New Blood Test Shows Superior Sensitivity in Detecting HPV-Associated Head and Neck Cancers
Posted on 23 May 2025
Human papillomavirus (HPV) is responsible for approximately 70% of oropharyngeal cancers in the United States, a cancer type that is rising in incidence more rapidly than all other head and neck cancers. Unlike cervical cancer, which is also caused by HPV and has early detection tests available, oropharyngeal cancer lacks such methods. This absence means that patients often present to healthcare providers only after experiencing symptoms, necessitating treatments that may carry significant side effects. Now, a new liquid biopsy blood test has been developed that could detect HPV-associated head and neck cancers with much higher accuracy than current methods, potentially identifying cases even before symptoms arise.
Researchers at Mass General Brigham (Somerville, MA, USA) have developed a blood-based diagnostic test, HPV-DeepSeek, which demonstrated 99% sensitivity and 99% specificity for detecting cancer at the time of first clinical presentation, including in the very early stages. This accuracy far exceeds that of current standard methods, including other commercially available liquid biopsy assays. HPV-DeepSeek works by identifying fragments of the viral genome that have detached from the tumor and entered the bloodstream, along with nine additional features found in the blood. Unlike current liquid biopsy methods that target only one or two fragments of the viral genome, HPV-DeepSeek uses whole-genome sequencing to examine the entire HPV genome. In a study published in Clinical Cancer Research, the researchers tested HPV-DeepSeek in 152 patients diagnosed with HPV-associated head and neck cancer and 152 healthy controls. The results showed a significant improvement in sensitivity and accuracy compared to existing methods.
The researchers are currently conducting further studies to explore the potential of HPV-DeepSeek, particularly its use in detecting cancers years before they develop. In a preprint study, they tested the assay in 28 individuals who later developed HPV-associated oropharyngeal cancer and 28 healthy controls. They found that they could detect the cancer in 79% of the individuals who developed cancer later, while all the controls tested negative. The earliest detection occurred nearly eight years before diagnosis, providing the first evidence that accurate blood-based screening for HPV-related cancer is possible. The team is now focusing on expanding these studies to examine HPV-associated head and neck cancers, as well as other HPV-related cancers. In addition to screening, the team is also conducting clinical trials to evaluate the effectiveness of the test in detecting microscopic residual disease after surgery, which could guide decisions regarding the need for additional treatments such as radiation therapy.
The use of liquid biopsy for early cancer detection and treatment personalization after surgery is an expanding area of research in head and neck cancers. In a separate study published in the same issue of Clinical Cancer Research, the team tested another novel assay, MAESTRO, for patients with head and neck cancers not caused by HPV, to detect remaining cancer after surgery. This test improves sensitivity by employing a specialized method to detect genome-wide tumor DNA with minimal sequencing. The results showed that the test could accurately detect residual cancer within a few days after surgery, particularly in highly aggressive forms of head and neck cancer. Patients with residual disease detected by the assay had significantly worse survival and recurrence rates.
“Whole-genome sequencing liquid biopsy approaches, like HPV-DeepSeek and MAESTRO used in these studies, are enormously powerful, allowing physicians to look for many hundreds or thousands of needles in haystacks as opposed to just a few, drastically increasing sensitivity,” said Daniel Faden, MD, FACS, lead author of the HPV-DeepSeek study. “For patients, this means significantly more accurate results and being one step closer to truly personalized care.”
