EBioMedicine (Dec 2022)
Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensificationResearch in context
- Peter Y.F. Zeng,
- Matthew J. Cecchini,
- John W. Barrett,
- Matthew Shammas-Toma,
- Loris De Cecco,
- Mara S. 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 Poh,
- Pinaki Bose,
- Joseph C. Dort,
- Mushfiq H. Shaikh,
- Sarah E.B. Ryan,
- Alice Dawson,
- Mohammed I. 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 S-C. Li,
- Paul C. Boutros,
- Joe S. Mymryk,
- Anthony C. Nichols
Affiliations
- Peter Y.F. Zeng
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada
- Matthew J. Cecchini
- Department of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada
- John W. Barrett
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada
- Matthew Shammas-Toma
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada
- Loris De Cecco
- Integrated Biology Platform, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
- Mara S. Serafini
- Integrated Biology Platform, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy
- Stefano Cavalieri
- Head and Neck Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
- Lisa Licitra
- Head and Neck Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
- Frank Hoebers
- Department of Radiation Oncology (MAASTRO), Research Institute GROW, Maastricht University, Maastricht, the Netherlands
- Ruud H. Brakenhoff
- Amsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, the Netherlands
- C. René Leemans
- Amsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, the Netherlands
- Kathrin Scheckenbach
- Department of Otolaryngology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Tito Poli
- Unit of Maxillofacial Surgery, Department of Medicine and Surgery, University of Parma—University Hospital of Parma, Parma, Italy
- Xiaowei Wang
- Department of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, Chicago, IL, USA
- Xinyi Liu
- Department of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, Chicago, IL, USA
- Francisco Laxague
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada
- Eitan Prisman
- Division of Otolaryngology- Head and Neck Surgery, Department of Surgery, Vancouver General Hospital, Vancouver, British Columbia, Canada
- Catherine Poh
- Division of Otolaryngology- Head and Neck Surgery, Department of Surgery, Vancouver General Hospital, Vancouver, British Columbia, Canada; Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
- Pinaki Bose
- Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Calgary, Calgary, Alberta, Canada
- Joseph C. Dort
- Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Calgary, Calgary, Alberta, Canada
- Mushfiq H. Shaikh
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada
- Sarah E.B. Ryan
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada
- Alice Dawson
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada
- Mohammed I. Khan
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada
- Christopher J. Howlett
- Department of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada
- William Stecho
- Department of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada
- Paul Plantinga
- Department of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada
- Sabrina Daniela da Silva
- Department of Otolaryngology Head and Neck Surgery, McGill University, Montreal, Quebec, Canada
- Michael Hier
- Department of Otolaryngology Head and Neck Surgery, McGill University, Montreal, Quebec, Canada
- Halema Khan
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada
- Danielle MacNeil
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada
- Adrian Mendez
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada
- John Yoo
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada
- Kevin Fung
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada
- Pencilla Lang
- Department of Oncology, University of Western Ontario, London, Ontario, Canada
- Eric Winquist
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada
- David A. Palma
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada
- Hedyeh Ziai
- Department of Otolaryngology - Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada
- Antonio L. Amelio
- Lineberger Comprehensive Cancer Center, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Cell Biology and Physiology, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Shawn S-C. Li
- Department of Biochemistry, University of Western Ontario, London, Ontario, Canada
- Paul C. Boutros
- Department of Human Genetics, University of California, Los Angeles, CA, USA; Department of Urology, University of California, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA; Institute for Precision Health, University of California, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, CA, USA
- Joe S. Mymryk
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada; Department of Microbiology & Immunology, University of Western Ontario, London, Ontario, Canada
- Anthony C. Nichols
- Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada; Corresponding author. Department of Otolaryngology - Head and Neck Surgery, Victoria Hospital, London Health Science Centre, Room B3-433A, 800 Commissioners Road East, London, ON, Canada N6A 5W9.
- Journal volume & issue
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Vol. 86
p. 104373
Abstract
Summary: Background: There is significant interest in treatment de-escalation for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) patients given the generally favourable prognosis. However, 15–30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to risk stratify HPV+ 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: A three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival compared to the immune desert (HR = 9.0, 95% CI: 3.2–25.5, P = 3.6 × 10−5) 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: With additional prospective validation, the UWO3 score could enable biomarker-driven clinical decision-making for patients with HPV+ 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.
