HPV-negative head and neck cancers with adverse pathological features carry specific molecular changes that are associated with survival

Hugh Andrew Jinwook Kim; Peter Y F Zeng; Matthew Cecchini; Mushfiq Hassan Shaikh; Francisco Laxague; Xiaoxiao Deng; Laura Jarycki; Sarah Elizabeth Belle Ryan; Alice Dawson; Mu Han Liu; David A Palma; Krupal Patel; Neil Mundi; John W Barrett; Joe S Mymryk; Paul C Boutros; Anthony C Nichols

doi:10.1002/hed.27591

HPV-negative head and neck cancers with adverse pathological features carry specific molecular changes that are associated with survival

Head Neck. 2024 Feb;46(2):353-366. doi: 10.1002/hed.27591. Epub 2023 Dec 7.

Authors

Hugh Andrew Jinwook Kim¹, Peter Y F Zeng², Matthew Cecchini³, Mushfiq Hassan Shaikh², Francisco Laxague², Xiaoxiao Deng², Laura Jarycki², Sarah Elizabeth Belle Ryan^{2

3}, Alice Dawson^{2

3}, Mu Han Liu², David A Palma^{2

4}, Krupal Patel⁵, Neil Mundi⁶, John W Barrett^{2

4}, Joe S Mymryk^{2

4

7}, Paul C Boutros^{8

9

10

11

12}, Anthony C Nichols^{2

4}

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada.
² Department of Otolaryngology-Head and Neck Surgery, University of Western Ontario, London, Ontario, Canada.
³ Department of Pathology and Laboratory Medicine, University of Western Ontario, London, Ontario, Canada.
⁴ Department of Oncology, University of Western Ontario, London, Ontario, Canada.
⁵ Department of Otolaryngology-Head & Neck Surgery, Moffitt Cancer Center, Tampa, Florida, USA.
⁶ Department of Otolaryngology-Head & Neck Surgery, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
⁷ Department of Microbiology & Immunology, University of Western Ontario, London, Ontario, Canada.
⁸ Department of Human Genetics, University of California, Los Angeles, California, USA.
⁹ Department of Urology, University of California, Los Angeles, California, USA.
¹⁰ Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California, USA.
¹¹ Institute for Precision Health, University of California, Los Angeles, California, USA.
¹² Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, California, USA.

PMID: 38059331
DOI: 10.1002/hed.27591

Abstract

Background: Adverse pathological features following surgery in head and neck squamous cell carcinoma (HNSCC) are strongly associated with survival and guide adjuvant therapy. We investigated molecular changes associated with these features.

Methods: We downloaded data from the Cancer Genome Atlas and Cancer Proteome Atlas HNSCC cohorts. We compared tumors positive versus negative for perineural invasion (PNI), lymphovascular invasion (LVI), extracapsular spread (ECS), and positive margins (PSM), with multivariable analysis.

Results: All pathological features were associated with poor survival, as were the following molecular changes: low cyclin E1 (HR = 1.7) and high PKC-alpha (HR = 1.8) in tumors with PNI; six of 13 protein abundance changes with LVI; greater tumor hypoxia and high Raptor (HR = 2.0) and Rictor (HR = 1.6) with ECS; and low p38 (HR = 2.3), high fibronectin (HR = 1.6), low annexin A1 (HR = 3.1), and high caspase-9 (HR = 1.6) abundances with PSM.

Conclusions: Pathological features in HNSCC carry specific molecular changes that may explain their poor prognostic associations.

Keywords: TCGA; genomics; head and neck cancer; mutational status; pathology reports.

MeSH terms

Combined Modality Therapy
Head and Neck Neoplasms* / genetics
Humans
Papillomavirus Infections*
Prognosis
Squamous Cell Carcinoma of Head and Neck / genetics

Abstract

MeSH terms

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