Objective: The aim of this study was to investigate the presence of circulating tumor cells (CTCs) and their correlation with prognostic factors and clinical outcomes in treatment-naive patients with oral squamous cell carcinoma.

Study design: CTCs were isolated using the OncoDiscover technique from presurgically obtained peripheral blood of 152 patients with treatment-naive oral squamous cell carcinoma. Sensitivity analysis was performed by including 40 healthy controls. CTC cutoff values for clinicopathologic factors were obtained from receiver operating characteristic curves. Multivariate models determined the significance of CTCs as independent variables. Kaplan–Meier analysis differentiated overall survival based on CTC values corresponding to disease stage.

Results: Sensitivity, specificity, and accuracy of CTC detection were 94.32%, 98%, and 95.17%, respectively. The platform differentiated true positives at >3.5 CTCs (P < .00001). CTC counts above 20.5 were suggestive of nodal metastasis (P < .0001), with a linear trend for detecting occult metastasis (P = .061). Early and advanced stages could be differentiated by >13.5 CTCs (P < .0001). Elevated CTC levels were significantly associated with extranodal extension (>21.45 CTCs, P = .025), perineural invasion (>19.35 CTCs, P = .049), and depth of invasion (>12.5 CTCs, P = .0038). Median survival was reduced by 19 months when CTC levels were >13.

Conclusions: Preoperative CTC levels demonstrated a strong correlation with adverse clinicopathologic factors and suggested their role as a sensitive prognostic marker for predicting survival outcomes and disease progression. (Oral Surg Oral Med Oral Pathol Oral Radiol 2022;134:73–83)