Squamous cell carcinoma of the tongue (TSCC) has one of the poorest prognoses of head and neck cancers. This study aims to improve early detection of the disease by identifying salivary biomarkers that can identify a spectrum of patients progressing from high-risk to
TSCC. We also examine the mortality of exophytic and endophytic TSCC, expecting the elevated cytokine levels in endophytic patients to be associated with a shorter survival. Saliva was collected from patients with TSCC and controls and cytokine protein levels were measured. Specimens were collected from the Los Angeles County (LAC) + University of Southern California (USC) and USC University Hospital clinics. A convenience sample of patients with TSCC was divided into endophytic (n = 10) and exophytic (n = 8) cancer by physician diagnosis. Controls were divided into 4 groups of 14 based on their high-risk smoking and drinking behaviors. Main outcome measures: The levels of IL-1a, IL-6, IL-8, VEGF-a and TNF-a in saliva were measured using quantitative ELISA and compared using two-way ANOVA. All five cytokines were elevated in the endophytic TSCC group compared to other groups, which correlated with the decreased survival rate (10.4 months) in this group compared to exophytic TSCC (24 months). IL-1a, IL-6, TNF-a and VEGF were also elevated in the exophytic TSCC group compared to smoking-drinking controls. Salivary levels of IL-1a, IL-6, IL-8, VEGF-a and TNF-a can identify the progression of TSCC from high-risk to neoplasm, serving as potential biomarkers for cancer screening and early detection. The correlation with survival implies a prognostic benefit and could serve as a tool for management decisions and future treatment targets.