Gene expression profiling for metastatic risk in head and neck cutaneous squamous cell carcinoma

Sarah T. Arron, Ashley Wysong, Mary A. Hall, Christine N. Bailey, Kyle R. Covington, Sarah J. Kurley, Matthew S. Goldberg, Julia M. Kasprzak, Ally Khan Somani, Sherrif F. Ibrahim, David G. Brodland, Nathan J. Cleaver, Ian A. Maher, Yang Xia, Shlomo A. Koyfman, Jason G. Newman

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Objective: Over 50% of newly diagnosed cutaneous squamous cell carcinoma (cSCC) lesions occur in the head and neck (cSCC-HN), and metastasis to nodal basins in this region further complicates surgical and adjuvant treatment. The current study addressed whether the 40-gene expression profile (40-GEP) test can predict metastatic risk in cSCC-HN with improved accuracy and provide independent prognostic value to complement current risk assessment methods.

Study Design: Multicenter, retrospective cohort study.

Methods: Formalin-fixed paraffin-embedded primary tumor tissue and associated clinical data from patients with cSCC-HN ( n = 278) were collected from 33 independent centers. Samples were analyzed via the 40-GEP test. Cases were staged per American Joint Committee on Cancer, Eighth Edition (AJCC8) and Brigham and Women's Hospital (BWH) criteria after comprehensive medical record and pathology report review. Metastasis-free survival (MFS) rates were determined, and risk factors were analyzed via Cox regression.

Results: The 40-GEP test classified the cohort into low (Class 1, n = 126; 45.3%), moderate (Class 2A, n = 134; 48.2%), and high (Class 2B, n = 18; 6.5%) metastatic risk at 3 years postdiagnosis. Regional/distant metastasis occurred in 54 patients (19.4%). MFS rates were 92.1% (Class 1), 76.1% (Class 2A), and 44.4% (Class 2B; p < .0001). Multivariate analysis of 40-GEP results with AJCC8 or BWH tumor stage, or clinicopathologic risk factors, demonstrated independent prognostic value of the 40-GEP test ( p < .03). Accuracy of predicting metastatic risk was also improved using 40-GEP classification ( p < .02).

Conclusions: Improved metastatic risk stratification through the 40-GEP test could complement cSCC-HN risk assessment for better-informed decision-making for treatment and surveillance and ultimately improve patient outcomes.

Level of Evidence: 3.

Original languageEnglish (US)
Pages (from-to)135-144
Number of pages10
JournalLaryngoscope investigative otolaryngology
Issue number1
StatePublished - Feb 2022

Bibliographical note

Funding Information:
Sarah T. Arron is an employee of Rakuten Medical and is a consultant for Castle Biosciences and Enspectra Health. Ashley Wysong is a board member for the American College of Mohs Surgery, Women's Dermatologic Society, and Dermatology Foundation and is the principal investigator on an institutional research grant from Castle Biosciences. Mary A. Hall, Christine N. Bailey, Kyle R. Covington, Sarah J. Kurley, and Matthew S. Goldberg are employees and option holders for Castle Biosciences, Inc. Sherrif F. Ibrahim has received advisor fees from Castle Biosciences, Regeneron Pharmaceuticals, and Sun Pharmaceutical Industries; research funding from Castle Biosciences, Galderma, and Regeneron Pharmaceuticals; and speaker fees from Castle Biosciences, Galderma, Genentech, Regeneron Pharmaceuticals, and Sun Pharmaceutical Industries. Shlomo A. Koyfman received research funding and consulting fees from Merck, research funding from Bristol Myers Squibb, and honoraria from UpToDate. Jason G. Newman is a consultant for Bolder Surgical, Inc. and Medtronic, Inc. and a steering committee member for Castle Biosciences The remaining authors served as investigators for this study, and there are no further conflicts to disclose.

Publisher Copyright:
© 2022 Castle Biosciences, Inc. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.


  • cutaneous squamous cell carcinoma (cSCC)
  • gene expression profile (GEP)
  • head and neck cSCC (cSCC-HN)
  • high-risk cSCC
  • metastasis risk

PubMed: MeSH publication types

  • Journal Article


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