10 Years Earlier: New Blood Test Identifies Head and Neck Cancer Early

Scientists have discovered that fragments of HPV virus DNA can be found in the blood up to 10 years before a throat cancer diagnosis. This discovery could lead to the development of a blood test capable of detecting cancer long before the first symptoms appear, offering a greater chance of early treatment and cure.

Oropharyngeal cancer associated with the human papillomavirus (HPV), also known as HPV-positive (HPV+OPSCC), is currently the most common type of HPV-related cancer in the United States. This type of cancer affects the throat area, including the base of the tongue and the tonsils.

Detecting the disease in its early stages is crucial, as early diagnosis can save lives and reduce the long-term effects of treatment. However, until now there has been no simple and effective test to identify HPV-related oropharyngeal cancer before it clinically manifests.

Scientists have been studying a possible solution: the detection of fragments of circulating HPV tumor DNA (ctHPVDNA), small portions of the virus's genetic material that can be released into the bloodstream by cancer cells.

These DNA fragments can function as a kind of biological “signature” of cancer, helping to identify the presence of the disease even before symptoms appear. The challenge is to discover if this viral DNA can actually be found in the blood years before diagnosis and if this would be reliable enough for a population screening test.

To investigate this possibility, researchers analyzed blood samples stored in a biobank (the biological sample bank of the MassGeneralBrigham network). These samples belonged to people who, years later, developed HPV-related oropharyngeal cancer.

In total, 28 patients with this type of cancer and 28 healthy people of the same sex and age range, who served as a comparison group, were studied. Interestingly, the blood of these people had been collected from 1.3 to 10.8 years before diagnosis.

The samples were analyzed “blindly,” meaning the scientists performing the tests did not know whether the blood came from someone sick or healthy, to avoid any kind of unconscious influence on the results.

Human Papillomavirus (HPV)

Researchers used a new type of highly accurate genetic test, called HPV whole genome sequencing liquid biopsy, capable of identifying several different characteristics of the virus within the DNA present in the blood. In addition, they also applied an HPV antibody test, which detects the body's immune response to the virus.

The results were encouraging. The DNA test detected signs of the virus in 22 of the 28 people who developed cancer, even years before diagnosis, in some cases up to 7.8 years before. In contrast, none of the 28 healthy volunteers tested positive, indicating that the test is extremely accurate and generates almost no false positives.

This means that the test correctly identified about 79% of real cases and was 100% accurate when the blood was from people without the disease.

The detection was even more reliable when the blood had been collected up to four years before diagnosis, a period in which the test was more sensitive than the antibody test. When researchers applied machine learning techniques (artificial intelligence), training a model with data from a second, larger sample of 306 people, the detection capability improved even further: the test correctly identified 27 out of 28 cases, with a sensitivity of 96%, and was able to predict the disease up to 10 years before diagnosis.

These findings suggest that circulating HPV tumor DNA in the blood may serve as a reliable marker for the early identification of oropharyngeal cancer caused by the virus. The discovery paves the way for the development of a screening test, similar to routine blood tests, that could be offered to people at higher risk of HPV infection.

In summary, the study shows that it is possible to detect biological signs of HPV-associated throat cancer many years before it appears, with high accuracy. In the future, combining this DNA test with other biomarkers, such as antibody tests, could allow doctors to diagnose the disease in its early stages, saving lives and avoiding aggressive treatments.

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Circulating tumor human papillomavirus DNA whole genome sequencing enables human papillomavirus-associated oropharynx cancer early detection

Dipon Das, Shun Hirayama, Ling Aye, Michael E Bryan, Saskia Naegele, Brian Zhao, Vasileios Efthymiou, Julia Mendel, Adam S Fisch, Zoe Guan, Lea Kröller, Birgitta E Michels, Tim Waterboer, Jeremy D Richmon, Viktor Adalsteinsson, Michael S Lawrence, Matthew G Crowson, A John Iafrate, and Daniel L Faden

JNCI: Journal of the National Cancer Institute. 10 September 2025, djaf249

DOI: 10.1093/jnci/djaf249

Abstract: 

Early detection of HPV-associated oropharyngeal cancer (HPV+OPSCC), the most common HPV cancer in the United States, could reduce disease-related morbidity and mortality, yet currently, there are no early detection tests. Circulating tumor HPV DNA (ctHPVDNA) is a sensitive and specific biomarker for HPV+OPSCC at diagnosis. It is unknown if ctHPVDNA is detectable prior to diagnosis, and thus it’s potential as an early detection test. Plasma samples from the MassGeneralBrigham biobank collected 1.3-10.8 years prior to diagnosis from HPV+OPSCC patients (n = 28) and age- and sex-matched controls (n = 28) were blinded and run on a newly developed and validated multi-feature HPV whole genome sequencing liquid biopsy assay and a validated HPV antibody assay. ctHPVDNA results were positive in 22/28 pre-diagnostic samples from HPV+OPSCC cases (sensitivity 79%) with a maximum lead time of 7.8 years. ctHPVDNA results were negative in all controls (0/28 controls, 100% specificity). Diagnostic accuracy was highest within four years of cancer diagnosis and was higher than HPV Ab detection within the same time frame (p-value 0.004). Application of a machine learning model trained and tested on an independent cohort of 306 cases and controls increased the sensitivity of detection to 27/28 cases (overall sensitivity 96%) and the maximum lead time to 10.3 years. Circulating tumor HPV DNA can be detected in the blood years prior to diagnosis with HPV+OPSCC, with high specificity, in a case-control cohort of 56 participants. ctHPVDNA detection alone, or in combination with previously identified serological biomarkers may be a feasible approach to early detection of HPV+OPSCC.