Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensification
Peter YF. Zeng, Matthew J. Cecchini, John W. Barrett, Matthew Shammas‐Toma, Loris De Cecco, Mara Serena Serafini, Stefano Cavalieri, Lisa Licitra, Frank Hoebers, Ruud H. Brakenhoff, C. René Leemans, Kathrin Scheckenbach, Tito Poli, Xiaowei Wang, Xinyi Liu, Francisco Laxague, Eitan Prisman, Catherine F. Poh, Pinaki Bose, Joseph C. Dort, Mushfiq Hassan Shaikh, Sarah E.B. Ryan, Alice Dawson, Mohammed Imran Khan, Christopher J. Howlett, William Stecho, Paul Plantinga, Sabrina Daniela da Silva, Michael Hier, Halema Khan, Danielle MacNeil, Adrian Mendez, John Yoo, Kevin Fung, Pencilla Lang, Eric Winquist, David A. Palma, Hedyeh Ziai, Antonio L. Amelio, Shawn Li, Paul C. Boutros, Joe S. Mymryk, Anthony C. Nichols
Abstract
BACKGROUND: OPSCC patients. METHODS: We created an immune score (UWO3) associated with survival outcomes in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes. FINDINGS: ) and mixed (HR = 6.4, 95% CI: 2.2-18.7, P = 0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two small treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation. INTERPRETATION: OPSCC based on robust outcome prediction across six independent cohorts. Prospective de-escalation and intensification clinical trials are currently being planned. FUNDING: CIHR, European Union, and the NIH.