Sex Differences in Using Systemic Inflammatory Markers to Prognosticate Patients with Head and Neck Squamous Cell Carcinoma.

ABSTRACT

Background: Remarkable discrepancy exists in outcomes between men and women for multiple malignancies. We sought to expose sex differences in using platelet count and neutrophil-to-lymphocyte ratio (NLR) to predict overall survival for select cancer types with focus on head and neck squamous cell carcinoma (HNSCC).Methods: Peripheral blood samples from 9,365 patients seen in a tertiary teaching hospital with nine different primary tumors were retrospectively examined. HNSCC RNA-sequencing data from The Cancer Genome Atlas were analyzed by two computational means [Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE)] to extend our observations to the tumor microenvironment.Results: For HNSCC, platelet count was more predictive of overall survival for males [log-rank test HR = 1.809; 95% confidence interval (CI), 1.461-2.239 vs. HR = 1.287; 95% CI, 0.8901-1.861], whereas NLR was more predictive for females (HR = 2.627; 95% CI, 1.716-4.02 vs. HR = 1.261; 95% CI, 0.998-1.593). For females, lymphocyte count was more associated with survival than neutrophil count (multivariate Cox regression P = 0.0015 vs. P = 0.7476). Both CIBERSORT (P = 0.0061) and ESTIMATE (P = 0.022) revealed greater immune infiltration in females. High tumor infiltration by T lymphocytes was more strikingly associated with survival in females (HR = 0.20, P = 0.0281) than in males (HR = 0.49, P = 0.0147).Conclusions: This is the first study to comprehensively demonstrate sex bias in the clinical utility of platelet, granulocyte, and lymphocyte counts as biomarkers to prognosticate HNSCC patients.Impact This work emphasizes the necessity to consider sex in appraising inflammatory markers for cancer risk stratification. Cancer Epidemiol Biomarkers Prev; 27(10); 1176-85. ©2018 AACR.