Contemporary Oral Oncology Biology Epidemiology Etiology and Prevention 1st edition by Moni Abraham Kuriakose 9783319149110 3319149113

1: Carcinogenesis and Field Cancerization in Oral Squamous Cell Carcinoma

1.1 Oral Carcinogenesis

1.1.1 Clinical Progression of Oral Cancer

1.1.1.1 Potentially Malignant Lesions

1.1.2 Histological Progression

1.1.3 Molecular Model of Progression

1.1.4 Biomarkers of Oral Carcinogenesis

1.1.4.1 Tumor Suppressor Genes (TSG)

1.1.4.2 Cell Cycle and Proliferation Markers

1.1.4.3 Angiogenesis and Metastatic Markers

1.1.4.4 Cytokeratins

1.1.4.5 miRNA Markers

1.1.5 Cancer Stem Cells in Oral Carcinogenesis

1.1.6 Markers of Oral Carcinogenesis: Implications in Early Detection and Chemoprevention

1.2 Field Cancerization in Oral Cancer

1.2.1 Cellular Basis of Field Cancerization

1.2.2 Molecular Models of Field Cancerization

1.2.3 Biomarkers of Field Cancerization

1.2.3.1 TP53 Mutations

1.2.3.2 Loss of Heterozygosity

1.2.3.3 Telomerase

1.2.3.4 Ploidy Analysis

1.2.3.5 Angiogenesis Markers

1.2.3.6 Other Markers

1.2.4 Cancer Stem Cells in Field Cancerization

1.2.4.1 Implication of Field Cancerization in Diagnosis and Therapy in Oral Cancer

1.2.4.2 Definition of Terminology

References

2: Aetiology of Oral Cavity Cancer

2.1 Introduction

2.2 The Theory of Carcinogenesis (See Vol. I, Chap. 1 for Details)

2.3 Epidemiology of Oral Cancer (See Vol. I, Chap. 4 for More Details)

2.4 Oral Potentially Malignant Disorders (See Vol. I, Chap. 10 for More Details)

2.5 Clinical Presentation of OSCC and OPML

2.6 Risk Factors for OSCC

2.6.1 Tobacco

2.6.1.1 Cigarette and Cigars

2.6.1.2 Smokeless Tobacco

2.6.1.3 Waterpipe Smoking (aka Hookah, Sheesha, Shisha and Narghile)

2.6.1.4 Areca Nut/Betel Quid

2.6.2 Alcohol

2.6.2.1 Alcohol and Oral Cancer: Epidemiological Evidence

2.6.2.2 Molecular Mechanisms of the Genotoxicity of Alcohol in Relation to Oral Carcinogenesis

2.6.2.3 Acetaldehyde

2.6.2.4 DNA Adducts from Acetaldehyde

2.6.2.5 Chromosomal and DNA Damage by Acetaldehyde

2.6.2.6 Induction of CYP2E1

2.6.2.7 Oxidative Stress

2.6.2.8 Lipid Peroxidation

2.6.2.9 Enhanced Penetration of Carcinogens

2.6.3 Alcohol-Containing Mouthwashes

2.6.3.1 Alcohol-Containing Mouthwashes and Oral Cancer: Epidemiological Evidence

2.6.3.2 Alcohol-Containing Mouthwashes and Oral Cancer: Mechanistic Evidence

2.6.3.3 Unifying Hypothesis

2.6.4 Microorganisms

2.6.4.1 Human Papillomavirus

2.6.4.2 Candida

2.6.5 Diet

2.7 Immune Deficiency and Transplantation

2.8 Genetics, Syndromes and DNA Repair Defects

2.9 UV and Lip Cancer

References

3: Human Papillomaviruses and Squamous Cell Carcinomas of Head and Neck Region

3.1 HPV Genome and Proteome

3.2 Biology of HPV

3.3 Molecular Pathology of HPV Carcinogenesis

3.4 HPV-Associated Oral Diseases: Diverse Manifestations

3.5 Epidemiology of HPV in HNSCC

3.6 HPV-Associated HNC: Clinical Outcome in an Altered Entity

3.7 HPV Detection in Clinical Samples

3.8 HPV Vaccinology

3.9 Therapeutic Vaccines

3.10 Future Perspectives

References

4: Epidemiology and Site-Specific Risk Factors for Oral Cancer

4.1 Introduction and Overview

4.2 Cancer Registries

4.3 Why Collect Detailed Epidemiological Data?

4.3.1 Geographical Epidemiology

4.3.2 Differences by Sex

4.3.3 Differences by Race/Ethnicity

4.4 Age Distributions

4.5 Mortality Rates and Trends over Time

4.6 Mortality Trends by Birth Cohort and Forward Projections

4.7 Global Scenario of Oral Potentially Malignant Disorders (OPMD)

4.7.1 Global Prevalence of OPMD

4.7.2 Age and Gender Distribution of OPMD

4.7.3 Malignant Transformation of OPMD

4.8 Site-Specific Risk Factors for Oral Cancer (ICD 10, C00–C06)

4.8.1 Lip Cancer (ICD 10, C00)

4.8.2 Cancer of the Oral Tongue (C001–C002)

4.8.3 Gum Cancer (ICD 10, C03)

4.8.4 Cancers of the Floor of the Mouth (ICD 10, C04)

4.8.5 Carcinoma of the Palate (ICD 10, C05)

4.8.6 Carcinoma of the Other and Unspecified Parts of the Mouth (ICD 10, C06)

References

5: Histopathology of Oral Cavity Cancer and Potentially Malignant Disorders

5.1 Introduction

5.1.1 Pathology Practice, the Pathologist, and Surgical Pathology Report

5.1.2 Anatomic Considerations

5.1.3 Sampling Considerations

5.2 Squamous Cell Carcinoma of the Oral Cavity

5.2.1 Clinical Appearance and Microscopic Correlation

5.2.2 Diagnostic Pitfalls and Potential Issues

5.2.3 Oral Cavity Subsite-Related Tumor Characteristics

5.2.4 Pathologic Prognosticators of Oral Squamous Cell Carcinoma

5.2.4.1 Tumor Site

5.2.4.2 Tumor Size

5.2.4.3 Tumor Thickness (TT) and Depth of Invasion (DOI)

5.2.4.4 Tumor grade

5.2.4.5 Pattern of invasion (POI)

5.2.4.6 Perineural invasion

5.2.4.7 Lymphovascular Invasion

5.2.4.8 Bone invasion

5.2.4.9 Surgical Margins in Oral Cancer

5.2.4.10 Tumor lymphoid response

5.2.4.11 Stromal Desmoplastic Response (SDR)

5.2.4.12 Histologic Prognosticators: Summary

5.2.5 Squamous Cell Carcinoma Variants

5.2.5.1 Verrucous carcinoma (VC)

5.2.5.2 Papillary Squamous Cell Carcinoma (PSCC)

5.2.5.3 Basaloid Variant of Squamous Cell Carcinoma (BSCC)

5.2.5.4 Spindle Cell (Sarcomatoid) Carcinoma

5.2.5.5 Adenosquamous Carcinoma

5.2.5.6 Acantholythic Squamous Cell Carcinoma

5.2.5.7 Lymphoepithelial carcinoma

5.2.6 Pathology Considerations of Nodal Disease Assessment

5.2.7 OSCC in Specific Circumstances

5.2.7.1 Human Papillomavirus Role in Oropharyngeal Squamous Cell Carcinoma

5.2.7.2 Human Papillomavirus Role in Oral Squamous Cell Carcinoma

5.2.7.3 Squamous Cell Carcinoma in the Younger Patients

5.2.7.4 Squamous Cell Carcinoma in the Immunosuppressed Patient

5.2.8 Diagnostic Issues, Differential Considerations, and Mimics of Oral Squamous Cell Carcinoma

5.2.8.1 Oral Squamous Cell Carcinoma Versus Other Cancers

5.2.8.2 Oral Squamous Cell Carcinoma Versus Benign Diseases

5.3 Potentially Malignant Disorders and Early Oral Cancer

5.3.1 Definition

5.3.2 Synonyms

5.3.3 Epidemiology

5.3.4 Clinical and Macroscopic Aspects

5.3.5 Microscopic Aspects of Potentially Malignant Disorders

5.3.5.1 Conceptual Problems

5.3.5.2 Molecular Aspects of Oral Dysplasia

5.3.5.3 Practical Considerations

5.3.5.4 Early carcinoma

5.3.6 Oral Epithelial Dysplasia and Early Oral Cancer Diagnostic Pitfalls

5.3.7 Potentially Malignant Disorders: Summary

References

6: Emerging Cancer Biomarkers for HNSCC Detection and Therapeutic Intervention

6.1 Introduction

6.2 Cancer Biomarkers

6.3 HNSCC Biomarkers

6.4 HNSCC Genomic and Epigenetic-Derived Biomarkers

6.5 HNSCC Proteomics-Derived Biomarkers

6.6 HNSCC Salivary and Blood-Derived Biomarkers

6.7 Strategies for HNSCC Biomarker Detection

6.8 Future Perspectives on Cancer Biomarkers and Oncology Drug Development

References

7: Oral Potentially Malignant Disorders

7.1 Oral Lichen Planus

7.2 Leukoplakia

7.3 Erythroplakia

7.4 Erythroplakia with Ulceration

7.5 Proliferative Verrucous Leukoplakia

7.6 Oral Submucous Fibrosis

7.7 Management of Oral Potentially Malignant Lesions

7.8 Pathology of Oral Potentially Malignant Lesions

7.9 Treatment Options of OPML

Bibliography

8: Oral Submucous Fibrosis

8.1 Introduction

8.2 Historical Perspective

8.3 Epidemiology

8.4 Aetiology

8.5 Epidemiological Studies

8.6 Dose Response

8.7 Genetic Predisposition

8.8 Experimental Animal Studies

8.9 In Vitro Studies

8.10 Summary on Aetiology

8.11 Aetiopathogenesis

8.12 Mechanisms of Pathogenesis of Oral Submucous Fibrosis

8.12.1 Constituents of Areca Nut and Their Primary Effects

8.12.2 Fibrogenic Factors

8.12.3 Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinases (MMPs and TIM

8.12.4 Copper and Related Structural Changes of Collagen

8.12.5 Changes in the Extracellular Matrix

8.12.6 Genetic Polymorphism Predisposing to OSF

8.12.7 Clinical Features

8.12.8 Staging

8.12.9 Histopathology

8.12.10 Molecular Studies

8.12.11 Malignant Transformation

8.12.12 Molecular Events During OSF-Carcinoma Sequence

8.13 Management

References

9: Advances in Early Detection and Diagnostic Adjuncts in Oral Cavity Cancer

9.1 Introduction

9.2 Oral Potentially Malignant Disorders (OPMD)

9.2.1 Leukoplakia

9.2.2 Erythroplakia

9.2.3 Oral Lichen Planus

9.2.4 Chronic Hyperplastic Candidosis

9.3 Screening for Oral Cancer and Oral Potentially Malignant Disorders

9.4 Detection of Oral Cancer and Oral Potentially Maligant Lesions

9.4.1 Conventional Oral Examination

9.4.2 Diagnostic Adjuncts

9.4.2.1 Toluidine Blue

9.4.2.2 Reflectance Visualisation

ViziLite™ and ViziLite Plus™

Microlux/DLTM

9.4.2.3 Optical Fluorescence Imaging (Tissue Autofluorescence)

VELscopeTM

Identafi®

9.5 Narrow Band Imaging

9.5.1 Other Optical Imaging Techniques

9.5.1.1 Optical Coherence Tomography

9.5.1.2 Angle-Resolved Low-Coherence Interferometry

9.5.1.3 Raman Spectroscopy

9.5.2 Optical Molecular Imaging Using Exogenous Molecular Probes

9.5.2.1 Light-Induced Fluorescence from 5-Aminolevulinic Acid (5-ALA)

9.5.2.2 Fluorescent Glucose Metabolism

9.5.2.3 Evaluating Epidermal Growth Factor Receptor (EGFR) Expression

9.5.2.4 Aberrant Glycosylation Via Lectins

9.6 Key Points

References

10: Screening for Oral Cancer

10.1 Introduction

10.2 Screening as a Disease Control Intervention

10.3 Oral Cancer as a Suitable Disease for Screening

10.4 Objectives of Oral Cancer Screening

10.5 Oral Potentially Malignant Disorders (OPMDs)

10.6 Invasive Oral Cancer

10.7 Screening Tests for Oral Neoplasia

10.7.1 Visual Screening by Doctors and Health Workers

10.7.2 Mouth Self-Examination

10.7.3 Adjunctive Tests to Visual Screening

10.8 Biopsy and Histopathology

10.9 Evidence for Effectiveness of Oral Cancer Screening

10.10 National Oral Cancer Screening Programmes

References

11: Prevention of Oral Cancer

11.1 Introduction and Epidemiology

11.2 Pathogenesis and Risk Factors

11.2.1 Tobacco

11.2.1.1 Smoking

11.2.1.2 Smokeless Tobacco

11.2.2 Alcohol

11.2.3 Areca Nut

11.2.4 Combined Effects of Smoking, Tobacco Chewing, and Alcohol

11.2.5 Human Papillomavirus (HPV)

11.2.6 Oral Hygiene

11.2.7 Trauma

11.2.8 Genetic Disorders and Family History of Cancer

11.3 Prevention of Oral Cancer

11.3.1 Primordial Prevention

11.3.2 Primary Prevention

11.3.3 Secondary Prevention

11.3.4 Tertiary Prevention

11.4 Chemoprevention of Oral Cancer

References

12: Biologic Basis of Personalized Therapy in Head and Neck Squamous Cell Carcinoma

12.1 High-Throughput Data

12.1.1 DNA

12.1.1.1 Somatic Mutations

12.1.1.2 CNVs

12.1.1.3 Indels

12.1.1.4 Tumor Heterogeneity

12.1.1.5 HPV

12.1.2 Epigenetic Modifications

12.1.3 Transcript Level

12.1.3.1 Array-Based Profiling

12.1.3.2 RNA Sequencing

12.1.4 miRNA

12.1.5 Proteomic Profiling

12.2 Bioinformatics

12.2.1 Sample Characteristics

12.2.1.1 Quality and Quantity of DNA

12.2.1.2 Sample Purity: Normal Cell Contamination and Tumor Content

12.2.1.3 Tumor Heterogeneity

12.2.2 Processing of Sequencing Data

12.2.2.1 Alignment

12.2.2.2 Read Filtering

12.2.3 Variant Prioritization and Clinical Interpretation

12.2.3.1 Coverage and Percentage Supporting Reads

12.2.4 Annotation Against Databases

12.2.4.1 Novel Versus Known Variants

12.2.4.2 Somatic Versus Germline

12.2.4.3 Synonymous Versus Non-synonymous

12.2.4.4 Location

12.2.4.5 Pathway

12.3 Personalized Medicine

12.3.1 Expression Profiling in Head and Neck Cancer

12.3.2 The Mutational Landscape of the Tumor

12.3.3 The Role of Next-Generation Sequencing

12.3.4 Clinical Correlation

12.3.4.1 Current Therapeutic Paradigm for HNSCC

12.3.4.2 Methods for Monitoring Response and Progression of HNSCC

12.3.4.3 Challenges in the Treatment and Monitoring of HNSCC

References

13: Role of Cancer Stem Cells in Oral Cancer

13.1 Introduction

13.1.1 Cancer Stem Cell Concept in Carcinogenesis

13.1.2 Normal and Cancer Stem Cells

13.1.2.1 Self-Renewal

13.1.2.2 Proliferation

13.1.2.3 Metastasis

13.1.3 Initiation of Carcinogenesis

13.1.3.1 Stem Cell: Target of Transforming Mutation

13.1.3.2 Progenitor Cell: Target of Transforming Mutation

13.1.3.3 Dedifferentiation of a Differentiated Cell

13.1.3.4 Fusion of Tissue-Specific Stem Cells with Circulating Bone Marrow Cell

13.1.4 The Niche Concept

13.1.5 Molecular Basis/Markers of Stem Cell Transformation

13.2 Contribution of Cancer Stem Cells to Disease Progression

13.2.1 Angiogenesis

13.2.1.1 Role of Cancer Stem Cells in Angiogenesis

13.2.1.2 Vasculogenic Mimicry

13.2.2 Metastasis

13.2.2.1 Signaling Pathways Involved in Stemness Also Induce EMT

13.2.2.2 Transcriptional Regulators of EMT: A Potential Link Between Invasion and Stemness

13.2.3 Chemo-/Radioresistance

13.2.4 Tumor Heterogeneity

13.3 Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma

13.3.1 CSC Concept and Triggers for Transformation

13.3.1.1 Tumor Heterogeneity

13.3.1.2 The CSC Concept

13.3.1.3 Origin of CSCs in Head and Neck Cancer

Transformation of Adult Stem Cells

Dedifferentiation of Malignant Tumor Cells

HPV-Mediated Transformation

13.3.2 Cancer Stem Cells in Epithelial-Mesenchymal Transition and Metastases

13.3.3 Effect of the CSC Niche

13.3.4 Role in Therapy Resistance

13.3.5 CSC in Recurrent Disease and Second Primary Cancers

13.3.6 Molecular Profile of HNSCC CSCs

13.3.6.1 Markers of Cancer Stem Cell Identification and Their Clinical Relevance

CD44

CD133

ALDH1

Other Markers

13.3.6.2 Markers Associated with Treatment Resistance

ABC Family

Anti-apoptotic Markers

13.3.6.3 Markers Associated with Epithelial-Mesenchymal Transition and Metastasis

13.3.6.4 Molecular Profile in Common with the Normal Oral Stem Cells

13.4 Cancer Stem Cells and Therapy

13.4.1 Current Therapy and CSCs

13.4.2 Targeting CSCs and Its Niche

13.4.2.1 Major Strategies, Targets, and Modulators for CSC: Therapy in Cancers

Differentiation Therapy

Elimination Therapy

Combination Therapy

13.4.2.2 Targeting the Niche

13.4.3 Anti-CSC Therapy and the NSC Population

13.4.4 Prospects of CSC-Based Targeted Therapy in Head and Neck Cancer

13.4.4.1 Possible Candidates and Anti-CSC Therapy in HNSCC

13.4.4.2 Candidates for Niche Targeting in HNSCC

13.4.4.3 Other Available Modulators and Future Prospects