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Immune-based classification of HPV-associated oropharyngeal cancer with implications for biomarker-driven treatment de-intensification.
| Content Provider | Europe PMC |
|---|---|
| Author | Zeng, Peter Y.F. Cecchini, Matthew J. Barrett, John W. Shammas-Toma, Matthew De Cecco, Loris Serafini, Mara S. Cavalieri, Stefano Licitra, Lisa Hoebers, Frank Brakenhoff, Ruud H. Leemans, C. René Scheckenbach, Kathrin Poli, Tito Wang, Xiaowei Liu, Xinyi Laxague, Francisco Prisman, Eitan Poh, Catherine Bose, Pinaki Dort, Joseph C. Shaikh, Mushfiq H. Ryan, Sarah E.B. Dawson, Alice Khan, Mohammed I. Howlett, Christopher J. Stecho, William Plantinga, Paul Daniela da Silva, Sabrina Hier, Michael Khan, Halema MacNeil, Danielle Mendez, Adrian Yoo, John Fung, Kevin Lang, Pencilla Winquist, Eric Palma, David A. Ziai, Hedyeh Amelio, Antonio L. Li, Shawn S-C. Boutros, Paul C. Mymryk, Joe S. Nichols, Anthony C. |
| Copyright Year | 2022 |
| Abstract | SummaryBackgroundThere 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.MethodsWe 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.FindingsA 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.InterpretationWith 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.FundingCIHR, European Union, and the NIH. |
| Related Links | https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC9706534&blobtype=pdf |
| Journal | eBioMedicine |
| Volume Number | 86 |
| DOI | 10.1016/j.ebiom.2022.104373 |
| PubMed Central reference number | PMC9706534 |
| PubMed reference number | 36442320 |
| e-ISSN | 23523964 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2022-11-25 |
| Access Restriction | Open |
| Rights License | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). © 2022 The Author(s) |
| Subject Keyword | Head and neck squamous cell carcinoma Transcriptomics Biomarkers Cancer immunology HPV De-escalation |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Biochemistry, Genetics and Molecular Biology |
