Evidence map›Paper›PMID 24586376›Full record

ArticlePloS one2014

Comprehensive analysis of HPV16 integration in OSCC reveals no significant impact of physical status on viral oncogene and virally disrupted human gene expression.

Nadine C Olthof, Ernst-Jan M Speel, Jutta Kolligs, Annick Haesevoets, Mieke Henfling, Frans C S Ramaekers, Simon F Preuss, Uta Drebber, Ulrike Wieland, Steffi Silling and 5 more

Abstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing 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

48 citing papers in PubMed.

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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

15 authors.

Nadine C OlthofDepartment of Otorhinolaryngology and Head and Neck Surgery, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands ; Department of Molecular Cell Biology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
Ernst-Jan M SpeelDepartment of Molecular Cell Biology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands ; Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
Jutta KolligsJean-Uhrmacher-Institute for Otorhinolaryngological Research, University of Cologne, Cologne, Germany.
Annick HaesevoetsDepartment of Molecular Cell Biology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
Mieke HenflingDepartment of Molecular Cell Biology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
Frans C S RamaekersDepartment of Molecular Cell Biology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
Simon F PreussDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Cologne, Cologne, Germany.
Uta DrebberInstitute for Pathology, University Hospital of Cologne, Cologne, Germany.
Ulrike WielandInstitute of Virology, National Reference Centre for Papilloma- and Polyomaviruses, University Hospital of Cologne, Cologne, Germany.
Steffi SillingInstitute of Virology, National Reference Centre for Papilloma- and Polyomaviruses, University Hospital of Cologne, Cologne, Germany.
Wan L LamDepartment of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, Canada.
Emily A VucicDepartment of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, Canada.
Bernd KremerDepartment of Otorhinolaryngology and Head and Neck Surgery, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.
Jens-P KlussmannDepartment of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Giessen, Giessen, Germany.
Christian U HuebbersJean-Uhrmacher-Institute for Otorhinolaryngological Research, University of Cologne, Cologne, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Infection with high-risk human papillomavirus (HPV) type 16 is an independent risk factor for the development of oropharyngeal squamous cell carcinomas (OSCC). However, it is unclear whether viral integration is an essential hallmark in the carcinogenic process of OSCC and whether HPV integration correlates with the level of viral gene transcription and influences the expression of disrupted host genes. We analyzed 75 patients with OSCC. HPV16-positivity was proven by p16(INK4A) immunohistochemistry, PCR and FISH. Viral integration was examined using DIPS- as well as APOT-PCR. Viral E2, E6 and E7 gene expression levels were quantified by quantitative reverse transcriptase (RT-q)PCR. Expression levels of 7 human genes disrupted by the virus were extracted from mRNA expression profiling data of 32 OSCCs. Viral copy numbers were assessed by qPCR in 73 tumors. We identified 37 HPV16-human fusion products indicating viral integration in 29 (39%) OSCC. In the remaining tumors (61%) only episome-derived PCR products were detected. When comparing OSCC with or without an integration-derived fusion product, we did not find significant differences in the mean RNA expression of viral genes E2, E6 and E7 or the viral copy numbers per cell, nor did the RNA expression of the HPV-disrupted genes differ from either group of OSCC. In conclusion, our data do not support the hypothesis that integration affects the levels of viral and/or HPV-disrupted human gene transcripts. Thus constitutive, rather than a high level, of expression of oncogene transcripts appears to be required in HPV-related OSCC.

Indexed as

AdultAgedAged, 80 and overCarcinoma, Squamous CellDNA, ViralFemaleGene ExpressionGenes, ViralHuman papillomavirus 16HumansMaleMiddle AgedOncogene Proteins, ViralOropharyngeal NeoplasmsPapillomavirus E7 ProteinsPapillomavirus InfectionsDNA, ViralOncogene Proteins, ViralPapillomavirus E7 ProteinsRNA, MessengerRNA, Viral

Identifiers

PMID24586376
PMCPMC3933331

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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.