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

作者：Dipon Das, Shun Hirayama, Ling Aye, Michael Bryan, Saskia Naegele, Brian Y. Zhao, Vasileios Efthymiou, Julia Mendel, Adam S. Fisch, Zoe Guan, Lea Kröller, Birgitta E. Michels, Tim Waterboer, Jeremy D. Richmon, Viktor A. Adalsteinsson, Michael S. Lawrence, Matthew G. Crowson, A. John Iafrate, Daniel L. Faden · 发表于：JNCI Journal of the National Cancer Institute · 年份：2025 · DOI：10.1093/jnci/djaf249 · 被引用次数：11 · 研究领域：Cancer Genomics and Diagnostics、Head and Neck Cancer Studies、Esophageal Cancer Research and Treatment

BACKGROUND: Early 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. METHODS: Plasma 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. RESULTS: HPV 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 ...