Head and Neck Cancer (eBook)

Front Cover 1
Head and Neck Cancer: Emerging Perspectives 4
Copyright Page 5
Contents 6
Contributors 14
Foreword 18
PART I: INTRODUCTION 20
Chapter 1. Clinical Perspectives in Head and Neck Cancer 22
I. Clinical Patterns in Head and Neck Cancer 22
II. Human Cancer Surrogates and Models 24
III. Translational or Correlative Cancer Research 25
IV. Conclusion 25
References 26
Chapter 2. Head and Neck Cancers with Unusual Natural Histories 28
a. Unknown Primary Carcinoma Metastatic to Cervical Nodes 28
I. Introduction 28
II. Clinical Presentation 28
III. Evaluation 29
IV. Treatment 31
V. Treatment Results 32
References 34
b. Adenoid Cystic Carcinoma 35
I. Introduction 35
II. Incidence 35
III. Natural History 36
IV. Pathology 36
V. Evaluation 37
VI. Treatment 38
VII. Results 38
References 40
Chapter 3. Head and Neck Cancer Imaging 42
I. Head and Neck Cancer Imaging 42
II. Anatomic Cross-Sectional Imaging Techniques for the Head and Neck 42
III. Positron Emission Tomography (PET) 43
IV. Staging Head and Neck Cancer 44
V. Evaluation of Therapy of Head and Neck Cancer 47
VI. Assessment of Recurrent Head and Neck Cancer 50
VII. Conclusion 51
References 51
Chapter 4. Preneoplastic Lesions of the Upper Aerodigestive Tract 54
I. Introduction 54
II. Normal Anatomy 54
III. Pathological Features 56
IV. Clinical Features 64
V. Correlation between Clinical and Histological Findings 66
VI. Malignant Progression 67
References 69
PART II: BASIC MOLECULAR MECHANISMS 74
Chapter 5. Animal Models in Head and Neck Cancer 76
I. Introduction 76
II. History of Experimental Head and Neck Cancer Research 76
III. Genetic Models for Head and Neck Cancer Research 78
IV. Integrative Human-Based Discoveries and Animal Model Testing for Head and Neck Cancer Research 80
References 80
Chapter 6. Adhesion Receptors in Oral Cancer Invasion 84
I. Introduction 84
II. Cell–Substrate Adhesion 85
III. Extracellular Matrix-lntegrins Interactions and Signal Transduction 89
IV. Cadherins and Intracellular Adhesion 90
V. Conclusions 93
References 93
Chapter 7. Angiogenesis, Basic Mechanisms, and Role in Head and Neck Squamous Cell Carcinoma 100
I. Epidemiology, Pathology, and Biology of Head and Neck Squamous Cell Carcinoma (HNSCC) 100
II. Basic Mechanisms of Angiogenesis 101
III. Angiogenesis in HNSCC 102
IV. Antiangiogenic Therapies in HNSCC 110
V. Conclusions 111
References 111
Chapter 8. Cell Cycle Regulatory Mechanisms in Head and Neck Squamous Cell Carcinoma 120
I. Introduction 120
II. Progression through the Mammalian Cell Cycle 120
III. Cyclin-Dependent Kinase Inhibitors (CKIs) 123
IV. Alterations in Cell Cycle Regulators 127
References 129
Chapter 9. Oncogenes and Tumor Suppressor Genes in Oral or Head and Neck Squamous Cell Carcinoma 136
I. Introduction 136
II. Cancer 137
III. Cell Regulation, Oncogenes, and Tumor Suppressor Genes 137
IV. Tumor Suppressor Genes 139
V. Detection of Individuals at Risk 144
VI. Molecular Diagnosis 144
VII. Staging 144
VIII. Prognostication 144
References 145
Chapter 10. Proteolysis in Carcinogenesis 156
I. Tumor-Associated Protease Systems 156
II. Molecular Targets for Proteases in Tumor Progression 159
III. Extracellular Proteolysis in Head and Neck Cancer Progression 162
References 163
Chapter 11 . Papillomaviruses in Head and Neck Squamous Cell Carcinoma 170
I. Introduction 170
II. Human Papillomaviruses (HPVs) 171
III. Interaction between Cellular Host Factors and E6 of High-Risk HPVs 172
IV. Interaction between Cellular Host Factors and E7 of High-Risk HPVs 173
V. Methods of Detection of HPVs 174
V1. HPV and Normal Mucosa of the Upper Aerodigestive Tract 174
VII. HPV and Benign Lesions of the Head and Neck 175
VIII. HPVs and Premalignant Lesions of the Head and Neck 176
IX. HPV and SCCA of Head and Neck 178
X. Conclusions 180
References 181
Chapter 12. Clinical Correlations of DNA Content Parameters, DNA Ploidy, and S-Phase Fraction in Head and Neck Cancer 186
I. Introduction 186
II. Technical Considerations 187
III. DNA Content Parameters for Squamous Cell Carcinomas of the Head and Neck 188
IV. DNA Content Parameters and Nonsquamous Cell Carcinomas of the Head and Neck 195
V. Multiparameter Studies 196
VI. Conclusions 197
References 198
PART III: PREVENTION AND DETECTION 202
Chapter 13. Smoking Behavior and Smoking Cessation among Head and Neck Cancer Patients 204
I. Introduction 204
II. Adverse Effects of Smoking for Head and Neck Cancer Patients 205
III. Smoking Rates among Head and Neck Cancer Patients 206
IV. Why Head and Neck Cancer Patients May Have Trouble Quitting Smoking 207
V. Stage of the Science in Smoking Cessation Interventions 211
VI. Directions for Future Research 214
References 215
Chapter 14. Nutrients, Phytochemicals, and Squamous Cell Carcinoma of the Head and Neck 220
I. Introduction 220
II. Tobacco and Nutrients 221
III. Alcohol and Nutrients 222
IV. Cancer Treatment and Nutrients 222
V. Nutritional Consequences of Radiation and Chemotherapy 222
VI. Effects of Selected Micronutrients on Radiation and Chemotherapy Toxicity 223
VII. Nutrients and Antitumor Effects of Radiation/Chemotherapy 224
VIII. Nutrients and Pharmaceuticals in the Prevention of Radiation and Chemotherapy Toxicity 225
IX. Conclusions 227
References 227
Chapter 15. Molecular Epidemiology of Head and Neck Cancer 232
I. Introduction 232
II. Epidemiology of Head and Neck Cancer 232
III. Molecular Epidemiology of Head and Neck Cancer 234
IV. Xenobiotic Metabolism of Carcinogens in Head and Neck Cancer 234
V. DNA Repair Phenotype and Risk of Head and Neck Cancer 235
VI. Polymorphisms in DNA Repair Genes 238
VII. Polymorphisms in Cell Cycle Genes 239
References 240
Chapter 16. Head and Neck Field Carcinogenesis 246
I. Introduction 246
II. Clinical Evidence for Head and Neck Field Cancerization 248
III. Histopathologic Evidence of Field Cancerization 249
IV. Genetic Evidence for Field Cancerization 250
V. Phenotypic Changes Associated with Field Carcinogenesis 255
VI. Clinical Implication of Field Cancerization 255
References 257
Chapter 17. Molecular Markers of Oral Premalignant Lesion Risk 264
1. Introduction 264
II. Oral Premalignant Lesions (OPLs): Traditional and Evolving Definitions 265
III. Lack of a Reliable System for Predicting Progression Risk of OPLs 266
IV. Lack of a Consensus on Treatment for OPLs 266
V. Use of Microsatellite Analysis to Identify Oral 248 Mucosal Regions at Risk for Progression 267
VI. Use of Molecular Markers to Manage OPLs 270
VII. Exfoliated Cell Sampling: A Noninvasive Method for Identification, Risk Prediction, and Management of OPLs 272
VIII. The Need for Longitudinal Studies 274
References 275
Chapter 18. Chemoprevention of Oral Premalignant Lesions 280
I. Oral Premalignant Lesions: Definition and Significance 280
II. Chemoprevention Trials: General Design and Outcome Assessment 281
III. Review of Trials 282
IV. Validity of Oral Precancerous Lesions in Predicting Efficacy of Agents for Oral Cancer Prevention 285
V. Summary and Conclusions 286
References 287
Chapter 19. Aerodigestive Tract Chemoprevention Trials and Prevention of Second Primary Tumors 290
I. Introduction 290
II. Epidemiology 291
III. Natural History 291
IV. Risk Factors 292
V. Biology of Head and Neck Cancer 294
VI. Chemoprevention 295
VII. Chemoprevention Trials 295
VIII. Biochemoprevention 300
IX. Summary: Future Directions 300
References 300
Chapter 20. Statistical Methods for Biomarker Analysis for Head and Neck Carcinogenesis and Prevention 306
I. Introduction 306
II. Type of Biomarker Measures 307
III. Standard Statistical Methods for Analyzing Biomarkers 308
IV. Distribution of Continuous Biomarkers 309
V. Choosing Cut Points for Continuous Biomarkers 310
VI. Analysis of Surrogate End Point Biomarkers 311
VII. Predicting Cancer Development Using Clinical, Histological, Epidemiologic, and Multiple Biomarker Information 314
VIII. Summary and Design Considerations for Biomarker-Integrated Translational Studies 320
References 321
Chapter 21. Molecular Detection of Head and Neck Cancer 324
I. Introduction 324
II. Detection of Head and Neck Squamous Cell Carcinoma in Exfoliated Cell Samples 325
III. Detection of Circulating Tumor Markers 329
IV. Microarrays 330
V. Spectroscopic Analysis 330
VI. Diagnostic or Prognostic Biomarkers in Biopsy Material 330
VII. Conclusion 331
References 331
PART IV: CURRENT APPROACHES: IV. Risk Factors 273 Surgical Considerations 334
Chapter 22. Management of the Neck in Squamous Cell Carcinomas of the Head and Neck 336
I. Introduction 336
II. Incidence of Cervical Metastases 336
III. Patterns of Lymphatic Spread 338
IV. Prognostic Implications of Neck Node Metastases 339
V. Current Management of Lymph Nodes of theNeck 340
VI. Types of Neck Dissection 343
References 343
Chapter 23. Management of the Carotid Artery in Advanced Head and Neck Cancer 348
I. Management of the Carotid Artery in Advanced Head and Neck Cancer 348
II. Patent Presentation: Clinical and Radiological Diagnosis 348
III. Clinical Outcome 349
IV. Nonsurgical Treatment Options 350
V. Surgical Treatment Options 351
VI. Preoperative Evaluation 351
VII. Surgical Procedure 352
VIII. Postoperative Complications 354
IX. Conclusion 354
References 355
Chapter 24. Skull Base Surgery 358
I. Introduction 358
II. Evaluation of Patient 359
III. Anesthetic Considerations 360
IV. Physiological Monitoring 361
V. Pathology 361
VI. Surgery of Skull Base 365
VII. Complications 374
VIII. Conclusion 375
References 375
Chapter 25. Management of Laryngeal Cancer 378
I. Introduction 378
II. Treatment of Carcinoma in Situ and Minimally Invasive T, Glottic Cancer 379
III. Treatment of T1 Glottic Cancer 380
IV. Treatment of T2 Glottic Cancer 382
V. Treatment of T3 and T4 Glottic Cancer 385
VI. Treatment of Supraglottic Cancer 388
VII. Summary 390
References 391
Chapter 26. Partial Laryngeal Procedures 394
I. Introduction 394
II. Basic Concepts: Beyond Conservation Laryngeal Surgery to Organ Preservation Surgery of the Larynx 395
III. Principle One: Nonsurgical Organ Preservation Strategies versus Organ Preservation Surgery 396
IV. Principle Two: The Cricoarytenoid Unit 399
V. Principle Three: The Spectrum Concept of Laryngeal Carcinoma and Laryngeal Cancer Surgery 400
VI. Principle Four: Resection of Normal Tissue to Maintain Postoperative Function 401
VII. Principle Five: The Importance of Local Control 402
VIII. Organ Preservation Surgical Techniques 402
IX. Organ Preservation Surgery for Carcinomas Arising at the Glottic Level 403
X. Organ Preservation Surgery for Carcinomas Arising at the Supraglottic Level 405
XI. Summary 407
References 407
Chapter 27. High-Dose lntraarterial Chemotherapy/Radiation for Advanced Head and Neck Cancer 412
I. Introduction 412
II. RADPLAT Drug Delivery Technique 413
III. RADPLAT Results 414
IV. RADPLAT Experience at Other Centers 417
V. New Directions Using the RADPLAT Concept 418
VI. Conclusions 421
References 422
Chapter 28. Thyroid Cancer 424
I. Introduction 424
II. Molecular Basis for Thyroid Cancer 425
III. Risk Factors and Etiology 425
IV. Tumor Staging/Classification 426
V. Evaluation of a Thyroid Nodule 427
VI. Review of Thyroid Cancers 431
VII. Surgical Management and Technique 438
VIII. Postoperative Management and Special Considerations 445
IX. Conclusions 446
References 446
Chapter 29. Assessment of Outcomes in Head and Neck Cancer 452
I. Background 452
II. Survival 453
III. Determinant Survival 453
IV. Actuarial Survival 454
V. Kaplan–Meier Survival 455
VI. Morbidity 455
VII. Health Status 455
VIII. Quality of Life 457
IX. Cost of care 460
X. Summary 460
References 461
Nonsurgical Considerations 11
Chapter 30. Combination of Chemotherapy with Radiation for Head and Neck Cancer 464
I. Introduction 464
II. Radiotherapy Fractionation Regimes 464
III. Goals of Combining Chemotherapy and Radiation 466
IV. Randomized Studies of Induction Chemotherapy Followed by Locoregional Therapy 466
V. Randomized Trials Addressing Concurrent Chemotherapy with Radiation 468
VI. Meta-Analyses Addressing the Role of Chemotherapy 473
VII. Summary of Available Trial Results 475
VIII. Future Research Directions 476
References 478
Chapter 31 . Clinical Trials in Advanced Unresectable Head and Neck Cancer 480
I. Altered Fractionation Radiation 481
II. Induction Chemotherapy 482
III. Alternating Chemotherapy and Radiation 485
IV. Concurrent Chemotherapy and Radiation 485
V. Future Directions 488
References 489
Chapter 32. Organ Preservation in Head and Neck Cancer 494
I. Introduction 494
II. Laryngeal Preservation: Cancers of the Larynx and Hypopharynx 494
III. Role of Chemotherapy in Preservation of the Oropharynx 497
References 508
Chapter 33. Nasopharyngeal Cancer 510
I. Introduction 510
II. Epstein–Barr Virus 510
III. Genetics 511
IV. Environmental Factors 511
V. Anatomy 511
VI. Pathology 511
VII. Natural History 512
VIII. Workup 512
IX. Pretreatment Evaluation 512
X. Staging 512
XI. Radiation Therapy 513
XII. Volume Treated 513
XIII. Boost Volume 513
XIV. Dose Response 513
XV. Reirradiation 514
XVI. Survival 515
XVII. Chemotherapy 515
XVIII. Chemotherapy for Recurrent/Metastatic Disease 516
XIX. Chemotherapy for Locally Advanced and Previously Untreated Nasopharyngeal Cancer 517
XX. Induction Chemotherapy 517
XXI. Concurrent Chemoradiotherapy 518
XXII. Adjuvant Chemotherapy 518
XXIII. Randomized Trials 519
XXIV. Conclusion 520
References 520
PART V: NOVEL APPROACHES 526
Chapter 34. Squamous Carcinomas of the Head and Neck: Novel Genomic Approaches 528
I. Introduction 528
II. Genetic Alterations in Head and Neck Squamous Cell Carcinomas (HNSCC) 529
III. Techniques Used for Molecular Profiling of HNSCC 529
IV. Use of Gene Assays to Evaluate Gene Expression Profiles in HNSCC 533
V. Gene Discovery Efforts in HNSCC: The Cancer Genome Anatomy Project 533
VI. Proteomics 537
VII. Conclusion 538
References 538
Chapter 35. Molecular Assessment of Surgical Margins 542
I. Introduction 542
II. Insight from the Molecular Biology Revolution 543
III. The Margin Dilemma 543
IV. Technical Factors Influencing Margin Assessment 544
V. Is Margin Status Reflective of Biologic Aggressiveness? 546
VI. Theoretical Basis for Molecular Margin Analysis 547
VII. Published Molecular Margin Studies 547
VIII. Clinical Response to Positive Margins 549
IX. Concluding Remarks 550
References 551
Chapter 36. Novel Agents and Modalities for the Treatment of Squamous Carcinoma of the Head and Neck 554
I. Novel Targets and Agents for the Treatment of Advanced Head and Neck Squamous Cell Carcinoma (HNSCC) 554
II. Conclusions 566
References 566
Chapter 37. Gene Therapy for Patients with Head and Neck Cancer 574
I. Background 575
II. Approaches to Gene Therapy for Cancer 576
III. Genes Used in Combination Therapy 576
IV. Vectors 577
V. Gene Transfer Delivery Sites 578
VI. Gene Therapy Trials in Head and Neck Squamous Cell Carcinoma 579
VII. Future of Gene Therapy for Cancer 584
References 585
Chapter 38. Immunology and lmmunotherapy of Head and Neck Cancer 588
I. Introduction 588
II. Principles of Immunotherapy 589
III. Immune Therapeutic Strategies 590
IV. Immunology of Head and Neck Squamous Cell Carcinoma (HNSCC) 593
V. Immunotherapy of Head and Neck Cancer 595
VI. Conclusion 600
References 600
Index 612
Color Plate Section 623