Evidence map›Paper›PMID 25267748›Full record

Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2014

p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma.

Christine H Chung, Qiang Zhang, Christina S Kong, Jonathan Harris, Elana J Fertig, Paul M Harari, Dian Wang, Kevin P Redmond, George Shenouda, Andy Trotti and 4 more

Registry-linked trialAbstract readClinical Trial, Phase IIClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03356223 (A Phase II Trial Aiming to Evaluate the Clinical Interest of ABEMACICLIB Monotherapy in Patients With Locally Advanced/Metastatic Head and Neck Cancer After Failure of Platinum and Cetuximab or Anti-EGFR-based Therapy and Harboring an Homozygous Deletion of CDKN2A, and/or an Amplification of CCND1 and/or of CDK6), which is not on this map. Cited by 190 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
190citing papers in PubMed, 8 pooled it
39.9field-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.

NCT03356223 phase2completednot on this mapstarted 2018, after this paper: background citation

A Phase II Trial Aiming to Evaluate the Clinical Interest of ABEMACICLIB Monotherapy in Patients With Locally Advanced/Metastatic Head and Neck Cancer After Failure of Platinum and Cetuximab or Anti-EGFR-based Therapy and Harboring an Homozygous Deletion of CDKN2A, and/or an Amplification of CCND1 and/or of CDK6

TypeinterventionalSponsorCentre Leon BerardRan2018 to 2022Enrolled25ConditionsHead and Neck Cancer, Advanced Cancer, Metastatic CancerArmsAbemaciclib
3 · Its place in the literature

Who cites it

190 citing papers in PubMed, 8 syntheses or guidelines pooled it, 375 citations in OpenAlex.

  1. Pooled it
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  8. Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status.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 · 2016
    Pooled it
  9. Trial
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  12. Nomogram to Predict the Benefit of Intensive Treatment for Locoregionally Advanced Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
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  17. Article
  18. SRSF3 plays a key role in liver cancer sex disparity by facilitating hepatocyte expression of ERα and FOXA.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  20. Review

130 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Christine H ChungChristine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO. cchung11@jhmi.edu.
Qiang ZhangChristine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.
Christina S KongChristine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.
Jonathan HarrisChristine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.
Elana J FertigChristine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.
Paul M HarariChristine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.
Dian WangChristine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.
Kevin P RedmondChristine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.
George ShenoudaChristine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.
Andy TrottiChristine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.
David RabenChristine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.
Maura L GillisonChristine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.
Richard C JordanChristine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.
Quynh-Thu LeChristine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.
University of Wisconsin Carbone Cancer Center · US

Funding

NRG Oncology Network Group Operations Center - GY9 BIQSFP Reports/BudgetsU10CA180868 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI NORMAN WOLMARK · 2014 to 2026
$206.8M
RTOG Foreign AccrualU10CA021661 · NCI · AMERICAN COLLEGE OF RADIOLOGY · PI CURRAN, WALTER J. · 1985 to 2013
$150.3M
Statistics CoreU10CA180822 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Mei-Yin C Polley · 2014 to 2026
$146.4M
RTOG Foreign AccrualsU10CA037422 · NCI · AMERICAN COLLEGE OF RADIOLOGY · PI BRUNER, DEBORAH WATKINS · 1985 to 2013
$30.4M
NCI NIH HHS U10 CA021661NCI NIH HHS U10 CA037422NCI NIH HHS U10 CA180822NCI NIH HHS U10 CA180868NCI NIH HHS U10 CA21661NCI NIH HHS U10 CA37422
6 · The paper itself

Abstract

purposeAlthough p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been well established in cancer of the oral cavity, hypopharynx, or larynx, collectively referred as non-OPSCC, where HPV infection is less common than in the oropharynx. PATIENTS AND

methodsp16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129, 0234, and 0522 studies were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). Hazard ratios from Cox models were expressed as positive or negative, stratified by trial, and adjusted for clinical characteristics.

resultsp16 expression was positive in 14.1% (12 of 85), 24.2% (23 of 95), and 19.0% (27 of 142) and HPV ISH was positive in 6.5% (six of 93), 14.6% (15 of 103), and 6.9% (seven of 101) of non-OPSCCs from RTOG 0129, 0234, and 0522 studies, respectively. Hazard ratios for p16 expression were 0.63 (95% CI, 0.42 to 0.95; P = .03) and 0.56 (95% CI, 0.35 to 0.89; P = .01) for progression-free (PFS) and overall survival (OS), respectively. Comparing OPSCC and non-OPSCC, patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC, but patients with p16-negative OPSCC and non-OPSCC have similar outcomes.

conclusionSimilar to results in patients with OPSCC, patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC, and HPV may also have a role in outcome in a subset of non-OPSCC. However, further development of a p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting.

Indexed as

Gene Expression Regulation, NeoplasticAntibodies, Monoclonal, HumanizedBiomarkers, TumorCarcinoma, Squamous CellCetuximabCisplatinCyclin-Dependent Kinase Inhibitor p16Disease-Free SurvivalDocetaxelDose Fractionation, RadiationHead and Neck NeoplasmsHumansImmunohistochemistryNeoplasm ProteinsPapillomaviridaePapillomavirus InfectionsAntibodies, Monoclonal, HumanizedBiomarkers, TumorCDKN2A protein, humanCetuximabCisplatinCyclin-Dependent Kinase Inhibitor p16DocetaxelNeoplasm ProteinsTaxoids

Identifiers

PMID25267748
PMCPMC4251957
OpenAlexW1996456132

What OpenQuestion holds

Textmetadata
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Registered trials

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.