Circulating Tumor HPV DNA Can ID HPV+OPSCC Years Before Diagnosis
MONDAY, Sept. 22, 2025 -- Circulating tumor human papillomavirus DNA (ctHPVDNA) can be detected in the blood years prior to HPV-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC) diagnosis, according to a study published online Sept. 10 in the Journal of the National Cancer Institute.
Noting that ctHPVDNA is a sensitive and specific biomarker for HPV+OPSCC at diagnosis, Dipon Das, Ph.D., from Harvard Medical School in Boston, and colleagues examined whether ctHPVDNA is detectable prior to diagnosis. Plasma samples collected 1.3 to 10.8 years prior to diagnosis from 28 HPV+OPSCC patients and 28 age- and sex-matched controls were run on a newly developed and validated multifeature HPV whole-genome sequencing liquid biopsy assay and a validated HPV antibody assay.
The researchers found that 22 of 28 prediagnostic samples from HPV+OPSCC cases had positive ctHPVDNA results (sensitivity, 79 percent), with a maximum lead time of 7.8 years. In all controls, ctHPVDNA results were negative (specificity, 100 percent). Within four years of cancer diagnosis, diagnostic accuracy was highest. Diagnostic accuracy within four years of cancer diagnosis was also higher with ctHPVDNA compared with HPV antibody detection. Sensitivity of detection was increased to 27/28 cases (overall sensitivity, 96 percent), and the maximum lead time was increased to 10.3 years with application of a machine learning model trained and tested on an independent cohort of 306 cases and controls.
"Our study shows for the first time that we can accurately detect HPV-associated cancers in asymptomatic individuals many years before they are ever diagnosed with cancer," lead author Daniel L. Faden, M.D., also from Harvard Medical School, said in a statement.
Several authors disclosed ties to the biopharmaceutical industry.
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