Clinical trial aims to personalize treatment for patients with HPV-related throat cancer

For patients with an HPV-related form of throat cancer, treatment is often highly effective, with cure rates as high as 90%, depending on the disease stage. Because these cancers respond so well to treatment, researchers are investigating whether some patients can safely avoid additional treatment while maintaining excellent cancer outcomes and reducing long-term side effects.

With this in mind, a team of head and neck cancer physicians at MUSC Hollings Cancer Center developed the OPERATION clinical trial. By combining minimally invasive robotic surgery with a blood test that detects tiny amounts of cancer-related DNA, the team hopes to identify patients who can safely avoid radiation therapy after surgery without increasing their risk of the cancer returning.

“These patients do really well, and they live a long time after treatment,” said Bhisham Chera, M.D., a radiation oncologist at Hollings who helped develop the blood-based technology used in the trial and now serves as its co-principal investigator. “We’re trying to figure out what is the minimum amount of treatment required to achieve excellent cancer outcomes while preserving their quality of life.”

Moving beyond a one-size-fits-all approach

Throat cancers caused by the human papillomavirus virus, or HPV, are among the most common and fastest-growing head and neck cancers in the U.S. Unlike those caused by tobacco or alcohol, HPV-related throat cancers tend to respond well to treatment, creating an opportunity to determine whether every patient needs to be treated the same way.

Currently, only about 10% to 15% of patients with HPV-related throat cancer avoid radiation after surgery. In the OPERATION trial, researchers are investigating whether some patients can skip radiation therapy altogether and instead be closely monitored, with radiation used only if their cancer returns. If successful, the approach could spare many patients from unnecessary treatment and improve their quality of life.

“We think we could avoid radiation in maybe 70% to 80% of patients overall,” Chera said. “That’s a big deal. And should the cancer recur, it’s not the end of the world. We know radiation is effective, so we’ll give it then.”

Using blood tests and expert pathology to personalize cancer care

Not every patient is a candidate for this approach. The trial is enrolling adults with HPV-related throat cancer, medically known as oropharyngeal squamous cell carcinoma, who are good candidates for minimally invasive robotic surgery, a technique that allows surgeons to access and remove tumors through the mouth without making large incisions.

Central to the trial is NavDx, a blood test that detects circulating tumor DNA, or ctDNA – tiny fragments of DNA released specifically by HPV-related cancer cells. These traces give doctors another way to look for signs that cancer remains after treatment or has returned.

For Chera, the OPERATION trial builds on nearly a decade of work helping to advance the technology behind the test. Beginning in 2016, he worked with colleagues to develop a method for detecting HPV-related cancer DNA in the bloodstream and is a co-inventor of the technology that was later licensed and commercialized as NavDx.

Now, Chera and the team are taking that work a step further. While NavDx is already used to monitor patients for signs that their cancer has returned, the OPERATION trial is studying whether it can also guide treatment decisions immediately after surgery – potentially identifying patients who can safely avoid radiation therapy.

“It’s a very sensitive and specific test – more sensitive and specific than a PET scan, a CT scan or an MRI at detecting cancer,” Chera explained of NavDx. “It tells you how the cancer is responding to treatment much better than imaging.”

Alexandra Kejner, M.D., a head and neck surgeon and co-principal investigator of the trial, said advances in ctDNA testing are allowing doctors to rethink cancer treatment.

“Until recently, the only way we were able to tell if somebody had a recurrence was if a tumor showed up on examination or imaging,” Kejner said. “Now we’re able to detect these changes earlier and use that information to design treatments around the patient. For this trial, the only thing we’re adding is a blood test that we’re doing anyway as a part of normal surveillance but utilizing it to inform adjuvant treatment selection.”

Patients in the trial receive the ctDNA blood test before and after surgery. If no cancer-related DNA is detected after surgery and there are no high-risk pathological features, patients are closely monitored rather than moving directly to radiation. Should the cancer return, radiation remains an effective treatment option with a high likelihood of successfully treating the disease.

The blood test is one piece of the decision-making process. The second piece depends on a careful examination of the tumor after surgery. Mary Richardson, M.D., D.D.S., who specializes in head and neck cancer pathology, and her team look for signs that help to determine how likely the cancer is to return and whether additional treatment is needed. Combined with ctDNA testing, their expertise allows physicians to identify patients who are good candidates to move forward with the trial.

Improving quality of life after cancer treatment

Radiation therapy for head and neck cancer can significantly affect quality of life during and long after treatment. Possible side effects include dry mouth, changes in or loss of taste, difficulty swallowing or talking, jaw stiffness, tissue scarring and dental problems.

While reducing treatment intensity is a major goal of the study, the researchers are equally focused on helping patients to return to their daily lives. To understand more fully how different treatment approaches affect quality of life, they are collecting information on swallowing, pain and other patient-reported outcomes.

“This will give us more data and help reduce some of the treatment burden that patients have from this type of disease,” Kejner said.

Importantly, omitting radiation does not mean doing less follow-up. Patients in the trial will be monitored closely for several years through regular blood tests, imaging and follow-up visits. They are also supported through the Hollings Head and Neck Cancer Survivorship Clinic, which works with patients to manage long-term side effects, restore normal function and stay on track with recommended health screenings as they move forward after cancer treatment.

Advancing cancer care through clinical trials

The OPERATION trial reflects a growing movement in cancer care toward treatment de-escalation – providing patients with the treatment they need while avoiding unnecessary therapies whenever possible. As a National Cancer Institute-designated cancer center, Hollings is among the centers leading the way in this movement. Hollings physicians and researchers use investigator-initiated clinical trials to improve cancer treatment – asking questions that arise directly from their experiences with patients.

“Clinical trials are one of the major ways we offer patients innovative treatments,” Chera said. “Patients who participate help themselves, but they’re also helping future patients. They’re paying it forward.”

Although researchers are working to improve treatment for HPV-related cancers, they emphasize that preventing those cancers before they start is the best outcome of all. HPV vaccination is the most effective way to reduce the risk of HPV-associated cancers, including cancers of the throat, cervix and other parts of the body. The vaccine is approved for adults up to age 45 and has been shown to reduce oral HPV infections significantly.

“At the end of the day, it’s a cancer vaccine,” Kejner said. “Anything we can do to prevent these cancers in the first place is a huge win.”