Health Matters
A new liquid biopsy blood test could help detect cases of human papillomavirus (HPV)-associated head and neck cancers with significantly higher accuracy than currently used methods, including before patients develop symptoms, according to new Mass General Brigham research.
The researchers at Mass Eye and Ear, a member of the Mass General Brigham healthcare system, found that the blood-based diagnostic test they developed called HPV-DeepSeek achieved 99% sensitivity and 99% specificity for diagnosing cancer at the time of first clinical presentation, including for the very earliest stages of disease. This higher accuracy significantly outperforms current standard-of-care methods, including other commercially available liquid biopsy assays.
HPV causes about 70% of oropharyngeal cancers in the United States, which are increasing in incidence faster than all other head and neck cancers, yet unlike cervical cancer, which is also caused by HPV, there are no early detection tests. This means patients typically present to doctors once they are experiencing symptoms, requiring treatments that may carry significant side effects, according to the study’s lead author Daniel Faden, MD, a principal investigator in the Mike Toth Head and Neck Cancer Research Center and Surgical Oncologist and at Mass Eye and Ear.
“The goal of developing HPV-DeepSeek was to create a minimally invasive approach to detect HPV cancers that is significantly more sensitive than what is currently available for patients,” said Faden. “Our findings demonstrate that we can use this approach to not only diagnose patients more accurately compared to what is currently available, but also provide the potential to screen for HPV cancers in the blood before patients ever develop symptoms, enabling us to catch and treat their cancers at the earliest stages.”
HPV-DeepSeek detects fragments of the viral genome that have broken off from the tumor and entered the bloodstream, along with nine other features in the blood. Unlike current liquid biopsy approaches, which only target one to two pieces of the viral genome, HPV-DeepSeek uses whole-genome sequencing of the entire HPV genome. In the new study, researchers tested HPV-DeepSeek in 152 patients with HPV-associated head and neck cancer and 152 healthy controls. They then did a head-to-head comparison with methods including current liquid and tissue biopsy approaches. They found this novel approach led to a significantly improved sensitivity and accuracy.
The researchers are now leading additional studies around HPV-DeepSeek, including its role in screening for cancers years before the tumors develop. In a study that currently is in preprint, they tested the assay in 28 people who years later went on to develop HPV-associated oropharynx cancer and 28 healthy controls. They found they could detect the cancer in 79% of individuals who later developed cancer while all the controls had negative testing. The earliest positive result was nearly eightyears before diagnosis, demonstrating for the first time that highly accurate blood-based screening for HPV cancer is feasible.
