American Cancer Society

Atlas of
Clinical Oncology
Published
Blumgart, Fong, Jarnagin

Hepatobiliary Cancer (2001)

Cameron

Pancreatic Cancer (2001)

Carroll, Grossfeld

Prostate Cancer (2002)

Char

Tumors of the Eye and Ocular Adnexa (2001)

Clark, Duh, Jahan, Perrier

Endocrine Tumors (2003)

Eifel, Levenback

Cancer of the Female Lower Genital Tract (2001)

Ginsberg

Lung Cancer (2002)

Grossbard

Malignant Lymphomas (2001)

Ozols

Ovarian Cancer (2003)

Pollock

Soft Tissue Sarcomas (2001)

Posner, Vokes, Weichselbaum

Cancer of the Upper Gastrointestinal Tract (2001)

Prados

Brain Cancer (2001)

Shah

Cancer of the Head and Neck (2001)

Silverman

Oral Cancer (1998)

Silverman

Oral Cancer 5th Edition (2003)

Wiernik

Adult Leukemias (2001)

Willett

Cancer of Lower Gastrointestinal Tract (2001)

Winchester, Winchester

Breast Cancer (2000)

Forthcoming
Droller

Urothelial Tumors (2003)

Fuller, Seiden, Young

Uterine and Endometrial Cancer (2003)

Raghavan

Germ Cell Tumors (2003)

Richie, Steele

Kidney Tumors (2004)

Volberding

Viral and Immunological Malignancies (2004)

Yasko

Bone Tumors (2004)

American Cancer Society

Atlas of
Clinical Oncology
Editors
GLENN D. STEELE JR, MD
Geisinger Health System
THEODORE L. PHILLIPS, MD
University of California
BRUCE A. CHABNER, MD
Harvard Medical School

Managing Editor
TED S. GANSLER, MD, MBA
Director of Health Content, American Cancer Society

American Cancer Society

Atlas of
Clinical Oncology

Oral Cancer
Fifth Edition
Sol Silverman Jr., MA, DDS
Professor of Oral Medicine
University of California
School of Dentistry
San Francisco, California

2003
BC Decker Inc
Hamilton London

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Notice: The authors and publisher have made every effort to ensure that the patient care recommended herein, including choice of drugs and drug dosages, is in
accord with the accepted standard and practice at the time of publication. However, since research and regulation constantly change clinical standards, the reader
is urged to check the product information sheet included in the package of each drug, which includes recommended doses, warnings, and contraindications. This
is particularly important with new or infrequently used drugs. Any treatment regimen, particularly one involving medication, involves inherent risk that must be
weighed on a case-by-case basis against the benefits anticipated. The reader is cautioned that the purpose of this book is to inform and enlighten; the information
contained herein is not intended as, and should not be employed as, a substitute for individual diagnosis and treatment.

Dedication
This textbook, a culmination of more than 40 years of patient care and research, is dedicated to my father,
Sol Silverman Esq., my mother, Carolyn Stern Silverman, and my wife, Betty Walden Silverman, for their
continual, uncompromising, devoted support for my work in cancer over the span of my professional career.

Contents
Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
1

Epidemiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Sol Silverman Jr., MA, DDS

2

Etiology and Predisposing Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Sol Silverman Jr., MA, DDS, Craig S. Miller, DMD, MS, Joan S. Thompson, PhD, RD, CD
3

Leukoplakia and Erythroplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Sol Silverman Jr., MA, DDS

4

Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

Sol Silverman Jr., MA, DDS, Nancy J. Fischbein, MD, William P. Dillon, MD
5

Spread of Tumor, Staging, and Survival . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

Sol Silverman Jr., MA, DDS, Nancy Lee, MD, Alan M. Kramer, MD, Richard C. K. Jordan, DDS, PhD
6

Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

Mark I. Singer, MD, FACS, Jeanne M. Quivey, MD, Theodore L. Phillips, MD,
Alan M. Kramer, MD, Sol Silverman Jr., MA, DDS
7

Complications of Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113

Sol Silverman Jr., MA, DDS

8

Restoration of Palate, Tongue, Mandible, and Facial Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

John Beumer III, DDS, MS, Ian M. Zlotolow, DMD, Arun B. Sharma, BDS, MSc
9

Leukemia and Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152

Mark M. Schubert, DDS, MSD, Douglas E. Peterson, DMD, PhD, Sol Silverman Jr., MA, DDS
10

Malignant Salivary Gland Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174

Joseph A. Regezi, MS, DDS, Sol Silverman Jr., MA, DDS, David W. Eisele, MD
11

Other Malignancies and Oral Oncology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183

Sol Silverman Jr., MA, DDS, Nancy Lee, MD, Joseph A. Regezi, MS, DDS,
Catherine M. Flaitz, DDS, MS, Michael J. Kaplan, MD, Herbert Dedo, MD
12

Human Immunodeficiency VirusAssociated Oral Malignancies. . . . . . . . . . . . . . . . . . . . . . . . . . . 200

Catherine M. Flaitz, DDS, MS, Sol Silverman Jr., MA, DDS

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210

Acknowledgment
Sincere appreciation is expressed to the contributing authors whose acknowledged expertise and contributions have made this text an authoritative, state-of-the-art publication and to Priscilla Mayer whose dedicated
work with computer processing and editing supported the high-quality product.

Preface
All multicellular animals, and certainly all vertebrates,
can develop cancer. The ability to develop cancer is a
characteristic of all cells that are capable of reproduction and growth. Cancer, by its very naturean abnormal, seemingly unrestricted growth of body cellsis
distinguished from other forms of illness.
There are many differences in the occurrence of
cancer types and sites among human populations: for
example, the high incidence of nasopharyngeal cancer
among the Chinese compared with other ethnic groups
and the low incidence of skin cancer among blacks
compared with whites.
Although cancer may occur at any age, it is preponderantly a disease of aging and can be both acute
and chronic in its course. More than half of all cancers
in the United States occur in persons over the age of 65
years. In this age group, the incidence is 2,261 cases
per 100,000 population! Many types of cancer are perceptible only when they are extensive or involve organs
difficult to treat, and others may be detected early,
treated, and cured.
This complex disease, which is a major cause of
morbidity and disability, is second only to heart disease as the leading cause of death among Americans.
Approximately one in every three Americans will have
cancer in his or her lifetime, and about one in every
four deaths is attributable to a malignant tumor.
In the United States, oral cancer accounts for nearly
3% of all cancers and approximately 2% of all cancer
deaths. Mortality is high, with 5-year survival rates
that approximate only a little more than 50%, in spite
of modern treatments that include surgery, radiation,
and chemotherapy. However, early detection of mouth
cancers (ie, when lesions are less than 3 cm in size and
show no evidence of deep invasion or metastasis) dramatically increases the survival rates. Unfortunately,
over the past decade there have been only small
improvements in early diagnosis of oral cancer: more

than 60% of all oral cancers are extensive, late-stage

malignancies at the time of diagnosis. Hence, treatment is more aggressive in trying to improve cure
rates. This approach, which increases complications of
treatments, results in only a slight improvement in survival rates. Therefore, early diagnosis of a lesion during the localized stage, combined with adequate treatment, appears to be the most effective way to further
improve oral cancer control.
Recent studies indicate that only a small number of
Americans report having been examined for oral cancer. The data varied according to demographic characteristics and the education of the patients, as well as the
training and office routines of both the dentists and the
physicians. Thus, professional and public education
programs are critical in emphasizing the need for routine oral cancer examinations, in addition to teaching
the recognition of early signs and symptoms of malignancy. Furthermore, as our knowledge of cancer
rapidly increases in the areas of oncogenes, viruses,
cellular growth and suppressor factors, and nutritional
support, a dramatic reduction in morbidity and mortality and even prevention seem to be realistic goals.
The increased risks arising from the use of tobacco
and alcohol are recognized, and more effective cessation programs are being developed. Biomarkers that
reflect abnormal cell components are being studied to
improve the control and prediction of tissue behavior.
Optimal cancer control calls for a diversity of
approaches among many health professionals, including prevention programs and diagnostic techniques.
The dental profession shares an important responsibility in the management of oral cancer, from diagnosis
through rehabilitation. Dentists have a unique opportunity in the routine mouth examination to detect
malignant neoplasms while they are still asymptomatic,
innocuous, and unsuspected. In addition, the dentist is
most often the first clinician consulted for general oral

ix

ORAL CANCER

complaints and, therefore, has the initial responsibility

of differentiating benign from precancerous and
malignant conditions. Furthermore, other health care
providers can serve the same purpose by incorporating
oral examinations in their procedures, particularly in
high-risk individuals, for example, individuals beyond
middle age who also smoke and consume alcohol.
Treatment of oral cancer often produces certain
dysfunctions and distortions in speech, appearance,
mastication, swallowing, saliva flow and consistency,
emotional stability, and dental health. Therefore,
rehabilitation becomes a major consideration in
patient management.
In preparing for their participation in cancer control, health professionals must acquire knowledge of
the biologic and epidemiologic aspects of cancer and
its prevention, early detection, diagnosis, treatment,
and rehabilitation, as well as an understanding of the
psychosocial and economic aspects of the disease. The
complexities of optimal diagnosis, management, and
control require multidisciplinary teams.
This fifth edition of Oral Cancer updates the entire
problem of oral cancer control: occurrence, etiology,
premalignant factors and prevention, diagnosis, treatment, rehabilitation, and survival. It is written in a
manner that should serve all clinicians and health professionals as a unique reference that contains both an
updated and detailed text along with a generous number of colored figures that additionally provide a colored atlas flavor.
The first eight chapters focus mainly on squamous
cell carcinoma because it is by far the most common
type of oral cancer. In Chapter 2, epidemiology, demographics, and etiology have been updated and
expanded to reflect current trends and status. The role
of tobacco, nutritional considerations, and viral
aspects have been substantially increased to reflect
their importance in neoplastic predisposition and risks.
The chapter on precancerous oral lesions has been
enlarged in both text and figures because of problems
in recognizing these lesions (primarily leukoplakias) at
risk for malignant transformation. Imaging techniques
in Chapter 4 have been expanded significantly in both
text and visual images because of their roles in diagnosis, staging, and treatment plans. Treatment has also
been enlarged to reflect current attempts in improving
survival, which also risk increasing morbidity and oral
complications of treatment. Because of problems in
survival and quality-of-life issues, material on chemo-

prevention, modern molecular analysis, and adverse

effects of cancer treatments have been substantially
expanded. Maxillofacial rehabilitation has progressed
dramatically, resulting from advances in patient care
and research; therefore, Chapter 8, Restoration of
Palate, Tongue, Mandible, and Facial Defects, has
been updated with additional text, tables, and figures.
The etiology, diagnosis, and management of other
cancers that involve oral health care providers are covered in the following four chapters. The leukemias and
lymphomas have been described by text and illustrations in Chapter 9. These malignancies are treated primarily with immunosuppressive and toxic chemotherapeutic agents that incur oral manifestations requiring
special dental management. Chapter 10 covers major
and minor salivary gland tumors and emphasizes the
special approach needed for the diagnosis and treatment of each type of gland. Sarcomas and other malignancies that affect the jaw bones and sinuses, skin cancers, nasopharyngeal and laryngeal malignancies,
melanomas, and pediatric oncology are included in
Chapter 11 to complete the overview of head and neck
cancers and clinical considerations. Even though
malignant melanomas are rare, they are covered in
detail because of their poor prognosis and difficulties
in differential diagnoses, which include ethnic pigmentation, amalgam tattoos, and focal melanosis. The
overview of pediatric oncology citing oral/dental
implications has been given attention because of the
need to rule out malignancy and management
approaches when children present with oral lesions.
Human immunodeficiency virus (HIV) infection continues to increase worldwide, with no end in sight.
HIV-associated oral malignancies, a major cause of
morbidity and mortality in this group, constitute the
last chapter. The generous colored illustrations effectively supplement the text, enhancing visual comprehension and practical applications.
In summary, this updated and expanded fifth edition of Oral Cancer should serve as a reservoir of both
written and visual information to enhance the clinicians role in the prevention, recognition, diagnosis,
management, and rehabilitation of malignancies that
affect oral and paraoral sites. In turn, this educational
resource should aid in reducing the morbidity and mortality associated with cancer.
Sol Silverman Jr., MA, DDS
December 2002

Contributors
JOHN BEUMER III, DDS, MS
Professor
UCLA Department of Dentistry
Los Angeles, California
HERBERT DEDO, MD
Professor and Vice Chairman
Department of Otolaryngology
University of California, San Francisco
San Francisco, California
WILLIAM P. DILLON, MD
Professor
Radiology, Neurology, and Neurological Surgery
Chief of Neuroradiology
Vice Chair
Department of Radiology
University of California, San Francisco
San Francisco, California
DAVID W. EISELE, MD
Professor and Chairman
Otolaryngology Head and Neck Surgery
University of California, San Francisco
San Francisco, California
NANCY J. FISCHBEIN, MD
Assistant Professor in Residence
Department of Radiology
University of California, San Francisco
San Francisco, California
CATHERINE M. FLAITZ, DDS, MS
Interim Dean and Professor
The University of Texas Dental Branch at Houston
Department of Diagnostic Sciences
Oral and Maxillofacial Pathology
Houston, Texas

RICHARD C. K. JORDAN, DDS, PHD

Associate Professor
Department of Stomatology and Pathology
University of California, San Francisco
San Francisco, California
MICHAEL J. KAPLAN, MD
Associate Professor
Otolaryngology Head and Neck Surgery
University of California, San Francisco
San Francisco, California
ALAN M. KRAMER, MD
Associate Clinical Professor of Medicine
University of California, San Francisco
San Francisco, California
NANCY LEE, MD
Assistant Professor
Department of Radiation Oncology
University of California, San Francisco
San Francisco, California
CRAIG S. MILLER, DMD, MS
Professor of Oral Medicine
University of Kentucky College of Dentistry
Department of Oral Health Practice, Oral Medicine
Lexington, Kentucky
DOUGLAS E. PETERSON, DMD, PHD
Professor and Department Chair
University of Connecticut Health Center
Farmington, Connecticut
THEODORE L. PHILLIPS, MD
Professor
Department of Radiation Oncology
University of California, San Francisco
San Francisco, California
xi

xii

ORAL CANCER

JEANNE M. QUIVEY, MD
Professor
Department of Radiation Oncology
University of California, San Francisco
San Francisco, California

SOL SILVERMAN JR., MA, DDS

Professor of Oral Medicine
School of Dentistry
University of California, San Francisco
San Francisco, California

JOSEPH A. REGEZI, MS, DDS

Professor of Oral Pathology
School of Dentistry
University of California, San Francisco
San Francisco, California

MARK I. SINGER, MD, FACS

Professor
Otolaryngology Head and Neck Surgery
University of California, San Francisco
San Francisco, California

MARK M. SCHUBERT, DDS, MSD

Professor
Department of Oral Medicine
University of Washington
Seattle, Washington

JOAN S. THOMPSON, PHD, RD, CD

Associate Professor of Nutrition
Department of Health Promotion and
Human Performance
College of Education
Weber State University
Ogden, Utah

ARUN B. SHARMA, BDS, MSC

Assistant Clinical Professor
School of Dentistry
University of California, San Francisco
San Francisco, California

IAN M. ZLOTOLOW, DMD

Chief
Dental Service
Memorial Sloan-Kettering Cancer Center
Department of Surgery
New York, New York