scholarly journals Circulating p16-Positive and p16-Negative Tumor Cells Serve as Independent Prognostic Indicators of Survival in Patients with Head and Neck Squamous Cell Carcinomas

2021 ◽  
Vol 11 (11) ◽  
pp. 1156
Author(s):  
Pei-Hung Chang ◽  
Hung-Ming Wang ◽  
Yung-Chia Kuo ◽  
Li-Yu Lee ◽  
Chia-Jung Liao ◽  
...  
Keyword(s):  
Head And Neck ◽  
Tumor Cells ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Final Analysis ◽  
Squamous Cell Carcinomas ◽  
Prognostic Indicators ◽  
Cell Counts ◽  
P16 Expression

Background: Decisions regarding the staging, prognosis, and treatment of patients with head and neck squamous cell carcinomas (HNSCCs) are made after determining their p16 expression levels and human papillomavirus (HPV) infection status. Methods: We investigated the prognostic roles of p16-positive and p16-negative circulating tumor cells (CTCs) and their cell counts in HNSCC patients. We enrolled patients with locally advanced HNSCCs who received definitive concurrent chemoradiotherapy for final analysis. We performed CTC testing and p16 expression analysis before chemoradiotherapy. We analyzed the correlation between p16-positive and p16-negative CTCs and HPV genotyping, tissue p16 expression status, response to chemoradiotherapy, disease-free survival, and overall survival. Results: Forty-one patients who fulfilled the study criteria were prospectively enrolled for final analysis. The detection rates of p16-positive (>0 cells/mL blood) and p16-negative (≥3 cells/mL blood) CTCs were 51.2% (n = 21/41) and 70.7%, respectively. The best responses of chemoradiotherapy and the p16 positivity of CTCs are independent prognostic factors of disease progression, with hazard ratios of 1.738 (95% confidence interval (CI): 1.031–2.927), 5.497 (95% CI: 1.818–16.615), and 0.176 (95% CI: 0.056–0.554), respectively. The p16 positivity of CTCs was a prognostic factor for cancer death, with a hazard ratio of 0.294 (95% CI: 0.102–0.852). Conclusions: The p16-positive and p16-negative CTCs could predict outcomes in HNSCC patients receiving definitive chemoradiotherapy. This non-invasive CTC test could help stratify the risk and prognosis before chemoradiotherapy in clinical practice and enable us to perform de-intensifying therapies.

Radiochemotherapy in Locally Advanced Squamous Cell Carcinomas of the Head and Neck

2009 ◽  
Vol 21 (7) ◽  
pp. 525-531 ◽  
Author(s):  
O. Matzinger ◽  
A. Zouhair ◽  
R.O. Mirimanoff ◽  
M. Ozsahin
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Squamous Cell Carcinomas

Predictors of response and survival after concurrent chemotherapy and radiation for locally advanced squamous cell carcinomas of the head and neck

Cancer ◽  
2001 ◽  
Vol 91 (3) ◽  
pp. 548-554 ◽  
Author(s):  
Mohan Suntharalingam ◽  
Michael L. Haas ◽  
David A. Van Echo ◽  
Robert Haddad ◽  
Maria C. Jacobs ◽  
...  
Keyword(s):  
Head And Neck ◽  
Squamous Cell ◽  
Locally Advanced ◽  
Concurrent Chemotherapy ◽  
Squamous Cell Carcinomas ◽  
Predictors Of Response

Expression of Erythropoietin and Erythropoietin Receptor in Squamous Cell Carcinomas of the Head and Neck: Levels of Erythropoietin Expression Correlate with Tumor Hypoxia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2908-2908
Author(s):  
Murat O. Arcasoy ◽  
Khalid Amin ◽  
Shu-Chuan Chou ◽  
Zishan A. Haroon ◽  
Mahesh Varia ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Head And Neck Cancer ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Tumor Cells ◽  
Neck Cancer ◽  
Squamous Cell ◽  
Tumor Hypoxia ◽  
Squamous Cell Carcinomas ◽  
Glycoprotein Hormone

Abstract Erythropoietin (EPO), an oxygen-regulated glycoprotein hormone, is a hematopoietic cytokine that stimulates erythropoiesis by binding to its cellular receptor EPOR. The recombinant form of human EPO is widely used in clinical practice for the prevention or treatment of anemia associated with cancer and chemo-radiation therapy. However, in a recent randomized, placebo-controlled trial involving patients receiving curative radiotherapy for squamous cell carcinoma of the head and neck, EPO treatment was associated with poorer loco-regional progression-free survival. The purpose of this study was to determine whether EPOR and its ligand EPO are expressed in primary squamous cell carcinomas of the head and neck. We also investigated the hypothesis that EPO expression in malignant cells may be associated with the presence of tumor hypoxia, an important factor involved in resistance to radiation treatment, tumor aggressiveness and poor prognosis. Twenty-one patients with squamous cell carcinoma of the head and neck were enrolled in a tumor hypoxia study under a research protocol approved by the Institutional Review Board at the University of North Carolina Hospitals. All patients provided signed informed consent. The patients received an intravenous infusion of the hypoxia marker pimonidazole hydrochloride (Hypoxyprobe-1™) prior to multiple tumor biopsies. Two or more biopsies were available from all except one primary tumor. The tissue specimen from one patient with laryngeal carcinoma was excluded because of availability of only a single, small and fragmented biopsy. Contiguous sections from 74 biopsies were analyzed by immunohistochemistry for expression of EPOR and EPO as well as pimonidazole binding. We found EPOR expression in tumor cells in 97% of the biopsies. The pattern of EPOR immunoreactivity was predominantly cytoplasmic but was found to be localized to the membrane in some sections. Co-expression of EPO was observed in 90% of biopsies. Qualitative and semi-quantitative analyes for EPO staining and tumor hypoxia on a section-by-section basis revealed that EPO and pimonidazole adduct staining did not always co-localize within tumors but there was a significant positive correlation between levels of micro-regional EPO expression and pimonidazole binding (r = 0.736, P < 0.001, n=20 by two-tailed Spearman’s rank correlation analysis). These data demonstrate the co-expression of EPOR and its ligand EPO in squamous carcinoma cells suggesting that EPO may play a novel role as a potential autocrine or paracrine growth factor in head and neck cancer. Furthermore, EPO expression in tumor cells may be modulated, at least in part, by tumor hypoxia. The expression of EPOR needs to be taken into consideration in the design of future clinical trials investigating the role of recombinant human EPO in head and neck cancer.

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