Evidence map›Paper›PMID 25082736›Full record

ArticleInternational journal of cancer2015

Viral load, gene expression and mapping of viral integration sites in HPV16-associated HNSCC cell lines.

Nadine C Olthof, Christian U Huebbers, Jutta Kolligs, Mieke Henfling, Frans C S Ramaekers, Iris Cornet, Josefa A van Lent-Albrechts, Alexander P A Stegmann, Steffi Silling, Ulrike Wieland and 8 more

Open access · greenAbstract read
In one paragraph

Article in International journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
8.2field-weighted citation impact, top 2% 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

65 citing papers in PubMed, 121 citations in OpenAlex.

  1. Article
  2. Article
  3. HPV Integration in Head and Neck Cancer: Downstream Splicing Events and Expression Ratios Linked with Poor Outcomes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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5 more citing papers are in PubMed but not listed here.

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 8 institutions in 4 countries.

Nadine C OlthofDepartment of Otorhinolaryngology and Head and Neck Surgery, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands; Department of Molecular Cell Biology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
Christian U Huebbers
Jutta Kolligs
Mieke Henfling
Frans C S Ramaekers
Iris Cornet
Josefa A van Lent-Albrechts
Alexander P A Stegmann
Steffi Silling
Ulrike Wieland
Thomas E Carey
Heather M Walline
Susanne M Gollin
Thomas K Hoffmann
Johan de Winter
Bernd Kremer
Jens P Klussmann
Ernst-Jan M Speel
Maastricht University Medical Centre · NLLaboratoire National de Référence · MAUniversity of Cologne · DEUniversity of Michigan–Ann Arbor · USAmsterdam UMC Location VUmc · NLUniversitätsklinikum Gießen und Marburg · DEUniversity Hospital Ulm · DEUPMC Hillman Cancer Center · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2M
Therapeutic Potential and Mechanism of Action of Potent Small Molecule InhibitorsP50CA097248 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WOLF, GREGORY T · 2002 to 2013
$25.3M
Training Program in Tumor MicroenvironmentT32CA009676 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro, Analisa Virginia DiFeo · 1992 to 2026
$7.3M
Biomarkers to Guide Treatment and Improve Survival in Oral/Oropharyngeal CancerR01DE019126 · NIDCR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CAREY, THOMAS E. · 2009 to 2012
$1.4M
NCI NIH HHS P30 CA046592NCI NIH HHS P50 CA097248NCI NIH HHS T32 CA009676NIDCR NIH HHS R01 DE019126
6 · The paper itself

Abstract

HPV-related HNSCC generally have a better prognosis than HPV-negative HNSCC. However, a subgroup of HPV-positive tumors with poor prognosis has been recognized, particularly related to smoking, EGFR overexpression and chromosomal instability. Viral integration into the host genome might contribute to carcinogenesis, as is shown for cervical carcinomas. Therefore, all HPV16-positive HNSCC cell lines currently available have been carefully analyzed for viral and host genome parameters. The viral integration status, viral load, viral gene expression and the presence of aneusomies was evaluated in the cell lines UD-SCC-2, UM-SCC-047, UM-SCC-104, UPCI:SCC090, UPCI:SCC152, UPCI:SCC154 and 93VU147T. HPV integration was examined using FISH, APOT-PCR and DIPS-PCR. Viral load and the expression of the viral genes E2, E6 and E7 were determined via quantitative PCR. All cell lines showed integration-specific staining patterns and signals indicating transcriptional activity using FISH. APOT- and DIPS-PCR identified integration-derived fusion products in six cell lines and only episomal products for UM-SCC-104. Despite the observed differences in viral load and the number of viral integration sites, this did not relate to the identified viral oncogene expression. Furthermore, cell lines exhibited EGFR expression and aneusomy (except UPCI:SCC154). In conclusion, all HPV16-positive HNSCC cell lines showed integrated and/or episomal viral DNA that is transcriptionally active, although viral oncogene expression was independent of viral copy number and the number of viral integration sites. Because these cell lines also contain EGFR expression and aneusomy, which are parameters of poor prognosis, they should be considered suitable model systems for the development of new antiviral therapies.

Indexed as

Viral LoadCarcinoma, Squamous CellDNA, ViralErbB ReceptorsFemaleGene Expression ProfilingHead and Neck NeoplasmsHuman papillomavirus 16HumansImmunoenzyme TechniquesIn Situ Hybridization, FluorescenceMaleMiddle AgedOncogene Proteins, ViralPapillomavirus InfectionsPolymerase Chain ReactionDNA, ViralEGFR protein, humanErbB ReceptorsOncogene Proteins, ViralAPOT-PCRDIPS-PCRgenetic localizationintegrationviral integration

Identifiers

PMID25082736
PMCPMC5370555
OpenAlexW1773758992

What OpenQuestion holds

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Read underepoch 390

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.