Prognostic impact and potential predictive role of baseline circulating tumor cells in locally advanced head and neck squamous cell carcinoma

•High detection rate of Circulating Tumor Cells (CTCs) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients with an isolation by size technique.•CTCs and Circulating Tumor Microemboli (CTM) have significant prognostic impact in LA-HNSCC.•CTCs counts are predictors of response to non-surgical treatment in LA-HNSCC.•High CTCs counts and presence of CTM are potential predictors of induction chemotherapy benefit in this population. The prognostic impact of circulating tumor cells (CTCs) or circulating tumor microemboli (CTM) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is yet to be determined, with conflicting results in previous trials. The role of induction chemotherapy (ICT) in the management of LA-HNSCC is controversial with no predictive biomarkers to guide treatment strategy in this scenario. The aim of this trial is to determine the prognostic impact of CTCs and CTM, their biomarkers expression by immunocytochemistry (ICC), and its potential role as predictors of ICT benefit in LA-HNSCC. Prospective study, with newly diagnosed stage III/IV non-metastatic LA-HNSCC patients treated with curative intent. Blood samples analyzed for CTCs and CTM before treatment using the ISET method. A total of 83 patients were included. CTCs counts were an independent prognostic factor for overall survival (OS; HR: 1.17; 95 %CI: 1.05–1.31; p = 0.005) and progression free survival (PFS; HR:1.14; 95 %CI: 1.03–1.26; p = 0.007). Using the Lausen and Schumacher technique, 2.8 CTCs/mL for OS and 3.8 CTCs/mL for PFS were defined as the best cut-offs. CTM were detected in 27.7% of patients, correlating with worse PFS (HR = 2.70; IC95%: 1.30–5.58; p = 0.007). MRP-7 expression in CTM correlated with worse OS (HR = 3.49; 95 %CI: 1.01–12.04; p = 0.047) and PFS (HR = 3.62; 95 %CI: 1.08–12.13; p = 0.037). CTCs counts were predictive of complete response to treatment (OR = 0.74; 95 %CI: 0.58–0.95; p = 0.022) and high counts (cut-off 3.8/mL) and CTM were potential predictors of ICT benefit. CTCs/CTM had significant prognostic impact and potential role as predictors of ICT benefit in LA-HNSCC.