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Originally published October 27, 2025
Last updated October 27, 2025
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Oropharyngeal squamous cell carcinoma (OPSCC) caused by human papillomavirus (HPV) is on the rise. More patients are undergoing treatment for this type of throat cancer, including surgery, radiation therapy and chemotherapy. After treatment, some patients inevitably see cancer remain or return. Finding biomarkers to accurately detect the presence of cancer, in a minimally invasive way, is an active area of research.
One biomarker researchers are investigating is circulating HPV DNA (HPV ctDNA). Daniel Kwon, MD, is a head and neck surgeon with the USC Head and Neck Center, part of Keck Medicine of USC. Kwon and his colleagues at the USC Head and Neck Center, whose specialists come from the USC Caruso Department of Otolaryngology – Head and Neck Surgery and the USC Norris Comprehensive Cancer Center, both part of Keck Medicine, have been investigating better ways to detect throat cancer caused by HPV, including blood tests and liquid biopsies. They have also conducted research on public awareness of the association between HPV and throat cancer.
Ahead, Kwon discusses what research on HPV ctDNA has shown so far.
As Kwon explains, initial treatment for throat cancer varies, ranging from minimally invasive transoral robotic surgery to traditional open surgery if necessary, as well as chemoradiation. After treatment, patients are monitored for any remaining cancer.
“Historically, we’ve had to just wait and see if the cancer came back with exams and imaging. There wasn’t a very good way to tell if the treatment had worked,” Kwon says. “These days, blood tests are being developed to help assess the treatment response more in real time. Initial studies show that circulating HPV DNA in the blood correlates with the disease burden in the body.”
Testing for HPV ctDNA would be a more proactive way of detecting cancer. Researchers hope that this liquid biomarker could one day serve as a fast, minimally invasive way to assess for cancer before, during and after a patient’s cancer treatment, thereby providing patients and their physicians with additional information on which to base future treatment plans.
“For example,” Kwon says, “even a few days after surgery, you can see the level of circulating HPV DNA decline, telling you whether the surgery was successful or not.”
Researchers are studying how early results of these blood tests can help chart next steps for treatment. “Knowing early helps us pivot more quickly,” Kwon says. Early testing may be able to guide the use of additional treatment including additional surgery, radiation, immunotherapy or chemotherapy, he says.
Testing for HPV ctDNA could also give doctors more insight to allow them to better customize treatment to each individual, not subjecting patients who don’t need it to unnecessary treatments and subsequent toxicities.
More research needs to be done to validate HPV ctDNA as a biomarker. Assays for quantifying HPV DNA also need to be scientifically validated and fit for this purpose. This work is ongoing.
“Because this is all very new, there aren’t completely agreed-upon ways to utilize this information,” Kwon says. He adds that other types of blood tests similar to HPV ctDNA tests are also being investigated for other types of head and neck cancers.
These blood tests, he says, would significantly strengthen the toolbox for head and neck cancer treatment beyond what currently exists. “Obviously, we still have imaging and clinical exams, but blood tests may become the most important tool of all because they’re the most sensitive and can be specific to each type of cancer,” Kwon says.
More choices for treatment as also means more nuance and shared decision-making. “Back in the day, treatment was basically, ‘Hey, you have this tumor. We’re either going to cut it out or shoot it with radiation,’” Kwon says. “It was pretty straightforward.”
He continues: “Having more sophisticated tools such as circulating tumor DNA tests, will require a lot more counseling and patient involvement in making subsequent treatment decisions.”
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