Mass General Brigham researchers have developed a groundbreaking liquid biopsy blood test that achieves unprecedented accuracy in detecting HPV-associated head and neck cancers, potentially transforming early cancer screening and patient care. The test, called HPV-DeepSeek, demonstrated 99% sensitivity and 99% specificity for diagnosing cancer at the time of first clinical presentation, including for the very earliest stages of disease.
Superior Performance Over Current Methods
The research, published in Clinical Cancer Research, shows that HPV-DeepSeek significantly outperforms current standard-of-care methods and other commercially available liquid biopsy assays. The study tested the assay in 152 patients with HPV-associated head and neck cancer and 152 healthy controls, conducting head-to-head comparisons with existing liquid and tissue biopsy approaches.
"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 Daniel Faden, MD, lead author and principal investigator in the Mike Toth Head and Neck Cancer Research Center at Mass Eye and Ear. "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."
Advanced Whole-Genome Sequencing Technology
HPV-DeepSeek detects fragments of the viral genome that have broken off from tumors and entered the bloodstream, along with nine other features in the blood. The key innovation lies in its use of whole-genome sequencing of the entire HPV genome, unlike current liquid biopsy approaches that only target one to two pieces of the viral genome.
This comprehensive approach allows physicians to look for "many hundreds or thousands of needles in haystacks as opposed to just a few, drastically increasing sensitivity," according to Faden. The enhanced sensitivity translates to significantly more accurate results for patients.
Early Detection Breakthrough
Perhaps most significantly, researchers demonstrated the test's potential for pre-symptomatic screening. In a preprint study presented at the 2024 AACR Special Conference in Cancer Research, the team tested HPV-DeepSeek in 28 people who years later developed HPV-associated oropharynx cancer and 28 healthy controls. The assay detected cancer in 79% of individuals who later developed the disease, while all controls tested negative. The earliest positive result occurred nearly eight years before clinical diagnosis.
"The natural history of these cancers is that they grow over a period of about 15 years, and as they grow they release DNA from the HPV genome into the blood," Faden explained. "If we can detect these cancers years earlier, at their earliest stages, it could drastically change how we treat patients; for example, being able to use less treatment leading to fewer side effects."
Addressing Critical Unmet Need
The development addresses a significant gap in cancer screening. HPV causes approximately 70% of oropharyngeal cancers in the United States, which are increasing in incidence faster than all other head and neck cancers. Unlike cervical cancer, which is also caused by HPV, there are currently no early detection tests for HPV-associated head and neck cancers. This means patients typically present to doctors only after experiencing symptoms, requiring treatments that may carry significant side effects.
Complementary Research in Non-HPV Cancers
In a separate study published in the same issue of Clinical Cancer Research, Faden's team tested a different assay called MAESTRO in patients with head and neck cancer not caused by HPV. Developed at the Broad Institute of MIT and Harvard, MAESTRO uses a specialized approach to detect genome-wide tumor DNA with minimal sequencing to look for evidence of cancer remaining after surgery.
The test accurately detected residual cancer within days of surgery in highly aggressive head and neck cancers, with patients showing residual disease having significantly worse survival and recurrence outcomes. "MAESTRO not only detected residual cancer in more patients who experienced future recurrence or death but also was highly predictive for it," said Viktor Adalsteinsson, PhD, who directs the Gerstner Center for Cancer Diagnostics at the Broad Institute.
Future Clinical Applications
The research team is now conducting additional studies to address implementation questions, including optimal follow-up regimens for patients who screen positive and the role of HPV-DeepSeek in detecting microscopic residual disease after surgery. These studies aim to determine whether additional treatments like radiation therapy are needed based on liquid biopsy results.
The breakthrough represents a significant step toward personalized cancer care, with whole-genome sequencing liquid biopsy approaches offering the potential to revolutionize both early detection and post-treatment monitoring for HPV-associated cancers.
