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

Autor:	Zeng PYF; 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., Cecchini MJ; Department of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada., Barrett JW; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada., Shammas-Toma M; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada., De Cecco L; Integrated Biology Platform, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy., Serafini MS; Integrated Biology Platform, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy., Cavalieri S; 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., Licitra L; 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., Hoebers F; Department of Radiation Oncology (MAASTRO), Research Institute GROW, Maastricht University, Maastricht, the Netherlands., Brakenhoff RH; Amsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, the Netherlands., Leemans CR; Amsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology/Head and Neck Surgery, Cancer Center Amsterdam, the Netherlands., Scheckenbach K; Department of Otolaryngology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Poli T; Unit of Maxillofacial Surgery, Department of Medicine and Surgery, University of Parma-University Hospital of Parma, Parma, Italy., Wang X; Department of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, Chicago, IL, USA., Liu X; Department of Pharmacology and Regenerative Medicine, The University of Illinois at Chicago, Chicago, IL, USA., Laxague F; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada., Prisman E; Division of Otolaryngology- Head and Neck Surgery, Department of Surgery, Vancouver General Hospital, Vancouver, British Columbia, Canada., Poh C; 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., Bose P; Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Calgary, Calgary, Alberta, Canada., Dort JC; Division of Otolaryngology - Head and Neck Surgery, Department of Surgery, University of Calgary, Calgary, Alberta, Canada., Shaikh MH; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada., Ryan SEB; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada., Dawson A; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada., Khan MI; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada., Howlett CJ; Department of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada., Stecho W; Department of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada., Plantinga P; Department of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada., Daniela da Silva S; Department of Otolaryngology Head and Neck Surgery, McGill University, Montreal, Quebec, Canada., Hier M; Department of Otolaryngology Head and Neck Surgery, McGill University, Montreal, Quebec, Canada., Khan H; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada., MacNeil D; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada., Mendez A; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada., Yoo J; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada., Fung K; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada., Lang P; Department of Oncology, University of Western Ontario, London, Ontario, Canada., Winquist E; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada., Palma DA; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada., Ziai H; Department of Otolaryngology - Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada., Amelio AL; 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., Li SS; Department of Biochemistry, University of Western Ontario, London, Ontario, Canada., Boutros PC; 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., Mymryk JS; 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., Nichols AC; Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada; Department of Oncology, University of Western Ontario, London, Ontario, Canada. Electronic address: anthony.nichols@lhsc.on.ca.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2022 Dec; Vol. 86, pp. 104373. Date of Electronic Publication: 2022 Nov 25.
DOI:	10.1016/j.ebiom.2022.104373
Abstrakt:	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. Competing Interests: Declaration of interests PYFZ, JWB, PCB, JSM and ACN have a US patent pending for the UWO3 score. All other authors declare no conflict of interest. (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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