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Advances in the management of squamous cell carcinoma of the head and neck

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      Abstract

      Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer worldwide. The main risk factors for cancers of the oral cavity, larynx, oropharynx, and hypopharynx are alcohol and tobacco use. In addition, the human papillomavirus (HPV) is an established cause of oropharyngeal cancer. An experienced multidisciplinary team is necessary for adequate management and optimal outcome. The treatment of locally advanced disease generally requires various combinations of radiotherapy, surgery, and systemic therapy, but despite this aggressive multimodal treatment, 40% to 60% of the patients will relapse. In this report, we will discuss recent advances in the management of SCCHN, including new developments in molecular biology, imaging, and treatment.

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      Most cited references 113

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      Human papillomavirus and survival of patients with oropharyngeal cancer.

      Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown. We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer. The median follow-up period was 4.8 years. The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving standard-fractionation radiotherapy (70.3% vs. 64.3%; P=0.18; hazard ratio for death with accelerated-fractionation radiotherapy, 0.90; 95% confidence interval [CI], 0.72 to 1.13), as were the rates of high-grade acute and late toxic events. A total of 63.8% of patients with oropharyngeal cancer (206 of 323) had HPV-positive tumors; these patients had better 3-year rates of overall survival (82.4%, vs. 57.1% among patients with HPV-negative tumors; P<0.001 by the log-rank test) and, after adjustment for age, race, tumor and nodal stage, tobacco exposure, and treatment assignment, had a 58% reduction in the risk of death (hazard ratio, 0.42; 95% CI, 0.27 to 0.66). The risk of death significantly increased with each additional pack-year of tobacco smoking. Using recursive-partitioning analysis, we classified our patients as having a low, intermediate, or high risk of death on the basis of four factors: HPV status, pack-years of tobacco smoking, tumor stage, and nodal stage. Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer. (ClinicalTrials.gov number, NCT00047008.) 2010 Massachusetts Medical Society
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        Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck.

        We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck. Patients with locoregionally advanced head and neck cancer were randomly assigned to treatment with high-dose radiotherapy alone (213 patients) or high-dose radiotherapy plus weekly cetuximab (211 patients) at an initial dose of 400 mg per square meter of body-surface area, followed by 250 mg per square meter weekly for the duration of radiotherapy. The primary end point was the duration of control of locoregional disease; secondary end points were overall survival, progression-free survival, the response rate, and safety. The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone (hazard ratio for locoregional progression or death, 0.68; P=0.005). With a median follow-up of 54.0 months, the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone (hazard ratio for death, 0.74; P=0.03). Radiotherapy plus cetuximab significantly prolonged progression-free survival (hazard ratio for disease progression or death, 0.70; P=0.006). With the exception of acneiform rash and infusion reactions, the incidence of grade 3 or greater toxic effects, including mucositis, did not differ significantly between the two groups. Treatment of locoregionally advanced head and neck cancer with concomitant high-dose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck. (ClinicalTrials.gov number, NCT00004227.) Copyright 2006 Massachusetts Medical Society.
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          The mutational landscape of head and neck squamous cell carcinoma.

          Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.
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            Author and article information

            Affiliations
            Clinique de cancérologie cervico-maxillo-faciale, Centre du cancer et d'hématologie, Cliniques universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (IREC), Université catholique de Louvain 10 Avenue Hippocrate, 1200 BrusselsBelgium
            Contributors
            Journal
            F1000Prime Rep
            F1000Prime Rep
            F1000Prime Reports
            Faculty of 1000 Ltd
            2051-7599
            02 June 2014
            2014
            : 6
            4047945
            10.12703/P6-44
            44
            © 2014 Faculty of 1000 Ltd

            All F1000Prime Reports articles are distributed under the terms of the Creative Commons Attribution-Non Commercial License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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