By Sung Jun Ma, MD, James Cancer Hospital and Solove Research Institute, Ohio State University Comprehensive Cancer Center
James Bates, MD, a radiation oncologist at the Winship Cancer Institute of Emory University, in collaboration with other colleagues from Vanderbilt University Medical Center and University of North Carolina, presented early results from their multicenter, phase II prospective clinical trial during the Plenary II session at the 2026 Multidisciplinary Head and Neck Cancers Symposium. It evaluated the role of circulating tumor human papillomavirus DNA (ctHPVDNA) in de-intensifying adjuvant treatments among patients with early-stage HPV-related oropharyngeal cancer who received transoral robotic surgery (TORS). This report is the second futility analysis after the 30th patient reached six months of follow up.
In this phase II trial, eligible patients were those with baseline detectable ctHPVDNA, no or limited smoking history, and pT0-2N0-1 HPV-related oropharyngeal cancer who received TORS and neck dissection with close margin, perineural invasion, 2-4 positive lymph nodes, or a single lymph node (>3 cm). Patients were ineligible if they had high-risk findings such as extranodal extension or positive margin. Postoperative ctHPVDNA was drawn approximately two weeks after surgery. If postoperative ctHPVDNA was undetectable, adjuvant radiation was de-intensified with 36 Gy in 15 fractions; if detectable, then adjuvant radiation was standard-of-care dose fractionation (50-60 Gy in 25-30 fractions). In addition, for those with final surgical margin greater than 2 mm, primary site postoperative bed was omitted in radiation fields.
When the first 30 patients were enrolled and evaluated, the majority of them were male with pT1N1 disease and undetectable postoperative ctHPVDNA after surgery. There were 40% of patients who achieved more than 2 mm surgical margin and did not receive adjuvant radiation to the primary site postoperative bed. Median follow-up was 13 months. Overall, one-year locoregional control and progression-free survival outcomes were favorable with 95.5% and 89.0%, respectively. Authors noted that there were two patient deaths unrelated to their head and neck cancer, which in part affected the overall progression-free survival outcome in this cohort.
This study by Dr. Bates and colleagues highlights the feasibility of the personalized, ctHPVDNA-guided treatment de-intensification among intermediate-risk patients with HPV-related head and neck cancer undergoing TORS and neck dissection. In particular, this phase II trial demonstrated the promise of shortening adjuvant radiation to three weeks for a select group of patients and provides further data that primary site postoperative bed region can be safely omitted in radiation fields in certain patients. However, as this is only an interim analysis, complete follow-up and further, larger studies are needed to confirm these findings. Such findings add an important insight to the growing body of literature evaluating the role of hypofractionated radiation and other de-escalation strategies for patients undergoing TORS.
“While complete analysis of the full study and subsequent larger, randomized studies are needed to fully ensure the safety of de-escalation of adjuvant therapy in this patient population, the role of ctHPVDNA as a marker of molecular residual disease is very promising,” said Dr. Bates, the presenting author for this phase II trial.
“Patients with HPV-related oropharyngeal cancer in the future may be able to undergo more personalized treatment courses to best balance an optimal chance of curing cancer while minimizing the significant burden of toxicity of our treatment modalities.”
Though early findings of this phase II trial demonstrated favorable oncologic and survival outcomes, Dr. Bates also noted that careful patient selection is still crucial when considering de-intensified treatments.
“This study continues to support that a population of patients with HPV-related oropharyngeal cancer do well with various forms of de-escalated therapies, but still emphasizes that there is a smaller population of patients who do not experience these excellent outcomes. It emphasizes that we are not yet perfect at identifying patients which patients fall into which bucket and underscores the need for more precise methods to identify those patients with more aggressive tumors who may need more aggressive treatments.”
In summary, the multicenter phase II trial presented by Dr. Bates and colleagues is significant for its contribution to our evolving treatment de-intensification strategies, highlighting the role of postoperative ctHPVDNA to guide patient selection. This study’s early findings provide valuable insight and guidance on the design of future prospective studies incorporating ctHPVDNA, and long-term outcomes are eagerly awaited.
Published February 21, 2026
