Evidence map›Paper›PMID 40925715›Full record

ArticleJournal of the National Cancer Institute2026

Circulating tumor human papillomavirus DNA whole genome sequencing enables human papillomavirus-associated oropharynx cancer early detection.

Dipon Das, Shun Hirayama, Ling Aye, Michael E Bryan, Saskia Naegele, Brian Zhao, Vasileios Efthymiou, Julia Mendel, Adam S Fisch, Zoe Guan and 9 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the National Cancer Institute, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07718620 (Validation of a New Method for Monitoring HPV Infection in Patients With Head and Neck Cancers), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–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.

NCT07718620 narecruitingnot on this map

Validation of a New Method for Monitoring HPV Infection in Patients With Head and Neck Cancers

TypeinterventionalSponsorMasaryk Memorial Cancer InstituteRan2026 to 2027Enrolled35ConditionsOropharyngeal Carcinoma (OPC)ArmsHPV p16, HPV testing - positive results, HPV testing - negative results
3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Dipon DasDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, United States.
Shun HirayamaDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, United States.ORCID 0009-0000-6298-5392
Ling AyeDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, United States.
Michael E BryanDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, United States.ORCID 0000-0001-8306-009X
Saskia NaegeleDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, United States.ORCID 0000-0002-0935-7861
Brian ZhaoDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, United States.
Vasileios EfthymiouDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, United States.ORCID 0000-0001-6139-9535
Julia MendelDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, United States.
Adam S FischMassachusetts Eye and Ear, Boston, MA, United States.ORCID 0000-0002-4742-8165
Zoe GuanMassachusetts General Hospital Biostatistics, Boston, MA, United States.ORCID 0000-0002-1015-4666
Lea KröllerDivision of Infections and Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.ORCID 0009-0008-9365-0796
Birgitta E MichelsDivision of Infections and Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.ORCID 0000-0001-9948-4567
Tim WaterboerDivision of Infections and Cancer Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.ORCID 0000-0002-0616-6963
Jeremy D RichmonDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, United States.ORCID 0000-0002-6588-6549
Viktor AdalsteinssonBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, United States.ORCID 0000-0003-4555-2485
Michael S LawrenceDepartment of Pathology, Massachusetts General Hospital, Boston, MA, United States.
Matthew G CrowsonDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, United States.ORCID 0000-0001-9950-0985
A John IafrateDepartment of Pathology, Massachusetts General Hospital, Boston, MA, United States.
Daniel L FadenDepartment of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, United States.ORCID 0000-0001-5284-7762

Funding

The Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0M
Dissecting temporal and spatial dynamics of immunotherapy resistanceK23DE029811 · NIDCR · MASSACHUSETTS EYE AND EAR INFIRMARY · PI FADEN, DANIEL · 2021 to 2025
$869k
Circulating HPV DNA as a Prediagnostic Marker of Oropharyngeal CancerR21CA267152 · NCI · UNIVERSITY OF KENTUCKY · PI FADEN, DANIEL, KUHS, KRYSTLE A. · 2022 to 2023
$431k
Cell free HPV DNA detection in the diagnostic and surgical settingsR03DE030550 · NIDCR · MASSACHUSETTS EYE AND EAR INFIRMARY · PI FADEN, DANIEL · 2022 to 2023
$336k
NCATS NIH HHS UL1 TR002541NCI NIH HHS R21 CA267152NIDCR NIH HHS K23 DE029811NIDCR NIH HHS R03 DE030550NIDCR NIH HHS R03DE030550NIDCR NIH HHS R21 CA267152NIH
6 · The paper itself

Abstract

backgroundEarly detection of HPV-associated oropharyngeal squamous cell carcinoma, the most common HPV cancer in the United States, could reduce disease-related morbidity and mortality, yet currently, there are no early detection tests. HPV circulating tumor DNA (ctDNA) is a sensitive and specific biomarker for HPV-associated oropharyngeal squamous cell carcinoma at diagnosis. It is unknown if ctDNA HPV is detectable prior to diagnosis, and thus its potential as an early detection test is also unknown.

methodsPlasma samples from the Mass General Brigham Biobank collected 1.3-10.8 years prior to diagnosis from HPV-associated oropharyngeal squamous cell carcinoma patients (n = 28) and age- and sex-matched controls (n = 28) were blinded and run on a newly developed and validated multifeature HPV whole genome sequencing liquid biopsy assay and a validated HPV antibody assay.

resultsHPV ctDNA results were positive in 22 of 28 prediagnostic samples from HPV-associated oropharyngeal squamous cell carcinoma cases (sensitivity 79%) with a maximum lead time of 7.8 years. HPV ctDNA results were negative in all controls (0 of 28, 100% specificity). Diagnostic accuracy was highest within 4 years of cancer diagnosis and was higher than HPV Ab detection within the same timeframe (P = .004). Application of a machine-learning model trained and tested on an independent cohort of 306 cases and controls increased the sensitivity of detection to 27 of 28 cases (overall sensitivity 96%) and the maximum lead time to 10.3 years.

conclusionsHPV ctDNA can be detected in the blood years prior to diagnosis with HPV-associated oropharyngeal squamous cell carcinoma, with high specificity, in a case-control cohort of 56 participants. HPV ctDNA detection alone, or in combination with previously identified serological biomarkers, may be a feasible approach to early detection of HPV-associated oropharyngeal squamous cell carcinoma.

Indexed as

Carcinoma, Squamous CellCirculating Tumor DNADNA, ViralEarly Detection of CancerOropharyngeal NeoplasmsPapillomaviridaePapillomavirus InfectionsAdultAgedBiomarkers, TumorCase-Control StudiesFemaleHuman Papillomavirus VirusesHumansMaleMiddle AgedBiomarkers, TumorCirculating Tumor DNADNA, Viral

Identifiers

PMID40925715
PMCPMC12794221

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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.