Elective Neck Dissection in Stage I and II Sinonasal Squamous Cell Carcinomas : A European Head and Neck Cancer Center Survey Study

The knowledge about the molecular alterations which are found in head and neck squamous cell carcinomas (HNSCC) has much increased in recent years. However, we are still awaiting the translation of this knowledge to new diagnostic and therapeutic options. Among the many molecular changes that are detected in head and neck cancer, the abnormalities in several signaling pathways, which regulate cell proliferation, cell death and stemness, seem to be especially promising with regard to the development of targeted therapies. Canonical Wnt signaling is a pathway engaged in the formation of head and neck tissues, however it is not active in adult somatic mucosal cells. The aim of this review paper is to bring together significant data related to the current knowledge on the mechanisms and functional significance of the dysregulation of the Wnt/β-catenin pathway in head and neck tumors. Research evidence related to the role of Wnt signaling activation in the stimulation of cell proliferation, migration and inhibition of apoptosis in HNSCC is presented. Moreover, its role in promoting stemness traits in head and neck cancer stem-like cells is described. Evidence corroborating the hypothesis that the Wnt signaling pathway is a very promising target of novel therapeutic interventions in HNSCC is also discussed.

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Who merits a neck dissection after definitive chemoradiotherapy for N2-N3 squamous cell head and neck cancer?

Head & Neck ◽

10.1002/hed.10293 ◽

2003 ◽

Vol 25 (10) ◽

pp. 791-798 ◽

Cited By ~ 135

Author(s):

Scott A. McHam ◽

David J. Adelstein ◽

Lisa A. Rybicki ◽

Pierre Lavertu ◽

Ramon M. Esclamado ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Dissection ◽

Neck Cancer ◽

Squamous Cell ◽

Definitive Chemoradiotherapy

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

Blood ◽

10.1182/blood.v104.11.2908.2908 ◽

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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Neck dissection following organ preservation protocols prolongs feeding tube dependence in patients with advanced head and neck cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.5525 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 5525-5525

Author(s):

M. Lango ◽

K. Ende ◽

S. Ahmad ◽

S. J. Feigenberg ◽

J. A. Ridge

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Dissection ◽

Neck Cancer ◽

Organ Preservation ◽

Squamous Carcinoma ◽

Feeding Tube ◽

Independent Effect ◽

Cancer Center ◽

Surgical Specimen

5525 Background: Organ preserving strategies employed in the treatment of advanced stage head and neck cancer frequently result in significant organ dysfunction including dysphagia and feeding tube dependence. While the acute and chronic effects of radiation and chemotherapy are known to contribute to swallowing impairment, the effect of a neck dissection, performed 6–8 weeks following the completion of treatment is unknown. Methods: Retrospective review of Stage III/IV squamous carcinoma patients treated with primary radiation with/without chemotherapy and a post-treatment neck dissection, who remain free of locoregional or distant failure for a minimum of two years. Predictors of prolonged feeding tube dependence (>24 months following the completion of treatment) were evaluated using univariate and multivariate analysis. To determine the independent effect of neck dissection on length of feeding tube dependence, patients matched for covariates were also compared. Results: 79 patients treated at the Fox Chase Cancer Center between 1992 to 2003 were included in this study. 61 (77.2%) received chemotherapy and 37 (46.8%) underwent a neck dissection. The surgical specimen was positive for residual carcinoma in 12 patients (33%). 57 patients (71.3%) underwent placement of a feeding tube. The median time to removal of feeding tubes was 12 months [7–17 months, 95% CI]. Feeding tube-free status at 24 months was associated with use of standard radiotherapy (p = 0.031), N0 vs N+ neck stage (p = 0.041) and management without a neck dissection (p = 0.003). There was no association with age, T-stage, tumor site or use of chemotherapy. On multiple regression, only neck dissection remained a predictor of retained feeding tube at 24 months (p = 0.013). In patients matched for N-stage and treatment selection, those who underwent a neck dissections required a feeding tube a median of 36 months compared with 10 months for those without a neck dissection [32–57 months versus 7–13 months, 95% CI, p = 0.021]. The two year frequency of feeding tube dependence was 14/34 (41%) versus 3/30 (10%), respectively (p = 0.005). Conclusions: Neck dissection may contribute dysphagia experienced by head and neck cancer patients treated with organ preservation protocols. No significant financial relationships to disclose.

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P-167 Comparison of Clinical and Pathological Staging in Patients with Head and Neck Cancer After Elective Neck Dissection

Oral Oncology ◽

10.1016/s1368-8375(21)00453-x ◽

2021 ◽

Vol 118 ◽

pp. 19

Author(s):

João Viana Pinto ◽

Mafalda Martins Sousa ◽

Helena Silveira ◽

Fernando Vales ◽

Carla Pinto Moura

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Dissection ◽

Neck Cancer ◽

Elective Neck Dissection ◽

Pathological Staging

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Modified radical neck dissection and postoperative radiotherapy in squamous cell head and neck cancer

The American Journal of Surgery ◽

10.1016/0002-9610(85)90160-6 ◽

1985 ◽

Vol 150 (4) ◽

pp. 488-490 ◽

Cited By ~ 6

Author(s):

Nathan W. Pearlman ◽

F.Bing Johnson ◽

Ralph C. Kennaugh

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Dissection ◽

Neck Cancer ◽

Squamous Cell ◽

Postoperative Radiotherapy ◽

Radical Neck Dissection ◽

Modified Radical Neck Dissection

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An Infection-Based Murine Model for Papillomavirus-Associated Head and Neck Cancer

mBio ◽

10.1128/mbio.00908-20 ◽

2020 ◽

Vol 11 (3) ◽

Author(s):

Tao Wei ◽

Darya Buehler ◽

Ella Ward-Shaw ◽

Paul F. Lambert

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Cancer ◽

Squamous Cell ◽

Squamous Cell Carcinomas ◽

Preclinical Model ◽

Invasive Squamous Cell Carcinoma ◽

Papillomavirus Infection ◽

Neck Disease

ABSTRACT Human papillomavirus (HPV) is the most common sexually transmitted pathogen, and high-risk HPVs contribute to 5% of human cancers, including 25% of head and neck squamous cell carcinomas (HNSCCs). Despite the significant role played by HPVs in HNSCC, there is currently no available in vivo system to model the process from papillomavirus infection to virus-induced HNSCC. In this paper, we describe an infection-based HNSCC model, utilizing a mouse papillomavirus (MmuPV1), which naturally infects laboratory mice. Infections of the tongue epithelium of two immunodeficient strains with MmuPV1 caused high-grade squamous dysplasia with early signs of invasive carcinoma over the course of 4 months. When combined with the oral carcinogen 4-nitroquinoline-1-oxide (4NQO), MmuPV1 caused invasive squamous cell carcinoma (SCC) on the tongue of both immunodeficient and immunocompetent mice. These tumors expressed markers of papillomavirus infection and HPV-associated carcinogenesis. This novel preclinical model provides a valuable new means to study how natural papillomavirus infections contribute to HNSCC. IMPORTANCE The species specificity of papillomavirus has limited the development of an infection-based animal model to study HPV-associated head and neck carcinogenesis. Our study presents a novel in vivo model using the mouse papillomavirus MmuPV1 to study papillomavirus-associated head and neck cancer. In our model, MmuPV1 infects and causes lesions in both immunodeficient and genetically immunocompetent strains of mice. These virally induced lesions carry features associated with both HPV infections and HPV-associated carcinogenesis. Combined with previously identified cancer cofactors, MmuPV1 causes invasive squamous cell carcinomas in mice. This model provides opportunities for basic and translational studies of papillomavirus infection-based head and neck disease.

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Elective Neck Dissection in Head and Neck Cancer

Archives of Otolaryngology - Head and Neck Surgery ◽

10.1001/archotol.1968.00760060473006 ◽

1968 ◽

Vol 87 (5) ◽

pp. 471-476 ◽

Cited By ~ 8

Author(s):

E. M. Skolnik ◽

L. T. Tenta ◽

M. E. Tardy ◽

D. M. Wineinger

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Neck Dissection ◽

Neck Cancer ◽

Elective Neck Dissection

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Head and Neck Cancer Stem Cells

Journal of Dental Research ◽

10.1177/0022034511423393 ◽

2011 ◽

Vol 91 (4) ◽

pp. 334-340 ◽

Cited By ~ 47

Author(s):

S. Krishnamurthy ◽

J.E. Nör

Keyword(s):

Stem Cells ◽

Head And Neck Cancer ◽

Cancer Stem Cells ◽

Head And Neck ◽

Neck Cancer ◽

Squamous Cell ◽

Squamous Cell Carcinomas ◽

Self Renewal ◽

Perivascular Niche

Most cancers contain a small sub-population of cells that are endowed with self-renewal, multipotency, and a unique potential for tumor initiation. These properties are considered hallmarks of cancer stem cells. Here, we provide an overview of the field of cancer stem cells with a focus on head and neck cancers. Cancer stem cells are located in the invasive fronts of head and neck squamous cell carcinomas (HNSCC) close to blood vessels (perivascular niche). Endothelial cell-initiated signaling events are critical for the survival and self-renewal of these stem cells. Markers such as aldehyde dehydrogenase (ALDH), CD133, and CD44 have been successfully used to identify highly tumorigenic cancer stem cells in HNSCC. This review briefly describes the orosphere assay, a method for in vitro culture of undifferentiated head and neck cancer stem cells under low attachment conditions. Notably, recent evidence suggests that cancer stem cells are exquisitely resistant to conventional therapy and are the “drivers” of local recurrence and metastatic spread. The emerging understanding of the role of cancer stem cells in the pathobiology of head and neck squamous cell carcinomas might have a profound impact on the treatment paradigms for this malignancy.

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