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Petar Suton, Marko Skelin, Zoran Rakusic, Stjepan Dokuzovic, Ivica Luksic
PURPOSE: Human papilloma virus (HPV)-associated oropharyngeal cancer (OPC) is a special entity among head and neck squamous cell carcinomas (HNSCCs). Given its favorable prognosis, one of the de-escalating strategies in the treatment of OPC includes the introduction of cetuximab (C225) instead of cisplatin (CDDP) in conjunction with radiotherapy. An updated meta-analysis of published studies has been performed, which directly compared the efficacy of CDDP vs. C225 given concurrently with radiotherapy as definitive treatment of p16-positive OPC...
March 18, 2019: European Archives of Oto-rhino-laryngology
Stina Syrjänen, Kari Syrjänen
BACKGROUND: The association of human papillomavirus (HPV) with head and neck squamous cell carcinoma (HNSCC) was first described in 1982-1983 by the authors of this review. Prompted by this discovery 35 years ago, an entirely new field of HPV research has emerged, resulting in a paradigm shift from smoking and alcohol as the only etiological factors to confirmation of HNSCC as an important group of HPV-related human malignancies. SUMMARY: In this review, the authors first describe the scope (i...
March 12, 2019: Acta Cytologica
Jay Friedman, Michelle Padget, John Lee, Jeffrey Schlom, James Hodge, Clint Allen
High affinity natural killer cells (haNKs) are a cell therapy product capable of mediating both direct and antibody-dependent cell-mediated cytotoxicity (ADCC). These cells may be particularly useful in tumors that escape T-cell anti-tumor immunity by harboring antigen processing and presentation defects. Here, we demonstrated that haNKs directly kill both HPV-positive and negative head and neck squamous cell carcinoma cells. Variable tumor cell sensitivity to haNK direct cytotoxicity did not correlated with MHC class I chain-related protein A or B (MICA or MICB) expression...
March 2019: Oral Oncology
Yuguang Zhao, Wenhui Liu, Meiting Sun, Qiuli Miao, Yingmin Liu, Huimin Tian, Yapin Su, Fujun Han
BACKGROUND: We conducted a meta-analysis to examine the associations of age, human papillomavirus (HPV) infection, and performance status with the overall survival (OS) benefits of patients with head and neck squamous cell carcinoma (HNSCC) after treatment with versus without epidermal growth factor receptor (EGFR) inhibitors. METHODS: We systematically searched literature for randomized controlled trials comparing chemotherapy or radiotherapy with versus without EGFR inhibitors in locoregionally advanced, recurrent, or metastatic HNSCCs...
March 2019: Critical Reviews in Oncology/hematology
Sayuri Miyauchi, Sangwoo S Kim, John Pang, Kathryn Ann Gold, J Silvio Gutkind, Joseph Califano, Loren K Mell, Ezra E W Cohen, Andrew B Sharabi
Head and neck squamous cell carcinoma (HNSCC) accounts for more than 600,000 cases and 380,000 deaths annually worldwide. While human papilloma virus (HPV)-associated HNSCCs have better overall survival compared to HPV-negative HNSCC, loco-regional recurrence remains a significant cause of mortality and additional combinatorial strategies are needed to improve outcomes. The primary conventional therapies to treat HNSCC are surgery, radiation, and chemotherapies; however multiple other targeted systemic options are used and being tested including cetuximab, bevacizumab, mTOR inhibitors, and metformin...
February 27, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Jie-Gang Yang, Wei-Ming Wang, Hou-Fu Xia, Zi-Li Yu, Hui-Min Li, Jian-Gang Ren, Gang Chen, Bei-Ke Wang, Jun Jia, Wei Zhang, Yi-Fang Zhao
Tumor angiogenesis is critical for tumor progression as the new blood vessels supply nutrients and facilitate metastasis. Previous studies indicate tumor associated lymphocytes, including B cells and T cells, contribute to tumor angiogenesis and tumor progression. The present study aims to identify the function of Lymphotoxin-α (LT-α), which is secreted by the activated lymphocytes, in the tumor angiogenesis of head and neck squamous cell carcinoma (HNSCC). The co-culture system between HNSCC cell line Cal27 and primary lymphocytes revealed that tumor cells promoted the LT-α secretion in the co-cultured lymphocytes...
February 20, 2019: International Journal of Cancer. Journal International du Cancer
Daniel Dejaco, Teresa Steinbichler, Volker Hans Schartinger, Natalie Fischer, Maria Anegg, Joszef Dudas, Andrea Posch, Gerlig Widmann, Herbert Riechelmann
OBJECTIVE: To provide data on specific growth rates (SGRs) of primary tumours (PT-SGR) and largest pathological cervical lymph nodes (LN-SGR) for head and neck squamous cell carcinoma (HNSCC). To explore PT-SGR's and LN-SGR's correlation with selected biomarkers epidermal growth factor receptor (EGFR), Ki67 and CD44. DESIGN AND SETTING: Retrospective study performed at a tertiary oncological referral centre in Innsbruck, Austria. PARTICIPANTS: Adult patients with incident HNSCC treated with primary radiotherapy (RT) or radiochemotherapy (RCT)...
February 19, 2019: BMJ Open
Jesse J McClure, Viswanathan Palanisamy
The RNA-binding protein fragile-X mental retardation autosomal 1 (FXR1) is upregulated in head and neck squamous cell carcinomas (HNSCCs) and expressed as at least seven isoforms in humans. Only two of these isoforms are capable of binding to RNA containing G-quadruplex structures. We suggest that these unique isoforms play a role in the pathogenesis of HNSCC.
February 2019: Trends in Cancer
Nicholas C J Lee, Jacqueline R Kelly, Yi An, Henry S Park, Benjamin L Judson, Barbara A Burtness, Zain A Husain
BACKGROUND: Treatment at high-volume surgical facilities (HVSFs) provides a survival benefit for patients with head and neck squamous cell carcinomas (HNSCCs); however, it is unknown what role postoperative radiation therapy (PORT) plays in achieving the improved outcomes. METHODS: From the National Cancer Database, 6844 patients with locally advanced invasive HNSCCs of the oral cavity, oropharynx, larynx, and hypopharynx who underwent definitive surgery with PORT between 2004 and 2013 were identified...
February 12, 2019: Cancer
Vladimir Avkshtol, Elizabeth A Handorf, John A Ridge, Brooke K Leachman, Jeffrey C Liu, Jessica Bauman, Thomas J Galloway
BACKGROUND: Compare adjuvant radiation dose trends and outcomes in head and neck squamous cell carcinoma (HNSCC). METHODS: Nonmetastatic HNSCCs treated between 2004 and 2014 with primary site surgery, lymph node dissection, and adjuvant radiation were identified in the National Cancer Database. Standard dose radiation (SD-RT) was defined as an equivalent dose in 2 Gy (EQD2) ≥56.64 and ≤60 Gy and high-dose radiation (HD-RT) as an EQD2 >60 and <70 Gy...
February 9, 2019: Head & Neck
Takeharu Kanazawa, Kiyoshi Misawa, Kazuya Shinmura, Yuki Misawa, Gen Kusaka, Mikiko Maruta, Toru Sasaki, Yusuke Watanabe, Thomas E Carey
While remarkable progress has been made in standard treatments for head and neck squamous cell carcinomas (HNSCCs), the long-term survival remains at an unsatisfactory 40-50%. To improve the survival rate, biomarkers for optimal treatment selection and prognostic prediction, as well as novel, low-toxicity treatment strategies, are required. Galanin receptor (GALR) 1 and GALR2 are well-studied tumor suppressors in HNSCCs. Compared with other clinicopathological factors, the epigenetic variants of GALRs have been found to be the most powerful markers to predict the prognosis of HNSCC patients...
January 14, 2019: Expert Review of Molecular Diagnostics
Musaffe Tuna, Christopher I Amos, Gordon B Mills
Smoking and alcohol intake are major risk factors in head and neck squamous cell carcinomas (HNSCCs). Although the link between TP53 mutation and smoking has been well established, very little is known about the link between acquired uniparental disomy (aUPD) and smoking and/or alcohol consumption or other clinical characteristics. We used TCGA genomic data to investigate whether smoking, alcohol intake, clinical and demographic variables, HPV status and TP53 mutation are associated with aUPD at specific chromosomal regions...
January 4, 2019: Neoplasia: An International Journal for Oncology Research
Atlas Khan, Qian Liu, Xuelian Chen, Andres Stucky, Parish P Sedghizadeh, Daniel Adelpour, Xi Zhang, Kai Wang, Jiang F Zhong
Next generation sequencing (NGS) provides an opportunity to detect viral species from RNA-seq data of human tissues, but existing computational approaches do not perform optimally on clinical samples. We developed a bioinformatics method called VirTect for detecting viruses in neoplastic human tissues using RNA-seq data. Here, we used VirTect to analyze RNA-seq data from 363 HNSCC (head and neck squamous cell carcinoma) patients and identified 22 human papillomavirus (HPV)-induced HNSCCs. These predictions were validated by manual review of pathology reports on histopathologic specimens...
December 30, 2018: Molecular Oncology
Valentina Frezza, Claudia Fierro, Elena Gatti, Angelo Peschiaroli, Anna Maria Lena, Margherita Annicchiarico Petruzzelli, Eleonora Candi, Lucia Anemona, Alessandro Mauriello, Pier Giuseppe Pelicci, Gerry Melino, Francesca Bernassola
Accumulating evidence has proved that deregulation of ΔNp63 expression plays an oncogenic role in head and neck squamous cell carcinomas (HNSCCs). Besides p63, the type 1-insulin-like growth factor (IGF) signalling pathway has been implicated in HNSCC development and progression. Most insulin/IGF1 signalling converges intracellularly onto the protein adaptor insulin receptor substrate-1 (IRS-1) that transmits signals from the receptor to downstream effectors, including the PI3K/AKT and the MAPK kinase pathways, which, ultimately, promote proliferation, invasion, and cell survival...
December 28, 2018: Aging
Ariel L Hernandez, Ying Wang, Hilary L Somerset, Stephen B Keysar, Dara L Aisner, Carrie Marshall, Daniel W Bowles, Sana D Karam, David Raben, Antonio Jimeno, Marileila Varella-Garcia, Xiao-Jing Wang
Reports regarding the frequency of SMAD4 loss in human head and neck squamous cell carcinoma (HNSCC) vary significantly. We have shown that SMAD4 deletion contributes to HNSCC initiation and progression. Therefore, accurately detecting genetic SMAD4 loss is critical to determine prognosis and therapeutic interventions in personalized medicine. We developed a SMAD4 fluorescence in situ hybridization (FISH) assay to identify chromosomal SMAD4 loss at the single cell level of primary HNSCC specimens and patient derived xenograft (PDX) tumors derived from HNSCCs...
December 21, 2018: Molecular Carcinogenesis
Lei Huang, Odile David, Robert J Cabay, Klara Valyi-Nagy, Virgilia Macias, Rong Zhong, Barry Wenig, Lawrence Feldman, Ralph Weichselbaum, Michael T Spiotto
Purpose: In advanced stage head and neck squamous cell cancers (HNSCC), approximately half of the patients with lymph node metastases (LNM) are not cured. Given the heterogeneous outcomes in these patients, we profiled the expression patterns of LNMs to identify the biological factors associated with patient outcomes. Experimental Design: We performed mRNAseq and miRNAseq on 72 LNMs and 29 matched primary tumors from 34 patients with HNSCC. Clustering identified molecular subtypes in LNMs and in primary tumors...
December 20, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Steve Seltzsam, Frank Ziemann, Kristin Dreffke, Stefanie Preising, Andrea Arenz, Ulrike Schötz, Rita Engenhart-Cabillic, Ekkehard Dikomey, Andrea Wittig
Human papillomavirus (HPV) associated squamous cell carcinomas of the head and neck region (HPV+ HNSCCs) harbor diverging biological features as compared to classical noxa-induced (HPV-) HNSCC. One striking difference between subtypes is that the tumor suppressor gene TP53 is usually not mutated in HPV+ HNSCCs. However, p53 is inhibited by viral oncoprotein E6, leading to premature proteasomal degradation. We asked whether bortezomib (BZM), a clinically approved inhibitor of the proteasome, can functionally restore p53 and investigated in how far this will result in an enhanced radio- or chemosensitivity of HPV+ HNSCC cell lines...
December 13, 2018: Translational Oncology
Hyang Joo Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
BACKGROUND: The purpose of this study was to comprehensively characterize head and neck squamous cell carcinoma (HNSCC) arising in young patients (<45 years old). METHODS: We performed immunohistochemistry, silver, and fluorescence in situ hybridization using samples obtained from 396 radically resected cases among 1787 HNSCCs. RESULTS: Young age HNSCCs occurred in 10.9% (194/1787) and were most common in the oral tongue (50.5%). They revealed distinctively lower frequency of p16 positivity, high c-MET expression, MET copy number gain, and lower pan-Trk expression...
December 10, 2018: Head & Neck
Kara M Ruicci, Jalna Meens, Ren X Sun, Giananthony Rizzo, Nicole Pinto, John Yoo, Kevin Fung, Danielle MacNeil, Joe S Mymryk, John W Barrett, Paul C Boutros, Laurie Ailles, Anthony C Nichols
Head and neck squamous cell carcinomas (HNSCCs) frequently harbor alterations in the PI3K/AKT/mTOR signalling axis, particularly in the PIK3CA gene. PI3K-targeted agents have therefore gained considerable preclinical and clinical interest as emerging therapies for HNSCC. Identification of predictive biomarkers of response would advance the clinical application of PI3K-targeted drugs for patients in order to achieve maximal benefit. To date, studies of drug biomarkers have largely focused on screening cell lines, with much more limited in vivo testing, usually only as validation...
November 23, 2018: International Journal of Cancer. Journal International du Cancer
Francesco Broccolo, Giulia Ciccarese, Agostino Rossi, Luca Anselmi, Francesco Drago, Antonio Toniolo
Background: Oral and oropharyngeal squamous cell carcinomas (OSCC and OPSCC) represent the majority of head and neck squamous cell carcinomas (HNSCC). Human papillomavirus (HPV) is an important etiologic factor together with Epstein-Barr virus (EBV). Little is known on the prevalence of major herpesviruses [EBV, cytomegalovirus (CMV) and HHV-6, - 7 and - 8] in HNSCCs. Methods: Fifty-one formalin-fixed paraffin-embedded (FFPE) tissue samples taken at surgery (40 oropharyngeal, 11 oral) were analyzed for 40 HPV genotypes (20 high-risk types), EBV, CMV, HHV-6, - 7 and - 8 by quantitative PCR...
2018: Infectious Agents and Cancer
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