Early Detection and Treatment of Head and Neck Cancers: Theoretical Background and Newly Emerging Research

Head and neck cancer (HNC) is a heterogeneous group of cancers that, if combined, represent one of the most common cancer types. Patients with HNC suffer significant morbidity and mortality due to the importance of the structures involved. Over two-thirds of these patients are diagnosed at a late stage, leading to a poor prognosis. Therefore, advancements in early detection and treatment of HNC are crucial. This second volume provides an up-to-date overview of the theoretical background in the field of head and neck cancer (HNC) as well as of the emerging research that is impacting our understanding of this disease. The book begins with a comprehensive review of the epidemiology, etiology, symptoms, diagnosis, and staging of HNC. Next, it covers the essentials of potentially malignant disorders of the oral cavity, an important variety of HNC. Subsequently, it covers the newly emerging research in the field of HNC. The overall goal is to shift towards precision medicine (discussed in detail in Volume I), which will bring individualized clinical benefit to patients with HNC. This second volume of Early Detection and Treatment of Head & Neck Cancers concludes with the topic of chronic pain associated with HNC, including both the mechanisms of pain and the management strategies, and the emerging oral mucoadhesive drug delivery approach for HNC. All HNC surgeons, scientists, residents, and individuals whose lives have been touched by this disease, will recognize the impact pain has upon a patient's health and his or her recovery trajectory. Foreword Acknowledgments A Historic Perspective Preface Contents Contributors Chapter 1: General Introduction to Head and Neck Cancer: Etiology, Symptoms, Diagnosis, Staging, Prevention, and Treatment Introduction Epidemiology Etiology Tobacco Alcohol Alcohol and Tobacco in Combination Viruses Immunosuppressive Agents Diet Oral Hygiene Diseases Oral Microbiota Socioeconomic Status Free Radicals Atmospheric Gases Occupational Exposures Other Risk Factors Symptoms Diagnosis Clinical Examination Imaging Probing Tumor Biopsy Pathology/Immunohistochemistry Staging System Prevention Treatment Stagewise Treatment for HNC Early Stage HNC Stage III/IV Cancers Metastatic Disease Perspective References Chapter 2: Potentially Malignant Disorders of the Oral Cavity Introduction Oral Potentially Malignant Disorders (OPMDs) Leukoplakia Erythroplakia Oral Submucous Fibrosis Diagnosis and Screening of OPMDs Noninvasive Techniques Vital Staining Light-Based Detection Systems Chemiluminescence Tissue Autofluorescence Photodynamic Techniques Optical Diagnostic Technologies Prognostic Molecular Biomarkers Invasive Detection Techniques Incisional Biopsy Oral Brush Cytology (OBC) Conclusion References Chapter 3: Diagnosis and Management of Intraoral Epithelial Dysplasia Introduction Aids in the Diagnosis of Oral Dysplasia Special Emphasis on Other Differential Diagnosis Proliferative Verrucous Leukoplakia Lichen Planus Treatment of Intraoral Dysplasia How to Avoid the Development of Dysplasia and Oral Cancer Smoking Drinking Chewing Vitamin Imbalance Oncogenic Viruses Surprising Good Side Effects of Medications Conclusion References Chapter 4: Dysphagia in Head and Neck Cancers Introduction Surgical Management Oral Cavity Cancers Oropharyngeal and Nasopharyngeal Cancers Laryngeal and Hypopharyngeal Cancers Radiation Therapy Assessment of Swallowing Disorders in Head and Neck Cancers Medical History Clinical Oral Examination Instrumental Evaluation Treatment of Dysphagia in Head and Neck Cancers Diet Allocation Compensatory Strategies and Maneuvers Postural Changes Compensatory Strategies Swallowing Exercises Range of Motion and Strengthening Exercises Multidisciplinary Team Conclusion References Chapter 5: The Mutational Landscape of Head and Neck Squamous Cell Carcinoma: Opportunities for Detection and Monitoring Via Analysis of Circulating Tumor DNA Introduction Mutational Landscape of HNSCC Comparison of Mutational Landscape of HPV-Positive and HPV-Negative HNSCC Alterations Associated with Early-Stage HNSCC Circulating Tumor DNA (ctDNA) in HNSCC Tumor Detection Tumor Monitoring Conclusions and Future Directions References Chapter 6: Circulating Biomarkers in Head and Neck Cancer Introduction Circulating Tumor DNA and Circulating Tumor Cells Early Detection Treatment Selection Monitoring Treatment Response Monitoring Minimal Residual Disease Predicting Metastasis Circulating Exosomal miRNAs Salivary Diagnostics Salivary ctDNA Salivary miRNA Salivary Exosomes Conclusions and Future Perspectives References Chapter 7: Proinflammatory Signaling Pathways and Genomic Signatures in Head and Neck Cancers Introduction Networks of Proinflammatory Cytokines, Chemokines, and Growth Factors Role of Interleukins, Chemokines, and Growth Factors in HNC Pathogenesis Co-expression of Proinflammatory Factors as Clinical Correlates Cytokine- and Chemokine-Based Therapies and Their Potentials NF-κB Pathway and Crosstalk with Other Signaling in Head and Neck Cancers Classical and Alternative NF-κB Signaling Pathways Crosstalk of NF-κB Pathway with Other Signaling Pathways Current Biomarkers and Drug Development Related to NF-κB Pathways Regulation of Inflammatory Signaling by Ubiquitination and Proteasome The Ubiquitin System Ubiquitin-Mediated Regulation of Inflammatory Signaling The Ubiquitin System in HNSCC: Genomic and Transcriptomic Expression Data Copy-Number Alteration and mRNA Expression Somatic Mutations Targeting the Ubiquitin System in HNSCC Proteasome Inhibitors IAP Antagonists Genomic Signatures and Transcriptomic Landscapes of Proinflammatory and Other Signaling Molecules Overview of TCGA Project and the Individual Biomarker Paper of HNSCC Three Major Themes of TCGA Pan-Cancer Atlas Project Include “Cell of Origin,” “Oncogenic Process,” and “Signaling Pathways” Landscape Characterization of Human Cell Lines Using High-Throughput Technologies Genome-Wide Gene Perturbation and Interrogation with Functional Analyses Overall Conclusions and Future Directions References Chapter 8: Pain Associated with Head and Neck Cancers Introduction Mechanisms of Head and Neck Cancer Pain Nerve Growth Factor Endothelin-1 Proteases and Protease-Activated Receptors How Treatment Modalities Can Cause Pain? Chronic Pain Pathophysiology Modulation New Frontiers Compounded Analgesic Formulations Tapentadol Cebranopadol and NKTR-181 Neurochemistry Future Perspective References Chapter 9: Emerging Trends in Oral Mucoadhesive Drug Delivery for Head and Neck Cancer Introduction Histological Structure of the Oral Mucosa and Saliva Components The Epithelial Layer The Basement Membrane The Connective Tissue Saliva, Mucus, and Mucins Mucoadhesive Theories Diffusion Theory Electronic Theory Absorption Theory Fracture Theory Wetting Theory Oral Mucoadhesive Drug Delivery System Formulations for Head and Neck Cancer Solids Tablets Wafers Bioadhesive Microspheres Semisolids Films and Patches Chewing Gum Ointment or Gel Liquids or Suspensions Components of Oral Mucoadhesive Drug Delivery Systems Drug Substance Bioadhesive Polymers Backing Membrane Plasticizers Permeation Enhancers Conclusion References Index The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. 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