The demographics of head and neck cancer patients are changing, and researchers at the University of Maryland Marlene and Steward Greenebaum Comprehensive Cancer Center (UMGCCC) are leading the way. Investigators from UMGCCC presented surprising findings of the E3311 study – a phase II trial of transoral surgery (TOS) followed by pathology-based adjuvant treatment in HPV-associated (HPV+) oropharynx cancer (OPC), sponsored by the ECOG-ACRIN Cancer Research Group – during the head and neck poster session at the American Society of Clinical Oncology's (ASCO) annual meeting on June 6, 2022.

A New Demographic

Oropharyngeal squamous cell carcinoma has grown increasingly prevalent, largely due to increasing numbers of adults with human papillomavirus (HPV). "A significant portion of our patients are presenting with HPV+ oropharynx cancer," said Ranee Mehra, MD, who served as the medical oncology co-chair of the E3311 trial.

This patient population has a distinct demographic profile that diverges from the typical head and neck cancer patient, who is older and has a history of heavy tobacco and alcohol use, along with a higher incidence of comorbidities.

"Some of the HPV+ oropharynx cancer patients also have smoking as a risk factor, but many are nonsmokers. A majority of them are men, and they tend to be younger and healthier," Dr. Mehra said. "These patients tend to have a great prognosis, and the goal of treatment is cure."

Surprising Findings From Deintensification Research

Given the strong prognosis for many people with HPV+ oropharynx squamous cell carcinoma, one fruitful area for current research studies focuses on ways to deintensify treatment and reduce side effects. The current standard of care was developed when the typical oropharynx cancer patient had developed tobacco- and alcohol-related cancer. The current treatment methodology may be too aggressive for many HPV+ oropharynx cancer patients.

The E3311 study investigated a strategy for deintensification based on two factors:

Performing transoral resection
Thirty years ago, surgery for oropharynx cancer required surgeons to split the jaw to gain access to the tumor. Instead, most oncology teams chose to pursue treatment plans that combined chemotherapy and radiation. These plans eliminated the obvious drawbacks of surgery, but they also exposed patients to acute side effects and late effects of radiation therapy.

Today, it is more feasible for head and neck surgeons to perform transoral resections. In fact, the University of Maryland Medical Center's Chief Executive Officer, Bert O'Malley, MD, pioneered some of the transoral techniques and technologies that make this possible.

In the E3311 trial of more than 350 people with HPV+ oropharynx cancer, patients underwent transoral resection. Then, adjuvant treatment was selected based on the patient's pathology. The low-risk patient group had no further treatment, the high-risk group had chemotherapy and radiation, and the third group had randomized standard or low-dose radiation.

Investigating Smoking Outcomes
Another question Dr. Mehra and her fellow researchers investigated was whether a patient's significant smoking history (10 pack years or more) should play a role in deciding whether to pursue transoral resection or chemotherapy and radiation. While in prior studies, patients with a 10-pack-year or greater smoking history did not do as well with chemotherapy and radiation, the distinction in E3311’s findings was that smoking was not prognostic.

"In this approach, smokers with greater versus less than 10 pack years smoking histories had the same rate of progression free survival at three years, with similar survival rates," Dr. Mehra said. "Pathologic high-risk features that we typically see (extranodal extension, positive margins) were not seen at a greater rate in people with significant smoking histories, and we also did not see a difference in outcomes in this group based in the smoking history."

The findings were surprising. "I think in head and neck oncology, we have adopted the idea that those who are smokers do not do as well with deintensified treatment, and smokers are sometimes excluded from trials because of it," Dr. Mehra said. "These results, from a large sample size, bring those assumptions into question."

The head and neck oncology research team at UMGCCC is using these findings to plan future research studies. The University of Maryland Greenebaum Comprehensive Cancer Center is an ideal site to continue research that has the potential to redraw the lines governing the field's understanding of head and neck cancers. UMGCCC is No. 1  in Maryland for head and neck cancer surgery and specializes in HPV+ oropharynx cancer. The dedicated, multidisciplinary head and neck team at University of Maryland Medical Center has several ongoing clinical trials and research projects, studying promising new medical and surgical approaches to treatment.

"The robust team at UMGCCC takes a multidisciplinary approach, bringing a range of experts to the table to design the best treatment for each patient. This study is emblematic of our personalized and innovative approach at UMGCCC," Dr. Mehra said.

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