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      Call for Papers: Beyond Biology: The Crucial Role of Sex and Gender in Oncology

      Submit here before July 31, 2024

      About Oncology Research and Treatment: 2.0 Impact Factor I 3.2 CiteScore I 0.521 Scimago Journal & Country Rank (SJR)

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      Update on Head and Neck Cancer: Current Knowledge on Epidemiology, Risk Factors, Molecular Features and Novel Therapies

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          Abstract

          Tobacco use and alcohol consumption are the main risk factors associated with head and neck squamous cell carcinoma (SCC) development due to their cytotoxic and mutagenic effects on the exposed epithelia of the upper aerodigestive tract. Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HPVs), both encoding viral oncoproteins able to interfere with cell cycle control, have been recognized as the etiological agents of nasopharynx carcinoma and a fraction of oropharyngeal carcinoma, respectively. Head and neck SCC is a deadly disease and despite innovative treatments represents a major challenge for patients. Recently, a number of genomic studies have highlighted the molecular heterogeneity of head and neck SCC based on methylation profiles, microRNA expression, mutated genes and new druggable pathways which may represent new targets for cancer-tailored therapies. To date, cetuximab is the only FDA-approved anti-epidermal growth factor receptor therapy for the treatment of head and neck SCC. In addition, a number of monoclonal antibodies targeting AKT, mTOR and PI3K pathways are under evaluation. Several therapeutic vaccines against HPV16 and EBV proteins are also under study. The purpose of this article is to review the epidemiology, pathogenesis and molecular features of head and neck SCC, with an emphasis on new therapies.

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          Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1.

          N. Agrawal, M Frederick, C. R. Pickering … (2011)
          Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. To explore the genetic origins of this cancer, we used whole-exome sequencing and gene copy number analyses to study 32 primary tumors. Tumors from patients with a history of tobacco use had more mutations than did tumors from patients who did not use tobacco, and tumors that were negative for human papillomavirus (HPV) had more mutations than did HPV-positive tumors. Six of the genes that were mutated in multiple tumors were assessed in up to 88 additional HNSCCs. In addition to previously described mutations in TP53, CDKN2A, PIK3CA, and HRAS, we identified mutations in FBXW7 and NOTCH1. Nearly 40% of the 28 mutations identified in NOTCH1 were predicted to truncate the gene product, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type.
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            Human Papillomavirus Types in Head and Neck Squamous Cell Carcinomas Worldwide: A Systematic Review

            A. Kreimer (2005)
            Mucosal human papillomaviruses (HPV) are the cause of cervical cancer and likely a subset of head and neck squamous cell carcinomas (HNSCC), yet the global prevalence and type distribution of HPV in HNSCC remains unclear. We systematically reviewed published studies of HNSCC biopsies that employed PCR-based methods to detect and genotype HPV to describe the prevalence and type distribution of HPV by anatomic cancer site. Geographic location and study size were investigated as possible sources of variability. In the 5,046 HNSCC cancer specimens from 60 studies, the overall HPV prevalence was 25.9% [95% confidence interval (95% CI), 24.7-27.2]. HPV prevalence was significantly higher in oropharyngeal SCCs (35.6% of 969; 95% CI, 32.6-38.7) than oral SCCs (23.5% of 2,642; 95% CI, 21.9-25.1) or laryngeal SCCs (24.0% of 1,435; 95% CI, 21.8-26.3). HPV16 accounted for a larger majority of HPV-positive oropharyngeal SCCs (86.7%; 95% CI, 82.6-90.1) compared with HPV-positive oral SCCs (68.2%; 95% CI, 64.4-71.9) and laryngeal SCCs (69.2%; 95% CI, 64.0-74.0). Conversely, HPV18 was rare in HPV-positive oropharyngeal SCCs (2.8%; 95% CI, 1.3-5.3) compared with other head and neck sites [34.1% (95% CI, 30.4-38.0) of oral SCCs and 17.0% (95% CI, 13.0-21.6) of laryngeal SCCs]. Aside from HPV16 and HPV18, other oncogenic HPVs were rarely detected in HNSCC. Tumor site-specific HPV prevalence was higher among studies from North America compared with Europe and Asia. The high HPV16 prevalence and the lack of HPV18 in oropharyngeal compared with other HNSCCs may point to specific virus-tissue interactions. Small sample size and publication bias complicate the assessment of the prevalence of HPV in head and neck sites beyond the oropharynx.
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              Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers.

              Curtis R. Pickering, Jiexin Zhang, Suk Young Yoo … (2013)
              The survival of patients with oral squamous cell carcinoma (OSCC) has not changed significantly in several decades, leading clinicians and investigators to search for promising molecular targets. To this end, we conducted comprehensive genomic analysis of gene expression, copy number, methylation, and point mutations in OSCC. Integrated analysis revealed more somatic events than previously reported, identifying four major driver pathways (mitogenic signaling, Notch, cell cycle, and TP53) and two additional key genes (FAT1, CASP8). The Notch pathway was defective in 66% of patients, and in follow-up studies of mechanism, functional NOTCH1 signaling inhibited proliferation of OSCC cell lines. Frequent mutation of caspase-8 (CASP8) defines a new molecular subtype of OSCC with few copy number changes. Although genomic alterations are dominated by loss of tumor suppressor genes, 80% of patients harbored at least one genomic alteration in a targetable gene, suggesting that novel approaches to treatment may be possible for this debilitating subset of head and neck cancers.
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                Author and article information

                Journal
                Journal ID (publisher-id): OCL
                Journal ID (nlm-ta): Oncology
                Journal ID (doi): 10.1159/issn.0030-2414
                Title: Oncology
                Publisher: S. Karger AG
                ISSN (Print): 0030-2414
                ISSN (Electronic): 1423-0232
                Publication date Subscription-year: 2015
                Publication date (Print): August 2015
                Publication date (Electronic): 08 May 2015
                Volume: 89
                Issue: 3
                Pages: 125-136
                Affiliations
                aMolecular Biology and Viral Oncology Unit, bOncologia Medica Testa-Collo e Sarcoma, and cChirurgia Oncologica Maxillo-Facciale ed ORL, Istituto Nazionale Tumori ‘Fondazione G. Pascale' - IRCCS, Naples, Italy
                Author notes
                *Dr. Maria Lina Tornesello, Molecular Biology and Viral Oncology Unit, Istituto Nazionale Tumori ‘Fondazione G. Pascale' - IRCCS, Via M. Semmola, IT-80131 Naples (Italy), E-Mail m.tornesello@istitutotumori.na.it
                Author information
                https://orcid.org/0000-0002-3523-3264
                Article
                Publisher ID: 381717 Other ID: Oncology 2015;89:125-136
                DOI: 10.1159/000381717
                PubMed ID: 25967534
                SO-VID: 6f13f3cd-37f8-4083-b6fa-3a8054b9df99
                Copyright © © 2015 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 04 December 2014
                Date accepted : 16 March 2015
                Page count
                Figures: 2, Tables: 1, References: 58, Pages: 12
                Categories
                Subject: Review

                ScienceOpen disciplines: Oncology & Radiotherapy,Pathology,Surgery,Obstetrics & Gynecology,Pharmacology & Pharmaceutical medicine,Hematology
                Keywords: Head and neck cancer,Epstein-Barr virus,Tumorigenesis,Human papillomavirus
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy, Pathology, Surgery, Obstetrics & Gynecology, Pharmacology & Pharmaceutical medicine, Hematology
                Keywords: Head and neck cancer, Epstein-Barr virus, Tumorigenesis, Human papillomavirus

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