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https://www.readbyqxmd.com/read/28526718/p16-hpv-and-cetuximab-what-is-the-evidence
#1
James A Bonner, Ricard Mesia, Jordi Giralt, Amanda Psyrri, Ulrich Keilholz, David I Rosenthal, Frank Beier, Jeltje Schulten, Jan B Vermorken
Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer worldwide. It has recently been appreciated that human papillomavirus (HPV) status (or p16 status, which is a frequently used surrogate for HPV status) is prognostic for oropharyngeal SCCHN. Here, we review and contextualize existing p16 and HPV data, focusing on the cetuximab registration trials in previously untreated, locoregionally advanced, nonmetastatic SCCHN (LA SCCHN) and in recurrent and/or metastatic SCCHN (R/M SCCHN): the IMCL-9815 and EXTREME clinical trials, respectively...
May 18, 2017: Oncologist
https://www.readbyqxmd.com/read/28525363/targeted-sequencing-of-tonsillar-and-base-of-tongue-cancer-and-human-papillomavirus-positive-unknown-primary-of-the-head-and-neck-reveals-prognostic-effects-of-mutated-fgfr3
#2
Cinzia Bersani, Lars Sivars, Linnea Haeggblom, Sebastian DiLorenzo, Michael Mints, Andreas Ährlund-Richter, Nikolaos Tertipis, Eva Munck-Wikland, Anders Näsman, Torbjörn Ramqvist, Tina Dalianis
BACKGROUND: Human papillomavirus positive (HPV+) tonsillar cancer (TSCC), base of tongue cancer (BOTSCC) and unknown primary cancer of the head and neck (HNCUP) have better outcome than corresponding HPV- cancers. To find predictive markers for response to treatment, and correlations and differences in mutated oncogenes and suppressor genes between HPV+ TSCC/BOTSSCC and HPV+ HNCUP and HPV- TSCC/BOTSCC targeted next-generation sequencing was performed of frequently mutated regions in 50 cancer related genes...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28522603/smad4-loss-is-associated-with-cetuximab-resistance-and-induction-of-mapk-jnk-activation-in-head-and-neck-cancer-cells
#3
Hiroyuki Ozawa, Ruchira Ranaweera, Evgeny Izumchenko, Eugene Makarev, Alex Zhavoronkov, Elana J Fertig, Jason D Howard, Ana Markovic, Atul Bedi, Rajani Ravi, Jimena Perez, Quynh-Thu Le, Christina S Kong, Richard C K Jordan, Hao Wang, Hyunseok Kang, Harry Quon, David Sidransky, Christine H Chung
Purpose: We previously demonstrated an association between decreased SMAD4 expression and cetuximab resistance in head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to further elucidate the clinical relevance of SMAD4 loss in HNSCC. Experimental Design: SMAD4 expression was assessed by immunohistochemistry in 130 newly diagnosed and 43 recurrent HNSCC patients. Correlative statistical analysis with clinicopathological data was also performed. OncoFinder, a bioinformatics tool, was used to analyze molecular signaling in TCGA tumors with low or high SMAD4 mRNA levels...
May 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28522585/herpes-simplex-virus-glycoprotein-d-targets-a-specific-dendritic-cell-subset-and-improves-the-performance-of-vaccines-to-human-papillomavirus-associated-tumors
#4
Bruna F M M Porchia, Ana Carolina R Moreno, Rodrigo N Ramos, Mariana O Diniz, Laís Helena T M de Andrade, Daniela S Rosa, José Alexandre M Barbuto, Silvia B Boscardin, Luís Carlos S Ferreira
Cervical cancer is a major public health problem and one of the leading causes of cancer deaths in women. Virtually all cases of cervical cancer, as well as a growing share of anal and head/neck tumors, are associated with human papillomavirus (HPV) infection. Despite the effectiveness, the available prophylactic vaccines do not benefit women with cervical lesions or cancer. Therefore, the search of new immunotherapeutic approaches to treat HPV-induced tumors is still a priority. The present study characterizes a therapeutic antitumor vaccine based on the genetic fusion of the Herpes simplex virus-1 (HSV-1) glycoprotein D (gD) with the E7 oncoprotein from HPV-16 (gDE7)...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28521433/effect-of-selective-small-molecule-inhibitors-on-mmp-9-and-vegfr-1-expression-in-p16-positive-and-negative-squamous-cell-carcinoma
#5
Benedikt Kramer, Johannes David Schultz, Clemens Hock, Alexander Sauter, Boris A Stuck, Karl Hörmann, Richard Birk, Christoph Aderhold
The identification of molecular targets in the therapy of human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is a primary aim of cancer research. Matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor receptor (VEGFR) have important roles in the development of HNSCC. The tyrosine kinase inhibitors, nilotinib, dasatinib, erlotinib and gefitinib are well established in the targeted therapy of tumors other than HNSCC. The present study aimed to investigate the alteration of MMP-9 and VEGFR-1 expression patterns following treatment with these tyrosine kinase inhibitors in p16-positive and -negative squamous carcinoma cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28515256/opportunities-and-challenges-human-papillomavirus-and-cancer
#6
Christina S Chu, David G Pfister
Mucosal exposure to human papillomavirus (HPV) can lead to anogenital and head and neck (H&N) cancer. Vaccination at a young age can be almost 100% effective in preventing HPV infection with the viral subtypes in both men and women, at least for disease in the anogenital tract. Therapeutic strategies targeting HPV in cervical dysplasia and cancer are showing promise as well in regressing dysplasia and controlling disease. That HPV-positive H&N cancer is a different disease from HPV-negative disease, with different molecular and clinical features and prognosis, is becoming better appreciated...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28488581/repurposing-albendazole-new-potential-as-a-chemotherapeutic-agent-with-preferential-activity-against-hpv-negative-head-and-neck-squamous-cell-cancer
#7
Farhad Ghasemi, Morgan Black, Frederick Vizeacoumar, Nicole Pinto, Kara M Ruicci, Carson Cao Son Huu Le, Matthew R Lowerison, Hon Sing Leong, John Yoo, Kevin Fung, Danielle MacNeil, David A Palma, Eric Winquist, Joe S Mymryk, Paul C Boutros, Alessandro Datti, John W Barrett, Anthony C Nichols
Albendazole is an anti-helminthic drug that has been shown to exhibit anti-cancer properties, however its activity in head and neck squamous cell cancer (HNSCC) was unknown. Using a series of in vitro assays, we assessed the ability of albendazole to inhibit proliferation in 20 HNSCC cell lines across a range of albendazole doses (1 nM-10 μM). Cell lines that responded to treatment were further examined for cell death, inhibition of migration and cell cycle arrest. Thirteen of fourteen human papillomavirus-negative HNSCC cell lines responded to albendazole, with an average IC50 of 152 nM...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28487502/pdcd1-pd-1-promoter-methylation-predicts-outcome-in-head-and-neck-squamous-cell-carcinoma-patients
#8
Diane Goltz, Heidrun Gevensleben, Joern Dietrich, Friederike Schroeck, Luka de Vos, Freya Droege, Glen Kristiansen, Andreas Schroeck, Jennifer Landsberg, Friedrich Bootz, Dimo Dietrich
BACKGROUND: Biomarkers that facilitate the prediction of disease recurrence in head and neck squamous cell carcinoma (HNSCC) may enable physicians to personalize treatment. In the current study, DNA promoter methylation of programmed cell death 1 (PDCD1, PD-1) was evaluated as a prognostic biomarker in HNSCC patients. RESULTS: High PDCD1 methylation (mPDCD1) was associated with a significantly shorter overall survival after surgical resection in both the discovery (HR = 2...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28484898/virus-induced-cancers-of-the-skin-and-mucosa-are-we-dealing-with-smoking-guns-or-smoke-and-mirrors-in-the-operating-theatre
#9
Peter K C Goon, Patrick K Y Goon, Eunice K H Tan, Robin A F Crawford, Nick J Levell, Holger Sudhoff
INTRODUCTION: Human papillomavirus (HPV) alone is thought to cause ~610,000 cases of cancer per year, and is the dominant aetiological agent for ano-genital (esp. cervical) and head and neck cancers (esp. oropharyngeal). Merkel cell polyomavirus (MCV) is a more recently discovered virus which causes Merkel cell carcinoma, a rare but highly aggressive skin malignancy. METHODS: We explored the available published evidence to see if transmission of live HPV or MCV virus in smoke generated by laser or diathermy was feasible, and would pose an infection risk...
May 8, 2017: Dermatology and Therapy
https://www.readbyqxmd.com/read/28480996/the-pd-1-pd-l1-axis-and-human-papilloma-virus-in-patients-with-head-and-neck-cancer-after-adjuvant-chemoradiotherapy-a-multicentre-study-of-the-german-cancer-consortium-radiation-oncology-group-dktk-rog
#10
Panagiotis Balermpas, Franz Rödel, Mechthild Krause, Annett Linge, Fabian Lohaus, Michael Baumann, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Eleni Gkika, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Stefan Stangl, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Gabriele Multhoff, Stephanie E Combs, Stefan Welz, Daniel Zips, Su Yin Lim, Claus Rödel, Emmanouil Fokas
We examined the prognostic role of PD-1+ and CD8+ tumor infiltrating lymphocytes (TILs), and PD-L1+ cells in patients with squamous cell carcinoma of the head and neck (SCCHN) treated with surgery and postoperative chemoradiotherapy (CRT). FFPE samples from 161 patients were immunohistochemically stained for PD-1, CD8 and PD-L1. The immune marker expression was correlated with clinicopathologic characteristics, and overall survival (OS), local progression-free survival (LPFS) and distant metastases free-survival (DMFS), also in the context of HPV16 DNA/p16 status...
May 8, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28479691/prevalence-of-human-papillomavirus16-dna-and-p16-ink4a-protein-in-oral-squamous-cell-carcinoma-a-systematic-review-and-meta-analysis
#11
T Smitha, C V Mohan, S Hemavathy
BACKGROUND AND AIM: Indian patients with oral squamous cell carcinoma (OSCC) are etiologically associated with the use of tobacco and alcohol; yet, a proportion of tumors that may harbor human papillomavirus (HPV) infections cannot be neglected. The following meta-analysis was conducted to address the association of p16(INK4a) and HPV DNA with OSCC. In addition, the study also provides the updated prevalence of HPV-induced OSCC. MATERIALS AND METHODS: Literature survey was performed using databases such as PubMed with the help of the following keywords - "HPV infection," "oral squamous cell carcinoma," "p16(INK4a)," "HPV DNA," "E6," "E7," "L1," "L2" and "LCR...
January 2017: Journal of Oral and Maxillofacial Pathology: JOMFP
https://www.readbyqxmd.com/read/28478912/quality-assurance-of-radiotherapy-in-the-ongoing-eortc-1219-dahanca-29-trial-for-hpv-p16-negative-squamous-cell-carcinoma-of-the-head-and-neck-results-of-the-benchmark-case-procedure
#12
Melissa Christiaens, Sandra Collette, Jens Overgaard, Vincent Gregoire, Joanna Kazmierska, Pierre Castadot, Jordi Giralt, Warren Grant, Milan Tomsej, Raquel Bar-Deroma, Angelo F Monti, Coen Wilhelm Hurkmans, Damien Charles Weber
BACKGROUND AND PURPOSE: The phase III EORTC 1219-DAHANCA 29 intergroup trial evaluates the influence of nimorazole in patients with locally advanced head and neck cancer when treated with accelerated radiotherapy (RT) in combination with chemotherapy. This article describes the results of the RT Benchmark Case (BC) performed before patient inclusion. MATERIALS AND METHODS: The participating centers were asked to perform a 2-step BC, consisting of (1) a delineation and (2) a planning exercise according to the protocol guidelines...
May 4, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28476872/integrative-analysis-identifies-a-novel-axl-pi3-kinase-pd-l1-signaling-axis-associated-with-radiation-resistance-in-head-and-neck-cancer
#13
Heath D Skinner, Uma Giri, Liang P Yang, Manish Kumar, Ying Liu, Michael D Story, Curtis R Pickering, Lauren A Byers, Michelle D Williams, Jing Wang, Li Shen, Suk Y Yoo, You Hong Fan, David P Molkentine, Beth M Beadle, Raymond E Meyn, Jeffrey N Myers, John V Heymach
Purpose: The primary cause of death due to head and neck squamous cell carcinoma (HNSCC) is local treatment failure. The goal of this study was to examine this phenomenon using an unbiased approach.Experimental Design: We utilized human papilloma virus (HPV)-negative cell lines rendered radiation-resistant (RR) via repeated exposure to radiation, a panel of HPV-negative HNSCC cell lines and three cohorts of HPV-negative HNSCC tumors (n = 68, 97, and 114) from patients treated with radiotherapy and subjected to genomic, transcriptomic, and proteomic analysis...
May 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28474265/gene-expression-signatures-for-head-and-neck-cancer-patient-stratification-are-results-ready-for-clinical-application
#14
REVIEW
Luca Tonella, Marco Giannoccaro, Salvatore Alfieri, Silvana Canevari, Loris De Cecco
Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer by incidence worldwide and considering the recent EUROCARE-5 population-based study the 5-year survival rate of HNSCC patients in Europe ranges between 69% in localized cases and 34% in patients with regional involvement. The development of high-throughput gene expression assays in the last two decades has provided the invaluable opportunity to improve our knowledge on cancer biology and to identify predictive signatures in the most deeply analyzed malignancies, such as hematological and breast cancers...
May 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28442504/characterization-of-the-tumor-t-cell-receptor-repertoire-and-immune-microenvironment-in-patients-with-locoregionally-advanced-squamous-cell-carcinoma-of-the-head-and-neck
#15
Vassiliki Saloura, Aiman Fatima, Makda Zewde, Kazuma Kiyotani, Ryan J Brisson, Jae-Hyun Park, Yuji Ikeda, Theodore Vougiouklakis, Riyue Bao, Tanguy Y Seiwert, Nicole A Cipriani, Mark W Lingen, Everett E Vokes, Yusuke Nakamura
Squamous cell carcinoma of the head and neck (SCCHN) is a lethal cancer with a suboptimal 5-year overall survival of approximately 50% with surgery and/or definitive chemoradiotherapy. Novel treatments are thus urgently awaited. Immunotherapy with checkpoint blockade has emerged as a promising option for patients with recurrent/metastatic SCCHN, however it has not been investigated in the curative-intent setting yet. The purpose of this study was to investigate the T-cell receptor repertoire and the tumor microenvironment in tumor tissues of SCCHN patients with locoregionally advanced disease...
April 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28441771/hepatocyte-growth-factor-c-met-signaling-in-head-and-neck-cancer-and-implications-for-treatment
#16
REVIEW
Natalie J Rothenberger, Laura P Stabile
Aberrant signaling of the hepatocyte growth factor (HGF)/c-Met pathway has been identified as a promoter of tumorigenesis in several tumor types including head and neck squamous cell carcinoma (HNSCC). Despite a relatively low c-Met mutation frequency, overexpression of HGF and its receptor c-Met has been observed in more than 80% of HNSCC tumors, with preclinical and clinical studies linking overexpression with cellular proliferation, invasion, migration, and poor prognosis. c-Met is activated by HGF through a paracrine mechanism to promote cellular morphogenesis enabling cells to acquire mesenchymal phenotypes in part through the epithelial-mesenchymal transition, contributing to metastasis...
April 24, 2017: Cancers
https://www.readbyqxmd.com/read/28438299/can-gene-editing-and-silencing-technologies-play-a-role-in-the-treatment-of-head-and-neck-cancer
#17
REVIEW
Mushfiq H Shaikh, Daniel T W Clarke, Newell W Johnson, Nigel A J McMillan
Conventional treatment strategies have done little to improve the prognosis or disease-free survival in head and neck cancer (HNC) patients. Recent progress in our understanding of molecular aspects of head and neck squamous cell carcinoma (HNSCC) has provided insights into the potential use of molecular targeted therapies in combination with current treatment strategies. Here we review the current understanding of treatment modalities for both HPV-positive and HPV-negative HNSCCs with the potential to use gene editing and silencing technologies therapeutically...
May 2017: Oral Oncology
https://www.readbyqxmd.com/read/28438296/discussing-hpv-with-oropharyngeal-cancer-patients-a-cross-sectional-survey-of-attitudes-in-health-professionals
#18
Rachael H Dodd, Alice S Forster, Jo Waller, Laura A V Marlow
BACKGROUND: Human papillomavirus (HPV) is now known to cause a significant proportion of head and neck cancers (HNC). Qualitative research has shown that some health professionals find it difficult to discuss HPV with patients due to its sexually transmitted nature, and have concerns about their own knowledge of the virus. We used a survey to quantify attitudes towards discussing HPV among HNC health professionals. METHODS: We carried out a cross-sectional survey of HNC health professionals (n=260) in the UK and Ireland, assessing participants' knowledge of HPV, their experiences of and attitudes towards discussing HPV with patients, and their willingness to discuss HPV with their patients in the future...
May 2017: Oral Oncology
https://www.readbyqxmd.com/read/28438294/a-model-using-concomitant-markers-for-predicting-outcome-in-human-papillomavirus-positive-oropharyngeal-cancer
#19
Cinzia Bersani, Michael Mints, Nikolaos Tertipis, Linnea Haeggblom, Lars Sivars, Andreas Ährlund-Richter, Andrea Vlastos, Cecilia Smedberg, Nathalie Grün, Eva Munck-Wikland, Anders Näsman, Torbjörn Ramqvist, Tina Dalianis
OBJECTIVE: Head-neck cancer therapy has become intensified. With radiotherapy alone, 3-year disease-free survival (DFS) is 80% for HPV-positive TSCC/BOTSCC and better for patients with favorable characteristics, suggesting therapy could be tapered for some, decreasing side-effects. Therefore, we built a model to predict progression-free survival for patients with HPV-positive TSCC and BOTSCC. MATERIAL AND METHODS: TSCC/BOTSCC patients treated curatively between 2000 and 2011, with HPV16 DNA/E7 mRNA positive tumors examined for CD8(+) TILs, HPV16 mRNA and HLA class I expression were included...
May 2017: Oral Oncology
https://www.readbyqxmd.com/read/28437708/primary-secondary-and-tertiary-prevention-of-human-papillomavirus-driven-head-and-neck-cancers
#20
REVIEW
Haïtham Mirghani, Alain C Jung, Carole Fakhry
Human papillomavirus (HPV)-driven oropharyngeal cancers (OPCs) represent an increasing proportion of head and neck cancers that could become, in the next few decades, a public health problem in certain western countries. This significant epidemiological change strongly calls for preventive measures. Prophylactic HPV vaccination and screening programmes for early identification and treatment of premalignant lesions are currently being used to reduce the incidence of uterine cervical cancer, which is the paradigm of HPV-driven malignancy...
April 19, 2017: European Journal of Cancer
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