Arron, Sarah T.Wysong, AshleyHall, Mary A.Bailey, Christine N.Covington, Kyle R.Kurley, Sarah J.Goldberg, Matthew S.Kasprzak, Julia M.Somani, Ally-KhanIbrahim, Sherrif F.Brodland, David G.Cleaver, Nathan J.Maher, Ian A.Xia, YangKoyfman, Shlomo A.Newman, Jason G.2023-05-152023-05-152022-01-06Arron ST, Wysong A, Hall MA, et al. Gene expression profiling for metastatic risk in head and neck cutaneous squamous cell carcinoma. Laryngoscope Investig Otolaryngol. 2022;7(1):135-144. Published 2022 Jan 6. doi:10.1002/lio2.724https://hdl.handle.net/1805/32958Objective: 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.en-USAttribution-NonCommercial-NoDerivatives 4.0 InternationalCutaneous squamous cell carcinoma (cSCC)Gene expression profile (GEP)Head and neck cSCC (cSCC‐HN)High‐risk cSCCMetastasis riskArticle