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. Now, researchers are investigating whether some patients can safely avoid additional treatment while maintaining excellent cancer outcomes.
A team of head and neck cancer physicians at MUSC Hollings Cancer Center launched the OPERATION clinical trial to explore that possibility. 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.
“These patients do really well, and they live a long time after treatment,” said Bhisham Chera, MD, a radiation oncologist at Hollings and co-principal investigator of the trial. “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, or HPV, are among the most common and fastest-growing head and neck cancers in the U.S. Unlike cancers caused by tobacco or alcohol, HPV-related throat cancers tend to respond well to treatment, creating an opportunity to rethink whether every patient needs the same approach.
Currently, only about 10% to 15% of patients with HPV-related throat cancer avoid radiation after surgery. The OPERATION trial is investigating whether more patients can skip radiation and instead be closely monitored, with treatment reserved for those whose cancer returns.
“We think we could avoid radiation in 70% to 80% of patients overall,” Chera said. “That’s a big deal. And should the cancer recur, we know radiation is effective, so we’ll give it then.”
Using blood tests and pathology to personalize cancer care
The trial is enrolling adults with HPV-related throat cancer who are good candidates for minimally invasive robotic surgery, which allows surgeons to remove tumors through the mouth without making large incisions.
Central to the trial is NavDx, a blood test that Chera helped to develop, which detects circulating tumor DNA, or ctDNA—tiny fragments of DNA released by HPV-related cancer cells. These traces identify signs that cancer remains after treatment or has returned.
Although NavDx is already used to monitor patients for cancer recurrence, the OPERATION trial is investigating whether it can also guide treatment decisions immediately after surgery.
“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. “It tells you how the cancer is responding to treatment much better than imaging.”
We think we could avoid radiation in 70% to 80% of patients overall. That’s a big deal. And should the cancer recur, we know radiation is effective, so we’ll give it then.
Bhisham Chera
Alexandra Kejner, MD, a head and neck surgeon and co-principal investigator of the trial, said advances in ctDNA testing are allowing physicians to detect cancer-related changes earlier and personalize treatment accordingly.
“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.”
Patients receive the 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.
The blood test is only one part of the decision-making process. A team of pathologists specializing in head and neck cancer carefully examine the removed tumors for features that indicate whether cancer is likely to return. Together, the pathology findings and blood test help physicians to determine which patients may safely avoid additional treatment.
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 taste, difficulty swallowing or talking, jaw stiffness, tissue scarring, and dental problems.
By identifying patients who may not need radiation, the researchers hope to reduce these complications without compromising cancer outcomes.
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 better understand how different treatment approaches affect patients, the team is 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, avoiding radiation does not mean less follow-up. Patients will be monitored closely for several years through regular blood tests, imaging, and follow-up visits. They also have access to the Hollings Head and Neck Cancer Survivorship Clinic, which helps patients manage long-term side effects, restore normal function and stay on track with recommended health screenings.
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.
At the end of the day, it’s a cancer vaccine. Anything we can do to prevent these cancers in the first place is a huge win.
Alexandra Kejner
As a National Cancer Institute-designated cancer center, Hollings is helping to advance this approach through investigator-initiated clinical trials like this one that address questions arising directly from physicians’ experiences caring for 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, preventing those cancers remains the ultimate goal. 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 significantly reduce oral HPV infections.
“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.”
The author is the communications manager at MUSC Hollings Cancer Center
