40-GEP Assists in Determining Prognosis of Head and Neck Cutaneous Squamous Cell Carcinoma

Arron ST, Wysong A, Hall MA, Bailey CN, Covington KR, Kurley SJ, Goldberg MS, Kasprzak JM, Somani AK, Ibrahim SF, Brodland DG, Cleaver NJ, Maher IA, Xia Y, Koyfman SA, Newman JG. Gene expression profiling for metastatic risk in head and neck cutaneous squamous cell carcinoma. Laryngoscope Investig Otolaryngol. 2022 Jan 6;7(1):135-144. doi: 10.1002/lio2.724. PMID: 35155791; PMCID: PMC8823155.

Clinical Pearls

• This study aimed to determine the prognostic value and accuracy of a 40-gene expression profile (40-GEP) test in the management of cutaneous head and neck squamous cell carcinoma

• There were 33 clinical centers involved in this retrospective cohort study with 278 tissues samples used with associated clinical data. When clinicopathologic factors were included in multivariate analysis with 40-GEP Class, the 40-GEP class 2a (HR = 2.28, p = .0311) and 2b (HR = 4.05, p = .0134) were found to be significant indicators of metastatic risk.

• The results of this study supported the use of a 40-gene expression profile test in assessing metastatic risk of cutaneous squamous cell carcinoma of the head and neck.

Discussion:

This was a multi-center, retrospective cohort study aimed towards determining whether a 40-gene expression profile (40-GEP) can predict metastatic risk in cutaneous head and neck squamous cell carcinoma with improved accuracy and provide independent prognostic value to complement current risk assessment methods

278 tissue samples from primary tumors and their associated clinical data were obtained from 33 clinical centers in this study. The 40-GEP was used to classify each sample based on risk for metastasis at 3 years post-diagnosis as either Class 1 (low-risk), Class 2a (moderate-risk), or Class 2b (high-risk). Each sample and associated data was also staged via AJCC8 and BWH tumor staging systems and were subsequently classified as either low-risk, high-risk, or very high-risk per the current NCCN guidelines. Finally, sensitivity, specificity, PPV, and NPV for each sample as well as hazard ratios and metastasis-free survival were calculated.

The results of this study found a significant association between both the NCCN risk status and 40-GEP test classification with patients having metastatic events or not, indicating both modalities of classification are effective. Moreover, the sensitivity of the 40-GEP test in those classified as Class 2 (moderate-risk) (79.6%) significantly increased when compared to the sensitivity with AJCC8 T3/T4 (37.0%) staging and BWH T2b/T3 (29.6%; p < 0.0001). Additionally, the hazard ratios for 40-GEP class 2b were found to be significant (HR=9.07, p<0.001 and HR=2.88, p=0.0025 respectively). When clinicopathologic factors were included in multivariate analysis with 40-GEP Class, the 40-GEP class 2a (HR = 2.28, p = .0311) and 2b (HR = 4.05, p = .0134) were found to be significant indicators of metastatic risk.

Overall, this study supported the utility and prognostic use of a 40-gene expression profile in the use of metastatic cutaneous squamous cell carcinoma of the head and neck.