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A novel blood test, HPV-DeepSeek, shows it can reveal head and neck cancers linked to HPV up to 10 years before symptoms arise. The findings hint at a future where these cancers could be treated far earlier and less aggressively. Credit: Shutterstock
Mass General Brigham’s HPV-DeepSeek test enables much earlier cancer detection through a blood sample, creating a new opportunity for screening HPV-related head and neck cancers.
Study overview and significance
A federally funded study published in the Journal of the National Cancer Institute reports that HPV-DeepSeek, a liquid biopsy developed by researchers at Mass General Brigham, can identify HPV-associated head and neck cancers many years before clinical diagnosis. Human papillomavirus (HPV) now accounts for roughly 70% of oropharyngeal and other head and neck cancers in the United States, and incidence has been rising. Unlike cervical HPV cancers—where screening programs and Pap/HPV tests have reduced advanced disease—there is currently no routine blood-based screening to detect HPV-driven head and neck cancers early.
The absence of early detection means most patients present when tumors have grown substantially and often spread to lymph nodes, requiring aggressive surgery, radiation, and chemotherapy that can result in long-term complications. A reliable pre-symptomatic screen could shift treatment toward earlier, less invasive interventions and improve survival and quality of life.
What the researchers found
Investigators analyzed 56 archived blood samples from the Mass General Brigham Biobank: 28 from people who later developed HPV-associated head and neck cancer and 28 matched controls who remained cancer-free. Using whole-genome sequencing and targeted analysis to detect tiny fragments of HPV DNA circulating in plasma—often referred to as circulating tumor DNA (ctDNA)—HPV-DeepSeek initially detected viral tumor DNA in 22 of the 28 eventual cancer cases while all controls tested negative, indicating high specificity.
Detection rates improved further after applying machine-learning classifiers developed by the research team: the refined model correctly identified 27 of 28 cancer cases, including positive signals in samples collected as many as 10 years before diagnosis. The earliest positive sample without model enhancement dated to 7.8 years prior to clinical diagnosis. Earlier work by the same group reported near-ideal performance (about 99% sensitivity and specificity) when the test was used at a patient’s initial clinic visit, outperforming many existing diagnostic approaches.
How HPV-DeepSeek works
Whole-genome sequencing and ctDNA
HPV-DeepSeek uses deep whole-genome sequencing to search plasma for short DNA fragments that originate from tumor cells infected with high-risk HPV strains. Tumors shed DNA into the bloodstream; detecting these fragments can reveal a tumor’s presence before it produces symptoms. Because HPV DNA sequences are distinct from the human genome, assays that target viral fragments can have high analytical specificity.
Machine learning and signal enhancement
Machine-learning models help distinguish true low-level viral signals from background noise and technical artifacts. By training on known positive and negative samples, the algorithm increases sensitivity for very early, low-burden disease while maintaining specificity—critical for any population screening program to avoid false positives and unnecessary invasive follow-up.
Implications, validation, and challenges
If validated at scale, HPV-DeepSeek could form the basis of screening programs for high-risk populations—such as certain age groups, people with known HPV exposure, or those with risk behaviors—enabling clinicians to detect tumors when they are microscopic and more treatable. Earlier diagnosis could reduce the need for disfiguring surgery or high-dose radiation and lower long-term morbidity associated with current treatments.
However, several hurdles remain. Large, blinded validation studies are necessary to confirm performance across diverse populations and sample collection conditions. The research team is running a second NIH-funded blinded study using hundreds of samples from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to validate findings and estimate real-world positive predictive value and lead time. Cost, access to high-depth sequencing, and clinical pathways for follow-up of positive screens will also factor into whether the test can be deployed widely.
Expert Insight
"A sensitive, specific blood test for HPV-driven head and neck cancer could change the clinical landscape," says Dr. Maya Singh, a molecular epidemiologist not involved in the study. "The most important next steps are large-scale validation and defined protocols for follow-up diagnostics so that a positive blood test leads to timely, minimally invasive confirmation and treatment. If those elements fall into place, this approach could substantially reduce morbidity from these cancers."
Conclusion
HPV-DeepSeek represents a promising advance in liquid biopsy technology and cancer screening. By combining whole-genome sequencing with machine learning to detect circulating HPV DNA, the test has shown the ability to flag HPV-associated head and neck cancers years before symptoms appear. Ongoing NIH-funded validation using PLCO samples will be crucial to determine whether HPV-DeepSeek can move from a research tool into routine clinical screening—potentially enabling earlier, less aggressive treatment and better outcomes for patients.
Source: scitechdaily
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