Evidence map›Paper›PMID 23749640›Full record

ArticleCancer research2013

Enhanced radiation sensitivity in HPV-positive head and neck cancer.

Randall J Kimple, Molly A Smith, Grace C Blitzer, Alexandra D Torres, Joshua A Martin, Robert Z Yang, Chimera R Peet, Laurel D Lorenz, Kwangok P Nickel, Aloysius J Klingelhutz and 2 more

Open access · greenAbstract read
In one paragraph

Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 227 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
227citing papers in PubMed, 4 pooled it
28.3field-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

227 citing papers in PubMed, 4 syntheses or guidelines pooled it, 370 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Hypoxia-Directed Treatment of Human Papillomavirus-Related Oropharyngeal Carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024
    Trial
  6. Early HPV ctDNA Kinetics and Imaging Biomarkers Predict Therapeutic Response in p16+ Oropharyngeal Squamous Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
  7. Trial
  8. 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
  9. Trial
  10. Trial
  11. Trial
  12. Article
  13. Pretreatment Chromosomal Instability Correlates With Radiation Sensitivity in Squamous Cell Cancers.International journal of radiation oncology, biology, physics · 2026
    Article
  14. Review
  15. Article
  16. Genomic Enrichment and Functional Impact of TP53 and CYLD Alterations in Recurrent and Metastatic HPV-Associated Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Article
  17. Article
  18. Article
  19. Article
  20. Article

167 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

12 authors at 3 institutions in 1 country.

Randall J KimpleDepartment of Human Oncology, University of Wisconsin Comprehensive Cancer Center, 3107 WIMR, 1111 Highland Avenue, Madison, WI 53705, USA. rkimple@humonc.wisc.edu
Molly A Smith
Grace C Blitzer
Alexandra D Torres
Joshua A Martin
Robert Z Yang
Chimera R Peet
Laurel D Lorenz
Kwangok P Nickel
Aloysius J Klingelhutz
Paul F Lambert
Paul M Harari
University of Iowa · USUniversity of Wisconsin Carbone Cancer Center · USUniversity of Wisconsin–Madison · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI AMY TRENTHAM-DIETZ · 1985 to 2026
$142.6M
Training in Cancer Biology Training GrantT32CA009135 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI SUGDEN, WILLIAM M. · 1985 to 2024
$10.4M
Virology Training ProgramT32AI078985 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI LAMBERT, PAUL F. · 2009 to 2018
$3.3M
Mouse Model for Human Papillomaviral (HPV)-associated Oral CancerR01DE017315 · NIDCR · UNIVERSITY OF WISCONSIN-MADISON · PI LAMBERT, PAUL F. · 2006 to 2010
$1.7M
EGFR/Radiation Responses and Resistance InteractionsR01CA113448 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI HARARI, PAUL M · 2006 to 2010
$1.3M
Head and Neck squamous cell carcinoma radiation response modulation by HPVR00CA160639 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI KIMPLE, RANDALL J. · 2013 to 2015
$725k
Head and Neck squamous cell carcinoma radiation response modulation by HPVK99CA160639 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI KIMPLE, RANDALL J. · 2011 to 2012
$298k
NCI NIH HHS K99 CA160639NCI NIH HHS P30 CA014520NCI NIH HHS R00 CA160639NCI NIH HHS R01 CA 113448NCI NIH HHS R01 CA113448NCI NIH HHS T32 CA009135NIAID NIH HHS T32 AI078985NIDCR NIH HHS R01 DE017315
6 · The paper itself

Abstract

Patients with human papillomavirus (HPV+)-associated head and neck cancer (HNC) show significantly improved survival outcome compared with those with HPV-negative (HPV-) tumors. Published data examining this difference offers conflicting results to date. We systematically investigated the radiation sensitivity of all available validated HPV+ HNC cell lines and a series of HPV- HNC cell lines using in vitro and in vivo techniques. HPV+ HNCs exhibited greater intrinsic radiation sensitivity (average SF2 HPV-: 0.59 vs. HPV+: 0.22; P < 0.0001), corresponding with a prolonged G2-M cell-cycle arrest and increased apoptosis following radiation exposure (percent change 0% vs. 85%; P = 0.002). A genome-wide microarray was used to compare gene expression 24 hours following radiation between HPV+ and HPV- cell lines. Multiple genes in TP53 pathway were upregulated in HPV+ cells (Z score 4.90), including a 4.6-fold increase in TP53 (P < 0.0001). Using immortalized human tonsillar epithelial (HTE) cells, increased radiation sensitivity was seen in cell expressing HPV-16 E6 despite the effect of E6 to degrade p53. This suggested that low levels of normally functioning p53 in HPV+ HNC cells could be activated by radiation, leading to cell death. Consistent with this, more complete knockdown of TP53 by siRNA resulted in radiation resistance. These results provide clear evidence, and a supporting mechanism, for increased radiation sensitivity in HPV+ HNC relative to HPV- HNC. This issue is under active investigation in a series of clinical trials attempting to de-escalate radiation (and chemotherapy) in selected patients with HPV+ HNC in light of their favorable overall survival outcome.

Indexed as

AnimalsApoptosisCell Line, TumorFemaleHead and Neck NeoplasmsHumansImmunoblottingMicePapillomavirus InfectionsRadiation ToleranceReverse Transcriptase Polymerase Chain ReactionTranscriptomeTumor Suppressor Protein p53Xenograft Model Antitumor AssaysTumor Suppressor Protein p53

Identifiers

PMID23749640
PMCPMC3732540
OpenAlexW2114119309

What OpenQuestion holds

Textmetadata
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.