Journal Article

DKFZ-2025-01873

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Circulating tumor human papillomavirus DNA whole genome sequencing enables human papillomavirus-associated oropharynx cancer early detection.

Das, D. ; Hirayama, S. ; Aye, L. ; Bryan, M. E. ; Naegele, S. ; Zhao, B. ; Efthymiou, V. ; Mendel, J. ; Fisch, A. S. ; Guan, Z. ; Kröller, L.DKFZ* ; Michels, B. E.DKFZ* ; Waterboer, T.DKFZ* ; Richmon, J. D. ; Adalsteinsson, V. ; Lawrence, M. S. ; Crowson, M. G. ; Iafrate, A. J. ; Faden, D. L.

2026
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:DOI:10.1093/jnci/djaf249  doi:DOI:10.1093/jnci/djaf249

Abstract: Early detection of HPV-associated oropharyngeal cancer (HPV+OPSCC), the most common HPV cancer in the United States, could reduce disease-related morbidity and mortality, yet currently, there are no early detection tests. Circulating tumor HPV DNA (ctHPVDNA) is a sensitive and specific biomarker for HPV+OPSCC at diagnosis. It is unknown if ctHPVDNA is detectable prior to diagnosis, and thus it's potential as an early detection test.Plasma samples from the MassGeneralBrigham biobank collected 1.3-10.8 years prior to diagnosis from HPV+OPSCC patients (n = 28) and age- and sex-matched controls (n = 28) were blinded and run on a newly developed and validated multi-feature HPV whole genome sequencing liquid biopsy assay and a validated HPV antibody assay.ctHPVDNA results were positive in 22/28 pre-diagnostic samples from HPV+OPSCC cases (sensitivity 79%) with a maximum lead time of 7.8 years. ctHPVDNA results were negative in all controls (0/28 controls, 100% specificity). Diagnostic accuracy was highest within four years of cancer diagnosis and was higher than HPV Ab detection within the same time frame (p-value 0.004). Application of a machine learning model trained and tested on an independent cohort of 306 cases and controls increased the sensitivity of detection to 27/28 cases (overall sensitivity 96%) and the maximum lead time to 10.3 years.Circulating tumor HPV DNA can be detected in the blood years prior to diagnosis with HPV+OPSCC, with high specificity, in a case-control cohort of 56 participants. ctHPVDNA detection alone, or in combination with previously identified serological biomarkers may be a feasible approach to early detection of HPV+OPSCC.

Note: ISSN 0027-8874 / 2026 Jan 1;118(1):58-67

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Contributing Institute(s):

1. Infektionen und Krebs-Epidemiologie (D320)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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