 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Human papillomavirus infection and non-oropharyngeal head and neck cancers: an umbrella review of meta-analysis.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2023
    Pooled it
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  6. Effect of metformin on hypoxia-associated gene expression in oral cavity squamous cell carcinoma in non-diabetic patients - a prospective window of opportunity study.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 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

9 authors at 4 institutions in 1 country.

Irene H NautaAmsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0003-0318-715X
Daniëlle A M HeidemanAmsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Arjen BrinkAmsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Berdine van der SteenDepartment of Otorhinolaryngology/Head and Neck Surgery, Erasmus Medical Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Elisabeth BloemenaAmsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Senada KoljenovićDepartment of Pathology, Erasmus Medical Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Robert J Baatenburg de JongDepartment of Otorhinolaryngology/Head and Neck Surgery, Erasmus Medical Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
C René LeemansAmsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Ruud H BrakenhoffAmsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0003-3251-5378
Amsterdam Neuroscience · NLErasmus MC Cancer Institute · NLAcademic Center for Dentistry Amsterdam · NLAmsterdam University Medical Centers · NL

Funding

Horizon 2020 Framework Programme Grant Agreement 689715 BD2Decide
6 · The paper itself

Abstract

The prognostic impact of human papillomavirus (HPV) in oropharyngeal cancer is generally acknowledged, and HPV-status is assessed routinely in clinical practice. Paradoxically, while the oral cavity seems the predilection site for productive HPV-infections, figures on HPV-attribution in oral cavity squamous cell carcinoma (OCSCC) differ widely, and prognostic impact is uncertain. Major obstacles are the lack of reproducible assays to detect HPV in nonoropharyngeal cancers, the relatively small cohorts studied and consequently the shortfall of convincing data. In our study, we used a validated, nucleic acid-based workflow to assess HPV-prevalence in a consecutive cohort of 1016 OCSCCs, and investigated its prognostic impact. In parallel, we analyzed p16-immunohistochemistry (p16-IHC) as surrogate marker for transforming HPV-infection and independent prognosticator. All OCSCC-patients diagnosed between 2008 and 2014 at two Dutch university medical centers were included (N = 1069). Formalin-fixed, paraffin-embedded (FFPE)-samples of 1016 OCSCCs could be retrieved. Punch biopsies were taken from the tumor area in the FFPE-blocks and tested for HPV. P16-IHC was performed on 580 OCSCCs, including all HPV-positive tumors. From 940 samples (92.5%), nucleic acids were of sufficient quality for HPV-testing. In total, 21 (2.2%) OCSCCs were HPV DNA-positive. All HPV DNA-positive tumors were E6 mRNA-positive and considered as true HPV-positive. There was no difference in survival between HPV-positive and HPV-negative OCSCCs. In total, 46 of 580 (7.9%) OCSCCs were p16-immunopositive, including all HPV-positive tumors. Survival was comparable in p16-positive and p16-negative OCSCCs. To conclude, HPV-prevalence is very low in OCSCC and neither HPV-status nor p16-status affects outcome. Based on these data, determining HPV-status in OCSCC seems irrelevant for clinical management.

Indexed as

AgedCarcinoma, Squamous CellCyclin-Dependent Kinase Inhibitor p16FemaleHuman papillomavirus 16HumansMaleMiddle AgedMouth NeoplasmsOncogene Proteins, ViralPapillomavirus InfectionsPrevalencePrognosisRepressor ProteinsSex CharacteristicsSurvival AnalysisCDKN2A protein, humanCyclin-Dependent Kinase Inhibitor p16E6 protein, Human papillomavirus type 16Oncogene Proteins, ViralRepressor Proteinshuman papillomavirusoral cavity squamous cell carcinomap16-immunohistochemistryprevalenceprognosis

Identifiers

PMID33634865
PMCPMC8251537
OpenAlexW3132898342

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.