Evidence map›Paper›PMID 35139236›Full record

Observational studyCancer2022

Cell-free human papillomavirus DNA kinetics after surgery for human papillomavirus-associated oropharyngeal cancer.

Connor J O'Boyle, Giulia Siravegna, Shohreh Varmeh, Natalia Queenan, Alexa Michel, Kim Chang Sing Pang, Jarrod Stein, Julia C Thierauf, Peter M Sadow, William C Faquin and 14 more

Registry-linked trialOpen access · bronzeAbstract readObservational Study
In one paragraph

Observational study in Cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05649865 (Analysis of HPV DNA in Plasma in Patients With HPV-positive Oropharyngeal Squamous Cell Carcinoma - a Prospective Study of HPV DNA Levels for Treatment Response and Surveillance), which is not on this map. Cited by 49 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 5 pooled it
14.9field-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.

NCT05649865 recruitingnot on this mapstarted 2023, after this paper: background citation

Analysis of HPV DNA in Plasma in Patients With HPV-positive Oropharyngeal Squamous Cell Carcinoma - a Prospective Study of HPV DNA Levels for Treatment Response and Surveillance

Typeobservational_patient_registrySponsorRegion SkaneRan2023 to 2028Enrolled150ConditionsOropharynx Squamous Cell CarcinomaArmsBlood sample
3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 5 syntheses or guidelines pooled it, 76 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Article
  8. Article
  9. Review
  10. Article
  11. Redefining oropharyngeal cancer in the HPV era: integrating precision medicine and immunotherapeutic frontiers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  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. Article
  19. Review
  20. Observational
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 5 institutions in 2 countries.

Connor J O'BoyleDepartment of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, Boston, Massachusetts.
Giulia SiravegnaHarvard Medical School, 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.
Kim Chang Sing PangDepartment of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, Boston, Massachusetts.
Jarrod SteinDepartment of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, Boston, Massachusetts.
Julia C ThieraufDepartment of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
Peter M SadowDepartment of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, Boston, Massachusetts.
William C FaquinDepartment of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, Boston, Massachusetts.
Wei WangDepartment of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Daniel G DeschlerDepartment of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, Boston, Massachusetts.
Kevin S EmerickDepartment of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, Boston, Massachusetts.
Mark A VarvaresDepartment of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, 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.
Paul M BusseHarvard Medical School, Boston, Massachusetts.
Ryan B CorcoranHarvard Medical School, Boston, Massachusetts.
Lori J WirthHarvard Medical School, Boston, Massachusetts.ORCID 0000-0002-2629-2289
Derrick T LinDepartment of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, Boston, Massachusetts.
A John IafrateHarvard Medical School, Boston, Massachusetts.
Jeremy D RichmonDepartment of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, Boston, Massachusetts.
Daniel L FadenDepartment of Otolaryngology-Head and Neck Surgery Massachusetts Eye and Ear, Boston, Massachusetts.ORCID 0000-0001-5284-7762
Massachusetts Eye and Ear Infirmary · USHarvard University · USMassachusetts General Hospital · USBrigham and Women's Hospital · USBroad Institute · US

Funding

Strategies to Overcome Immune Resistance in Head and Neck CancersP01CA240239 · NCI · YALE UNIVERSITY · PI MEMPEL, THORSTEN ROMAN · 2019 to 2023
$8.4M
Cell free HPV DNA detection in the diagnostic and surgical settingsR03DE030550 · NIDCR · MASSACHUSETTS EYE AND EAR INFIRMARY · PI FADEN, DANIEL · 2022 to 2023
$336k
NCI NIH HHS P01 CA240239NIDCR NIH HHS R03 DE030550
6 · The paper itself

Abstract

backgroundNew ultrasensitive methods for detecting residual disease after surgery are needed in human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC).

methodsTo determine whether the clearance kinetics of circulating tumor human papillomavirus DNA (ctHPVDNA) is associated with postoperative disease status, a prospective observational study was conducted in 33 patients with HPV+OPSCC undergoing surgery. Blood was collected before surgery, postoperative days 1 (POD 1), 7, and 30 and with follow-up. A subcohort of 12 patients underwent frequent blood collections in the first 24 hours after surgery to define early clearance kinetics. Plasma was run on custom droplet digital polymerase chain reaction (ddPCR) assays for HPV genotypes 16, 18, 33, 35, and 45.

resultsIn patients without pathologic risk factors for recurrence who were observed after surgery, ctHPVDNA rapidly decreased to <1 copy/mL by POD 1 (n = 8/8). In patients with risk factors for macroscopic residual disease, ctHPVDNA was markedly elevated on POD 1 (>350 copies/mL) and remained elevated until adjuvant treatment (n = 3/3). Patients with intermediate POD 1 ctHPVDNA levels (1.2-58.4 copies/mL) all possessed pathologic risk factors for microscopic residual disease (n = 9/9). POD 1 ctHPVDNA levels were higher in patients with known adverse pathologic risk factors such as extranodal extension >1 mm (P = .0481) and with increasing lymph nodes involved (P = .0453) and were further associated with adjuvant treatment received (P = .0076). One of 33 patients had a recurrence that was detected by ctHPVDNA 2 months earlier than clinical detection.

conclusionsPOD 1 ctHPVDNA levels are associated with the risk of residual disease in patients with HPV+OPSCC undergoing curative intent surgery and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future. LAY SUMMARY: Human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC) is increasing at epidemic proportions and is commonly treated with surgery. This report describes results from a study examining the clearance kinetics of circulating tumor HPV DNA (circulating tumor human papillomavirus DNA [ctHPVDNA]) following surgical treatment of HPV+OPSCC. We found that ctHPVDNA levels 1 day after surgery are associated with the risk of residual disease in patients with HPV+OPSCC and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future. These findings are the first to demonstrate the potential utility of ctHPVDNA in patients with HPV+OPSCC undergoing surgery.

Indexed as

AlphapapillomavirusCirculating Tumor DNAHead and Neck NeoplasmsOropharyngeal NeoplasmsPapillomavirus InfectionsHumansKineticsPapillomaviridaeSquamous Cell Carcinoma of Head and NeckCirculating Tumor DNAcell-free DNAcirculating tumor DNAhead and neck cancerhuman papillomavirus (HPV)oropharyngeal cancer

Identifiers

PMID35139236
PMCPMC10032347
OpenAlexW4210889410

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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.