Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensification

Peter YF. Zeng(Western University), Matthew J. Cecchini(Western University), John W. Barrett(Western University), Matthew Shammas‐Toma(Western University), Loris De Cecco(Fondazione IRCCS Istituto Nazionale dei Tumori), Mara Serena Serafini(Fondazione IRCCS Istituto Nazionale dei Tumori), Stefano Cavalieri(University of Milan), Lisa Licitra(University of Milan), Frank Hoebers(Maastricht University), Ruud H. Brakenhoff(Amsterdam University Medical Centers), C. René Leemans(Amsterdam University Medical Centers), Kathrin Scheckenbach(Heinrich Heine University Düsseldorf), Tito Poli(University of Parma), Xiaowei Wang(University of Illinois Chicago), Xinyi Liu(University of Illinois Chicago), Francisco Laxague(Western University), Eitan Prisman(Vancouver General Hospital), Catherine F. Poh(University of British Columbia), Pinaki Bose(University of Calgary), Joseph C. Dort(University of Calgary), Mushfiq Hassan Shaikh(Western University), Sarah E.B. Ryan(Western University), Alice Dawson(Western University), Mohammed Imran Khan(Western University), Christopher J. Howlett(Western University), William Stecho(Western University), Paul Plantinga(Western University), Sabrina Daniela da Silva(McGill University), Michael Hier(McGill University), Halema Khan(Western University), Danielle MacNeil(Western University), Adrian Mendez(Western University), John Yoo(Western University), Kevin Fung(Western University), Pencilla Lang(Western University), Eric Winquist(Western University), David A. Palma(Western University), Hedyeh Ziai(University of Toronto), Antonio L. Amelio(University of North Carolina at Chapel Hill), Shawn Li(Western University), Paul C. Boutros(University of California, Los Angeles), Joe S. Mymryk(Western University), Anthony C. Nichols(Western University)
EBioMedicine
November 25, 2022
10.1016/j.ebiom.2022.104373
Cited by 36Open Access
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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.

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