A new liquid biopsy blood analysis could help detect cases of head and neck cancers associated with human papilloma (HPV) with significantly greater accuracy than the methods currently used, even before patients develop symptoms, according to a new Brigham general research.
Mass Eye and Ear researchers, a member of the Mass Brigham General Health System, found that the blood-based diagnostic test they developed called HPV-Depseek reached a sensitivity of 99% and a 99% specificity to diagnose cancer at the time of the first clinical presentation, even for the oldest stages of the disease. This greater precision significantly exceeds current standard care methods, including other liquid biopsy tests commercially available. The study is published in Clinical Cancer ResearchAn American Cancer Research Association Magazine.
HPV causes about 70% of oropharyngeal cancers in the United States, which are increasing in incidence faster than all other heads and neck cancers, but unlike cervical cancer, which is also caused by HPV, there is no early detection tests. This means that patients generally present doctors once they experience symptoms, which requires treatments that may have significant side effects, according to the main author of the study, Daniel Faden, MD, principal researcher at the Mike Toth Head and Teck cancer research center and the surgical oncologist and in Mass Eye and Ear.
“The objective of developing HPV-Depseek 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 show that we can use this approach not only to diagnose patients with greater precision compared to what is currently available, but also provide the potential to detect HPV cancers in the blood before patients develop symptoms, which allows us to catch and treat their cancers in the early stages.”
The VPV-Depseek detects fragments of the viral genome that have broken from the tumor and have entered the bloodstream, along with nine other characteristics in the blood. Unlike the current liquid biopsy approaches, which only go to one or two pieces of the viral genome, HPV-Depseek uses the full genome sequencing of the entire HPV genome. In the new study, the researchers evaluated the SPV-Depseek in 152 patients with head and neck cancer associated with HPV and 152 healthy controls. Then they made a face -to -face comparison with methods that include current liquid and tissue biopsy approaches. They found that this new approach led to significantly improved sensitivity and precision.
Researchers are now leading additional studies around HPV defense, including their role in cancer detection years before tumors develop. In a study that is currently in predimpression, they tested the trial in 28 people who years later developed oropharynx cancer associated with HPV and 28 healthy controls. They discovered that they could detect cancer in 79% of people who later developed cancer, while all controls had negative evidence. The most early positive result was almost eighty before diagnosis, which shows for the first time that highly precise blood detection for HPV cancer is feasible. This work was also presented at Symposium 2024, AACR Special Conference on Cancer Research: liquid biopsy: from discovery to clinical implementation.
“The natural history of these cancers is that they grow for a period of approximately 15 years, and as they grow they release the DNA of the HPV genome to the blood. If we can detect these types of cancer years before, in their early stages, it could drastically change the way we treat patients; for example, be able to use less treatment with less secondary effects,” said Faden. “While our results suggest great potential for clinical benefit, there are unanswered questions that we should address to understand how we could better use these approaches and what would be the monitoring regimes for patients who show positive.”
The team is now executing studies to address these questions on the head and neck associated with HPV and other HPV cancers. In addition to the detection, the equipment is also executing clinical trials to study the effectiveness of the detection of remaining microscopic diseases after surgery, which could inform if additional treatments such as radiotherapy are needed.
The use of liquid biopsy for the early detection of cancer and the customization of treatment after surgery is an area of growth in other forms of head and neck cancer. In a separate study published in the same number of Clinical Cancer ResearchFaden and his team tested a different novel essay called Master in patients with head and neck cancer not caused by HPV to seek evidence of remaining cancer after surgery. Developed at the Broad Institute of Mit and Harvard, this approach improves sensitivity through the use of a specialized approach to detect the tumor DNA of the entire genome with a minimal sequencing. They discovered that the test could accurately detect residual cancer within a few days of surgery in a highly aggressive form of head and neck cancer and that patients with residual disease detected by the trial had significantly worse survival and recurrence results.
“People have always wondered if the most sensitive liquid biopsy tests will begin to detect residual cancer that will not lead to recurrence,” said Viktor Adalsteinsson, PHD, who directs the Gerstner center for the diagnosis of cancer in the Broad Institute, and whose team developed the teacher. “In this study, the teacher not only detected residual cancer in more patients who experienced recurrence or future death, but was also highly predictive for it.”
“The liquid biopsy approaches to complete genome sequencing, such as the HPV-DESEEK and Metro used in these studies, are enormously powerful, which allows doctors to look for many hundreds or thousands of needles in the pinch instead of a few sensitivity drastically increasing,” said Faden. “For patients, this means significantly more precise results and being one step closer to truly personalized care.”