According to the American Cancer Society (ACS), human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) is the most common type of HPV-related malignancy in the United States. In 2025, ACS estimates there will be 59,660 diagnoses of mouth and throat cancers, and about 70% will be caused by HPV.
Because some common head and neck cancer symptoms, such as a sore throat or sinus infection, may be mistaken for a less serious health condition, these cancers often present clinically at advanced stages, leading to poorer outcomes. The results of a recent study investigating a novel, multifeatured, HPV whole-genome sequencing early detection liquid biopsy test called HPV-DeepSeek showed the test was able to detect HPV-related head and neck cancers up to a decade before symptoms developed.
The study’s results highlight the potential of circulating tumor DNA (ctDNA) early detection approaches for cancers that currently lack screening tests, according to the study authors. The study by Das et al was published in JNCI: Journal of the National Cancer Institute.
Study Methodology and Results
The researchers analyzed plasma samples from 28 patients stored in the Mass General Brigham biobank and collected 1.3 to 10.8 years prior to the diagnosis of HPV-related head and neck cancers and compared them with 28 age- and sex-matched controls. The analysis was performed on a newly developed and validated multifeatured HPV whole-genome sequencing liquid biopsy assay and a validated HPV antibody (Ab) assay.
The researchers found that the circulating tumor HPV DNA results were positive in 22 of the 28 prediagnostic samples from the patients with HPV-associated oropharyngeal cancer (sensitivity of 79%) with a maximum lead time of 7.8 years. The circulating tumor HPV DNA results were negative in all 28 controls (specificity of 100%).
Diagnostic accuracy was highest within 4 years of a cancer diagnosis and was higher than HPV Ab detection within the same time frame (P = .004). Application of a machine learning model trained and tested on an independent cohort of 306 patients and controls increased the sensitivity of detection to 27 of the 28 cases (overall sensitivity of 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. Circulating tumor HPV DNA detection alone or in combination with previously identified serological biomarkers may be a feasible approach to early detection of HPV+ OPSCC,” concluded the study authors.
Daniel L. Faden, MD, FACS, of the Department of Otolaryngology–Head and Neck Surgery at Harvard Medical School and the Mike Toth Head and Neck Cancer Research Center, Massachusetts Eye and Ear in Boston, is the corresponding author of this study.
Disclosure: Funding for this study was provided by the National Institutes of Health. The study authors’ financial conflict of interest disclosures may be found at https://academic.oup.com/jnci#google_vignette.
