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Surgical Impact on Circulating Tumor and Hybrid Cells in Head and Neck Cancer: A Pilot Study

Evgeniya S. Grigoryeva1,*, Anna Y. Kalinchuk1, Irina K. Fedorova2, Vladislav O. Tskhai2, Denis E. Kulbakin2, Liubov A. Tashireva1
1 The Laboratory of Molecular Therapy of Cancer, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
2 The Department of Head and Neck Cancer, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia
* Corresponding Author: Evgeniya S. Grigoryeva. Email: email
(This article belongs to the Special Issue: Discover Biomarkers for Personalized Oncology)

Oncology Research https://doi.org/10.32604/or.2026.076831

Received 27 November 2025; Accepted 15 April 2026; Published online 06 August 2026

Abstract

Objective: Surgery is known to significantly influence both the quantity and functional characteristics of circulating tumor cells (CTCs) in the bloodstream. Our cohort study aimed to characterize the landscape of CTCs and circulating hybrid cells (CHCs) in patients with head and neck cancer in peri-operative period. Methods: 26 patients were recruited and CTC and CHC counts were evaluated using four epithelial markers (EpCAM with differential localization of expression—membrane and intracellular, cytokeratin 7/8, and pan-cytokeratin) by flow cytometry. Expression of EpCAM and pan-cytokeratin in tumor tissue slides was assessed by multiplex immunofluorescence analysis. Results: The study revealed that CD45+ CHCs dominated the circulating landscape, outnumbering classical CD45 CTCs by over forty-fold. Both compartments exhibited phenotypic heterogeneity reflecting ongoing epithelial-to-mesenchymal transition. Surgical resection significantly depleted specific CD45+ CHC subpopulations but had no effect on CD45 CTCs. Postoperative CHC counts above 2.5 cells/mL were associated with favorable outcomes, whereas depletion below this threshold predicted poor clinical outcomes and relapse. Although the patient cohort was limited, robust statistical analyses validate the significance of our observations. Conclusion: Our findings identify a novel informative marker for predicting head and neck cancer progression, which may serve as part of a non-invasive liquid biopsy.

Keywords

Circulating tumor cells; surgical intervention; head and neck cancer; recurrence-free survival
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