Evidence map›Paper›PMID 34857594›Full record

Observational studyClinical cancer research : an official journal of the American Association for Cancer Research2022

Cell-Free HPV DNA Provides an Accurate and Rapid Diagnosis of HPV-Associated Head and Neck Cancer.

Giulia Siravegna, Connor J O'Boyle, Shohreh Varmeh, Natalia Queenan, Alexa Michel, Jarrod Stein, Julia Thierauf, Peter M Sadow, William C Faquin, Simon K Perry and 17 more

Open access · bronzeAbstract readObservational Study
In one paragraph

Observational study in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 3 pooled it
12.9field-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.

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

59 citing papers in PubMed, 3 syntheses or guidelines pooled it, 108 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Article
  5. Article
  6. Article
  7. Explore the role of ctHPVDNA kinetics during diagnosis and follow-up of HPV OPSCC.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 · 2026
    Article
  8. Article
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  12. Review
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  17. Circulating Tumor Tissue-Modified-Viral HPV DNA and Correlations With Disease Burden in Oropharyngeal Cancer.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2025
    Article
  18. Circulating Tumour DNA as a Complementary Tool for Treatment Evaluation in HPV-Associated Head and Neck Squamous Cell Carcinoma: An Observational Cohort Study.Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery · 2025
    Observational
  19. Review
  20. Observational
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 6 institutions in 1 country.

Giulia Siravegna *Harvard Medical School, Boston, Massachusetts.
Connor J O'Boyle *Department of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, Boston, Massachusetts.
Shohreh VarmehDepartment of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, Boston, Massachusetts.
Natalia QueenanDepartment of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, Boston, Massachusetts.
Alexa MichelMassachusetts General Hospital Cancer Center, Boston, Massachusetts.ORCID 0000-0002-7975-9612
Jarrod SteinDepartment of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, Boston, Massachusetts.
Julia ThieraufDepartment of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
Peter M SadowHarvard Medical School, Boston, Massachusetts.ORCID 0000-0003-1036-6367
William C FaquinHarvard Medical School, Boston, Massachusetts.ORCID 0000-0002-9043-7171
Simon K PerryDepartment of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
Adam Z BardDepartment of Pathology, Massachusetts General Hospital, Boston, Massachusetts.ORCID 0000-0003-1091-7843
Wei WangDepartments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts.
Daniel G DeschlerHarvard Medical School, Boston, Massachusetts.
Kevin S EmerickHarvard Medical School, Boston, Massachusetts.
Mark A VarvaresHarvard Medical School, Boston, Massachusetts.
Jong C ParkHarvard Medical School, Boston, Massachusetts.ORCID 0000-0002-1052-0734
John R ClarkHarvard Medical School, Boston, Massachusetts.
Annie W ChanHarvard Medical School, Boston, Massachusetts.
Vanessa Carlota Andreu ArasaDepartment or Radiology, Boston Medical Center, Boston, Massachusetts.ORCID 0000-0003-3883-8725
Osamu SakaiDepartment or Radiology, Boston Medical Center, Boston, Massachusetts.
Jochen LennerzHarvard Medical School, Boston, Massachusetts.ORCID 0000-0003-2434-4978
Ryan B CorcoranHarvard Medical School, Boston, Massachusetts.
Lori J WirthHarvard Medical School, Boston, Massachusetts.
Derrick T LinHarvard Medical School, Boston, Massachusetts.
A John IafrateHarvard Medical School, Boston, Massachusetts.
Jeremy D Richmon *Harvard Medical School, Boston, Massachusetts.
Daniel L Faden *Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-5284-7762
Massachusetts Eye and Ear Infirmary · USHarvard University · USMassachusetts General Hospital · USBoston Medical Center · USBrigham and Women's Hospital · USBroad Institute · US

Funding

Tissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI EL-BARDEESY, NABEEL, SELLERS, WILLIAM R · 2007 to 2023
$33.2M
Project 2U54CA224068 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CORCORAN, RYAN BRUCE, FLAHERTY, KEITH T · 2017 to 2021
$6.3M
Therapeutic resistance and tumor heterogeneity in BRAF mutant colorectal cancerR01CA208437 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CORCORAN, RYAN BRUCE · 2016 to 2020
$2.0M
NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA208437NCI NIH HHS U54 CA224068
6 · The paper itself

Abstract

purposeHPV-associated head and neck squamous cell carcinoma (HPV+HNSCC) is the most common HPV-associated malignancy in the United States and continues to increase in incidence. Current diagnostic approaches for HPV+HNSCC rely on tissue biopsy followed by histomorphologic assessment and detection of HPV indirectly by p16 IHC. Such approaches are invasive and have variable sensitivity. EXPERIMENTAL

designWe conducted a prospective observational study in 140 subjects (70 cases and 70 controls) to test the hypothesis that a noninvasive diagnostic approach for HPV+HNSCC would have improved diagnostic accuracy, lower cost, and shorter diagnostic interval compared with standard approaches. Blood was collected, processed for circulating tumor HPV DNA (ctHPVDNA), and analyzed with custom ddPCR assays for HPV genotypes 16, 18, 33, 35, and 45. Diagnostic performance, cost, and diagnostic interval were calculated for standard clinical workup and compared with a noninvasive approach using ctHPVDNA combined with cross-sectional imaging and physical examination findings.

resultsSensitivity and specificity of ctHPVDNA for detecting HPV+HNSCC were 98.4% and 98.6%, respectively. Sensitivity and specificity of a composite noninvasive diagnostic using ctHPVDNA and imaging/physical examination were 95.1% and 98.6%, respectively. Diagnostic accuracy of this noninvasive approach was significantly higher than standard of care (Youden index 0.937 vs. 0.707, P = 0.0006). Costs of noninvasive diagnostic were 36% to 38% less than standard clinical workup and the median diagnostic interval was 26 days less.

conclusionsA noninvasive diagnostic approach for HPV+HNSCC demonstrated improved accuracy, reduced cost, and a shorter time to diagnosis compared with standard clinical workup and could be a viable alternative in the future.

Indexed as

Cell-Free Nucleic AcidsHead and Neck NeoplasmsPapillomavirus InfectionsDNA, ViralHumansPapillomaviridaeCell-Free Nucleic AcidsDNA, Viral

Identifiers

PMID34857594
PMCPMC8866203
OpenAlexW3215359719

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.