Evidence map›Paper›PMID 22743284›Full record

ArticleThe American journal of surgical pathology2012

Validation of methods for oropharyngeal cancer HPV status determination in US cooperative group trials.

Richard C Jordan, Mark W Lingen, Bayardo Perez-Ordonez, Xin He, Robert Pickard, Michael Koluder, Bo Jiang, Paul Wakely, Weihong Xiao, Maura L Gillison

Abstract readValidation Study
In one paragraph

Article in The American journal of surgical pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed, 7 pooled it
–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

168 citing papers in PubMed, 7 syntheses or guidelines pooled it.

  1. Pooled it
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  6. The prevalence of human papillomavirus in pediatric tonsils: a systematic review of the literature.Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale · 2018
    Pooled it
  7. Pooled it
  8. Trial
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  10. Reduced-Dose Radiation Therapy for HPV-Associated Oropharyngeal Carcinoma (NRG Oncology HN002).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021
    Trial
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  19. p16 protein expression and human papillomavirus status as prognostic biomarkers of nonoropharyngeal head and neck squamous cell carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2014
    Trial
  20. Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2014
    Trial

108 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

10 authors.

Richard C JordanDepartments of Orofacial Sciences, Pathology & Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Mark W Lingen
Bayardo Perez-Ordonez
Xin He
Robert Pickard
Michael Koluder
Bo Jiang
Paul Wakely
Weihong Xiao
Maura L Gillison

Funding

Oral HPV Infection in HIV-Infected Men and WomenR01DE016631 · NIDCR · OHIO STATE UNIVERSITY · PI GILLISON, MAURA L · 2005 to 2008
$2.5M
DDS Master's in Clinical Research (DDS-MCR)T32DE019096 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JORDAN, RICHARD C · 2008 to 2012
$313k
NIDCR NIH HHS DE016631NIDCR NIH HHS R01 DE016631NIDCR NIH HHS T32 DE019096
6 · The paper itself

Abstract

Tumor human papillomavirus (HPV) status is a prognostic factor for oropharyngeal cancer, but classification methods are not standardized. Here we validate the HPV classification methods used in US cooperative group trials. Tumor DNA and RNA purified from 240 paraffin-embedded oropharyngeal cancers diagnosed from 2000 to 2009 were scored as evaluable if positive for DNA and mRNA controls by quantitative polymerase chain reaction (PCR). Eighteen high-risk (HR) HPV types were detected in tumors by consensus PCR, followed by HR-HPV E6/7 oncogene expression analysis by quantitative reverse transcriptase PCR. The sensitivity (S), specificity (SP), and positive (PPV) and negative predictive values (NPV) of p16 expression detected by immunohistochemistry (IHC) and HPV16 detected by in situ hybridization (ISH) were evaluated in comparison with HR-HPV E6/7 oncogene expression. Interrater agreement among 3 pathologists was evaluated by κ statistics. Of 235 evaluable tumors, 158 (67%; 95% confidence interval, 61.2-73.3) were positive for HR-HPV E6/7 oncogene expression [HPV type 16 (92%), 18 (3%), 33 (3%), 35 (1%), or 58 (1%)]. p16 IHC had high sensitivity (S 96.8%, SP 83.8%, PPV 92.7%, and NPV 92.5%), whereas HPV16 ISH had high specificity (S 88.0%, SP 94.7%, PPV 97.2%, and NPV 78.9%) for HR-HPV oncogene expression. Interrater agreement was excellent for p16 (κ=0.95 to 0.98) and HPV16 ISH (κ=0.83 to 0.91). Receiver operating curve analysis determined the cross-product of p16 intensity score and percentage of tumor staining to optimally discriminate HR-HPV E6/7-positive and HR-HPV E6/7-negative tumors. p16 IHC and HPV16 ISH assays show excellent performance, with high sensitivity and specificity, respectively. A new validated H-score for p16 IHC assessment is proposed. Appropriate assay choice depends on clinical implications of a false-positive or false-negative test.

Indexed as

Biomarkers, TumorCarcinoma, Squamous CellChi-Square DistributionClinical Trials as TopicCooperative BehaviorCyclin-Dependent Kinase Inhibitor p16DNA, ViralFalse Negative ReactionsFalse Positive ReactionsFeasibility StudiesFemaleFixativesFormaldehydeHuman papillomavirus 16HumansImmunohistochemistryBiomarkers, TumorCyclin-Dependent Kinase Inhibitor p16DNA, ViralE6 protein, Human papillomavirus type 16FixativesFormaldehydeoncogene protein E7, Human papillomavirus type 16Oncogene Proteins, ViralPapillomavirus E7 ProteinsRepressor ProteinsRNA, MessengerRNA, Viral

Identifiers

PMID22743284
PMCPMC6362985

What OpenQuestion holds

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LicenceTDM
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.