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Oral and Oropharyngeal Cancer
Second Edition
Oral and Oropharyngeal Cancer
Second Edition
Jatin P. Shah, MD, MS (Surg), PhD (Hon),

DSc (Hon), FACS, FRCS (Hon), FDSRCS (Hon),
FRCSDS (Hon), FRCSI (Hon), FRACS (Hon)
Professor of Surgery, Weil Cornell Medical College
and
E W Strong Chair in Head and Neck Oncology
Memorial Sloan Kettering Cancer Center
New York, USA
Newell W. Johnson, CMG, FMedSci, MDSc, PhD,

FDSRCS (Eng), FRACDS, FRCPath (UK),
FFOP (RCPA), FOMAA, FHEA (UK), FICD
Honorary Professor of Dental Research, Menzies Health Institute Queensland
and
School of Dentistry and Oral Health, Griffith University
and
Emeritus Professor, Griffith Institute for Educational Research
Queensland, Australia
and
Emeritus Professor of Oral Health Sciences
King’s College London
London, United Kingdom
CRC Press
Taylor & Francis Group
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© 2019 by Taylor & Francis Group, LLC

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Library of Congress Cataloging-in-Publication Data
Names: Shah, Jatin P., editor. | Johnson, Newell W., editor.

Title: Oral and oropharyngeal cancer / [edited by] Jatin P. Shah, Newell W. Johnson.
Description: Second edition. | Boca Raton, FL : CRC Press, 2018. | Preceded by Oral cancer / edited by Jatin P. Shah,
Newell W. Johnson, John G. Batsakis. 2003. | Includes bibliographical references.
Identifiers: LCCN 2017048943 (print) | LCCN 2017050075 (ebook) | ISBN 9781351138543 (eBook General) |
ISBN 9781498700092 (eBook PDF) | ISBN 9781498715942 (eBook ePub3) | ISBN 9781498700085 (hardback : alk. paper)
Subjects: | MESH: Mouth Neoplasms | Oropharyngeal Neoplasms
Classification: LCC RC280.M6 (ebook) | LCC RC280.M6 (print) | NLM WU 280 | DDC 616.99/431--dc23
LC record available at https://lccn.loc.gov/2017048943
Visit the Taylor & Francis Web site at

http://www.taylorandfrancis.com
and the CRC Press Web site at
http://www.crcpress.com
Contents
Preface to the second edition vii

Contributors ix
Part I PATHOLOGY AND BIOLOGY 1
1 Global epidemiology 3
Newell W. Johnson and Hemantha Amarasinghe
2 Etiology and risk factors 19
Newell W. Johnson, Bhawna Gupta, David J. Speicher, Cecily S. Ray, Mushfiq Hassan Shaikh,
Nezar al-Hebshi, and Prakash C. Gupta
3 Clinical features and diagnosis 95
Camile S. Farah, Maryam Jessri, Keziah John, Yastira Lalla, An Vu, and Omar Kujan
4 Histopathology 167
Paul M. Speight
5 Molecular pathology 205
Rifat Hasina, Nishant Agrawal, and Mark W. Lingen
Part II CLINICAL MANAGEMENT 233
6 Clinical evaluation and differential diagnosis 235

Laura Wang and Jatin P. Shah
7 Workup and staging 255
8 Factors affecting choice of treatment 265
9 Management of potentially malignant disorders of the mouth and oropharynx 273
Rachel A. Giese, Jay O. Boyle, and Jatin P. Shah
10 Cervical lymph nodes 287
Aviram Mizrachi and Jatin P. Shah
11 Surgical approaches to oral cavity and oropharynx 321
Pablo H. Montero and Jatin P. Shah
12 Radiotherapy 369
Sean McBride
13 Chemotherapy 383
Andres Lopez-Albaitero and Matthew G. Fury
14 Complications of surgical treatment and their management 389
Pablo H. Montero, Jatin P. Shah, and Bhuvanesh Singh
15 Reconstructive surgery: Soft tissue 399
Adrian Sjarif and Evan Matros
16 Reconstructive surgery: Mandible 411
Ivana Petrovic, Colleen McCarthy, and Jatin P. Shah
v
vi Contents
17 Reconstructive surgery: Maxilla 425

Ralph W. Gilbert
18 Palliative care for head and neck cancer 431
Catriona R. Mayland and Simon N. Rogers
Part III OUTCOMES AND FOLLOW-UP 439
19 Oncologic outcomes 441

Pablo H. Montero, Jocelyn C. Migliacci, and Snehal G. Patel
20 Functional outcomes and rehabilitation 457
Jocelyn C. Migliacci, Allison J. Kobren, and Snehal G. Patel
21 Prognostic nomograms 465
Pablo H. Montero, Jocelyn C. Migliacci, and Snehal G. Patel
22 Prosthetic restoration and rehabilitation 479
Ivana Petrovic, George Bohle, and Jatin P. Shah
23 Prevention of oral and oropharyngeal cancer 499
Newell W. Johnson, Mushfiq Hassan Shaikh, Nigel Alan John McMillan,
Pankaj Chaturvedi, and Saman Warnakulasuriya
Index 539
Preface to the second edition
Since the first edition of this textbook was published in Surgical approaches to the treatment of primary lesions
2003, many changes in epidemiology and in management and regional lymph node metastases, whether “conven-
have occurred. Oral cancer—predominantly squamous tional” open surgery or increasingly with robotics, have
cell carcinomas affecting the lips, intraoral tongue and the made great strides. Primary radiotherapy, adjuvant radio-
mucosae of the oral cavity—remains in the top ten malig- therapy and/or cytotoxic chemotherapy regimens continue
nancies that afflict humankind. Indeed, in many regions, to be refined. Most strikingly, biologic therapies, particu-
such as south Asia and Melanesia, it can be the most com- larly immunotherapeutic therapies, have blossomed. This
mon malignancy amongst males, perhaps sixth in women, has brought head and neck cancer treatment firmly into the
often second overall. These remain predominantly due to age of personalized medicine. Many drugs and antibodies
tobacco use—both smoked and smokeless, the latter often can diminish the effects of mutant genes in cancer cells and
in combination with areca (betel) nut, together with alcohol should be restricted to patients whose neoplasm expresses
abuse, in a background of diets deficient in antioxidant vita- such mutations. Some neoplasms have molecular changes
mins and minerals. They are predominantly diseases of the that block the body’s natural defenses and agents are avail-
deprived, though no socioeconomic group is immune. They able that can reactivate the natural killer immune response
continue to be a major public health and personal problem of cell-mediated immunity. Many new drugs are becoming
globally. Indeed, the burden of disease is rising, partly due available and being licensed in many countries for a range
to population growth and aging populations in the high- of malignancies. Dramatic results are being shown, but
risk communities. most of these approaches remain not fully proven, so rou-
Management of oral cancer has improved considerably tine use should perhaps wait for the results of good-quality
in terms of survival rates and quality of life over the decade clinical trials.
and a half since we wrote the first edition, but this only Surgical ablation and reconstruction techniques have
applies to advanced multidisciplinary treatment centers, improved continuously. However, a high proportion of our
and most of these are in the developed countries. Many low- patients still die with or of their cancer, so that we have again
and middle-income countries still lack resources for early included a chapter on palliative care. Primary prevention
detection and effective treatment, though some are models through public education and health promotion, secondary
of primary prevention through public education and some- prevention through screening where appropriate and early
times screening programs. detection remain central to control of head and neck cancer.
Unfortunately, as the incidence rates of tobacco and So this second edition has the same philosophical breadth
alcohol-related cancers have begun to decline in some coun- as before, with extension to the oropharynx.
tries, the world has been swept by an epidemic of cancers of We wish to recognize the contributors to the first edition
the oropharynx, and sometimes the mouth and hypophar- who are not represented this time. Especially we pay tribute
ynx, associated with oncogenic types of the human papil- to the late Professor John Batsakis, whose pre-eminence as
lomavirus (HPV) family. These are the same viruses that a histopathologist contributed so much to the first edition.
cause over 90% of cancers of the uterine cervix and anal We welcome new authors who have filled the gaps he left
and penile cancers in men who have sex with men. These so ably and who have added new depth to the chapters on
genital cancers and HPV-positive head and neck cancers are diagnosis, pathology and molecular biology. Many of our
regarded today as sexually transmitted diseases. Fortunately, colleagues have joined us in expanding and improving
HPV-driven head and neck cancers respond relatively well chapters for which we have remained primarily responsible.
to treatment, so that radiotherapeutic (with or without adju- We thank them all for enhancing the quality of this edition.
vant chemotherapy) regimes can be de-escalated. Because of
these dramatic changes, we have enlarged the book to cover Jatin P. Shah and Newell W. Johnson
cancers of the oropharynx as well as oral cancers. New York, London and Brisbane, November 2017
vii
Contributors
Nishant Agrawal, MD Rachel A. Giese, MD

Department of Surgery Department of Head and Neck Surgery
University of Chicago Memorial Sloan Kettering Cancer Center
Chicago, Illinois New York City, New York
Nezar al-Hebshi, BDS, PhD Ralph W. Gilbert, MD, FRCSC

Kornberg School of Dentistry Gullane/O’Neil Chair in Otolaryngology/H&N
Temple University Surgery
Philadelphia, Pennsylvania University Health Network
University of Toronto
Hemantha Amarasinghe, BDS, MSc, MD
Toronto, Canada
Cancer Epidemiologist and Consultant in
Community Dentistry Bhawna Gupta, PhD, MIPH, BDS
Institute of Oral health Menzies Health Institute
Maharagama, Sri Lanka and
George C Bohle III, DDS School of Dentistry and Oral Health
The Dental Depot Griffith University
Oklahoma Queensland, Australia
Jay O. Boyle, MD Prakash C. Gupta, DSc

Head and Neck Service Healis–Sekhsaria Institute For Public Health
Memorial Sloan Kettering Cancer Center Navi Mumbai, India
New York City, New York Rifat Hasina, DDS, PhD
Pankaj Chaturvedi, MS, MNAMS, FICS, FAIS, FACS, PDCR Department of Surgery
Department of Head Neck Surgery University of Chicago
Tata Memorial Hospital Chicago, Illinois
Mumbai, India
Maryam Jessri, DDS, PhD
Camile S. Farah, BDSc, MDSc, PhD, FRACDS (OralMed), FOMAA, Australian Centre for Oral Oncology Research &
FIAOO, FICD, FPFA Education
Australian Centre for Oral Oncology Research & UWA Dental School
Education The University of Western Australia
UWA Dental School Perth, Australia
The University of Western Australia
Keziah John, BDSc, MPhil
Perth, Australia
Australian Centre for Oral Oncology Research &
Matthew G. Fury, MD PhD Education
Department of Medicine UWA Dental School
Memorial Sloan Kettering Cancer Center The University of Western Australia
New York City, New York Perth, Australia
ix
x Contributors
Newell W. Johnson, CMG, FMedSci, MDSc, PhD, FDSRCS (Eng), Sean McBride, MD, MPH
FRACDS, FRCPath (UK), FFOP (RCPA), FOMAA, FHEA (UK), FICD Memorial Sloan Kettering Cancer Center
Honorary Professor of Dental Research New York
Menzies Health Institute Queensland
Colleen McCarthy, MD, FRCS(C)
and
School of Dentistry and Oral Health
New York
Griffith University
and Nigel Alan John McMillan, BSc, PhD
Emeritus Professor Director, Understanding Chronic Conditions
Griffith Institute for Educational Research Program
Queensland, Australia Menzies Health Institute
and
and
School of Medical Sciences
Emeritus Professor of Oral Health Sciences Griffith University
King’s College London Queensland, Australia
London, United Kingdom
Jocelyn C. Migliacci
Allison J. Kobren, MS, CCC-SL
Department of Surgery
Head and Neck Service
Speech-Language Pathology
NYU Langone Health at Bellvue Hospital Center
New York City, New York
Omar Kujan, DDS, PhD Aviram Mizrachi, MD
Australian Centre for Oral Oncology Research & Education Attending Surgeon
UWA Dental School Department of Otorhinolaryngology Head and Neck
The University of Western Australia Surgery
Perth, Australia Rabin Medical Center
Director, Center for Translational Research in Head and
Yastira Lalla, BDSc, MPhil
Neck Cancer
Australian Centre for Oral Oncology Research & Education
Davidoff Cancer Center
UWA Dental School
Israel
Perth, Australia Pablo H. Montero, MD
Research Associate, Head and
Mark W. Lingen, DDS, PhD, FRCPath
Neck Service
Department of Pathology
University of Chicago
Chicago, Illinois
Andres Lopez-Albaitero, MD
Ear Nose and Throat Associates of New York and
and Attending Surgeon, Head and Neck Surgery
Assistant Clinical Professor Department of Surgery
Mount Sinai School of Medicine Clínica Las Condes
New York City, New York Santiago, Chile
Evan Matros, MD, MMSc, MPH Snehal G. Patel, MD, FRCS
Plastic and Reconstructive Surgical Service Department of Surgery
Memorial Sloan Kettering Cancer Center Head and Neck Service
New York City, New York Memorial Sloan Kettering Cancer Center
Catriona R. Mayland, MBChB, MD, FRCPS (Glas) New York City, New York
Palliative Care Institute
Ivana Petrovic, MD, PhD
University of Liverpool
and
New York
Academic Department of Palliative and
End-of-life Care Cecily S. Ray, MPH
Royal Liverpool University Hospital Healis–Sekhsaria Institute For Public Health
Liverpool, United Kingdom Navi Mumbai, India
Contributors xi
Simon N. Rogers, MD, FRCS (Eng), FRCS (Maxfac) Adrian Sjarif, MBBS (Hons), BSc, MS, FRACS
Evidence-Based Practice Research Centre Department of Plastic and Reconstructive Surgery
Faculty of Health and Social Care St. George Hospital
Edge Hill University Sydney, Australia
Omskirk, United Kingdom David J. Speicher
and Menzies Health Institute
and
Regional Maxillofacial Unit
School of Dentistry and Oral Health
Aintree University Hospitals NHS Trust
Griffith University
Liverpool, United Kingdom
Jatin P. Shah, MD, MS (Surg), PhD (Hon), DSc (Hon), FACS, FRCS (Hon), Paul M. Speight, BDS, PhD, FDSRCPS, FDSRCS (Eng), FDSRCS(Ed), FRCPath
FDSRCS (Hon), FRCSDS (Hon), FRCSI (Hon), FRACS (Hon) School of Clinical Dentistry
Professor of Surgery University of Sheffield
Weil Cornell Medical College Sheffield, United Kingdom
and
An Vu, BDSc, MPhil
E W Strong Chair in Head and Neck Oncology
Australian Centre for Oral Oncology Research & Education
UWA Dental School
Mushfiq Hassan Shaikh, BDS, MSc, PhD Perth, Australia
Menzies Health Institute Laura Wang, MBBS, MS
and Liverpool Hospital
School of Dentistry and Oral Health Sydney, Australia
Griffith University
Saman Warnakulasuriya, MDSc (Melb), PhD (Bristol), FDSRCS (Eng),
FRACDS, FRCPath (UK), FFOP (RCPA), FICD, FILT, FMedSci
Bhuvanesh Singh, MD, PhD, FACS Dental Institute
Memorial Sloan Kettering Cancer Center King’s College
New York London, United Kingdom
I
Part
Pathology and biology
1 Global epidemiology 3
Newell W. Johnson and Hemantha Amarasinghe
2 Etiology and risk factors 19
Newell W. Johnson, Bhawna Gupta, David J. Speicher, Cecily S. Ray, Mushfiq Hassan Shaikh,
Nezar al-Hebshi, and Prakash C. Gupta
3 Clinical features and diagnosis 95
Camile S. Farah, Maryam Jessri, Keziah John, Yastira Lalla, An Vu, and Omar Kujan
4 Histopathology 167
Paul M. Speight
5 Molecular pathology 205
Rifat Hasina, Nishant Agrawal, and Mark W. Lingen
1
Global epidemiology
NEWELL W. JOHNSON AND HEMANTHA AMARASINGHE
Definitions of oral cancer 3 Global scenario of oral potentially malignant

Incidence rates worldwide 5 disorders (OPMD) and laryngeal leukoplakia 14
Differences by sex 5 Global prevalence of OPMD 14
Age distributions 7 Age and gender distribution of OPMD 16
Ethnic variations 9 Malignant transformation of OPMD 16
Mortality rates and trends 11 References 16
and 2011, apart from lesions of the salivary glands, gingivae,

DEFINITIONS OF ORAL CANCER nasopharynx, nasal cavity and sinuses, more than 95% were
squamous cell carcinomas. The increasing number of can-
Malignant neoplasms are major causes of fear, morbidity cers associated with Human Papillomaviruses, mostly in the
and mortality all over the world. Cancer is one of the five oropharynx, have a more basaloid, non-keratinising mor-
main causes of death in all societies, with its relative posi- phology. Neverthless “upper aerodigestive tract alcohol- and
tion v arying with age and sex. Figure 1.1 shows the main tobacco-related oral squamous cell carcinomas” remain the
causes of death in England and Wales in 2014, as a typical major head and neck cancers. They represent a major global
example of Western industrialized countries (1). In devel- public health problem and constitute the major workload of
oping countries the proportions will differ, with infectious head and neck oncologists worldwide. Our emphasis is thus
diseases being a larger component and cardiovascular dis- on mucosal disease. Because cancers in these sites, especially
ease a smaller component. Cancer numbers are important, in the mouth, often arise out of long-standing, potentially
however. In England and Wales, for example, in the past malignant disorders (earlier called lesions and conditions),
65 years infections have declined as a major cause (in spite these are given due consideration; less extensive coverage is
of the HIV epidemic) so that diseases of the heart and cir- given to other lesions.
culatory system now dominate in men, with cancer second; Most of the international databases employ the Inter
however, cancer dominates in women, especially in the national Classification of Diseases (ICD) coding system of
third to sixth decades of life. Globally, “oral cancer” is the the World Health Organization (WHO), and most of the
sixth most common cause of cancer-related death, although data currently available are expressed according to the tenth
many people are unaware of its existence. revision of this system (ICD-10). It is particularly impor-
This text deals with malignant neoplasms affecting the tant to define these codes and to be clear how many of these
oral cavity, principally the oral mucosa, and the orophar- precise anatomic sites are included in any particular data-
ynx. These diseases have much in common with squamous set under study. Neoplasms of the major salivary glands
cell carcinomas arising elsewhere in the upper aerodiges- clearly have quite distinct natural histories, ill-understood
tive tract, which share common risk factors, so studies of etiologies and distinct management protocols compared
“head and neck cancer” are frequently drawn upon when with mucosal cancers. Similarly, nasopharyngeal malig-
issues relevant to oral cancer are discussed. Of these can- nancies are usually Epstein–Barr virus-related carcinomas
cers, the vast majority are squamous cell carcinomas arising that differ distinctly from the more widespread alcohol- and
in the mucous membranes of the mouth and the pharynx. tobacco-related squamous cell carcinomas of the rest of the
Indeed, of all the oropharyngeal malignancies reported to upper aerodigestive tract. Datasets should be examined
the Surveillance, Epidemiology and End Results program carefully to determine whether the major salivary glands
of the National Cancer Institute of the United States Public and nasopharynx are included, as they so often are (ICD
Health Service (SEER) registries in the USA between 1975 codes C07–08 and C11). Many datasets make a distinction
3
(b)
(a)
4 Global epidemiology
–
5000
10,000
15,000
20,000
25,000
30,000
35,000
40,000
0
5000
10,000
15,000
20,000
25,000
30,000
35,000
Ischaemic heart diseases
Dementia and Alzheimer disease Dementia and Alzheimer disease

Malignant neoplasm of trachea,
Ischaemic heart diseases bronchus and lung
Cerebrovascular diseases Chronic lower respiratory diseases
Cerebrovascular diseases
Chronic lower respiratory diseases
Influenza and pneumonia
Influenza and pneumonia
Malignant neoplasm of prostate
Malignant neoplasm of trachea, bronchus and lung
Malignant neoplasm of colon, sigmoid,
Malignant neoplasms of female breast rectum and anus
Malignant neoplasms, stated or presumed to primary
Malignant neoplasm of colon, sigmoid, of lymphoid, haematopoietic and related tissue
rectum and anus
Diseases of liver
Diseases of the urinary system
Malignant neoplasms, stated or presumed to primary of

lymphoid, haematopoietic and related tissue
registered
Number of deaths
registered
Figure 1.1 Categorization of the major causes of death in England and Wales in 2014. (a) Males; (b) females.
Number of deaths
Incidence rates worldwide / Differences by sex 5
between lip and intraoral cancer and we have to be clear the most common site and accounted for about a third of
whether oral cancer is taken to include the oropharynx and all cancers; it is still the most common cancer among men
hypopharynx in any given dataset. In this second edition in Sri Lanka (3–5). The proportion is falling, partly due
we have added consideration of cancers of the oropharynx to increased detection of other cancers by more extensive
and of the hypopharynx, because of the global epidemic screening programs and improved techniques (5). Even
of Human Papillomavirus-related cancers of these sites within the subcontinent, there are striking differences in
(ICD-10 codes C01, C09, C10 and, less often, C12 and C13). incidence rates. The highest rate for tongue and mouth can-
cers is reported for men living in South Karachi, Pakistan;
the second highest is from Trivandrum city in Kerala, India.
Extremely high rates for women are seen in the Tamil com-
INCIDENCE RATES WORLDWIDE munity in Malaysia—higher even than in Tamil Nadu itself:
upper aerodigestive tract sites in Indian females in peninsu-
The databases from which these estimates are derived are far lar Malaysia are the second most common cancers, behind
from ideal: many parts of the world produce no data at all, in breast and above uterine cervix (6).
others (often among the most populous), the data may come According to GLOBOCAN 2012 data, the highest inci-
from localized, atypical regions. Hospital-based cancer reg- dence of oral cancers (ICD C00–C08) is found in Melanesia
istries naturally gather biased information—those cases that (astounding rates of 22.9 per 100,000 in men and 16.0 per
present to hospital only; thus, in many developing countries, 100,000 in women, though there are caveats about the quality
cases may not come to attention at all, either because of fear of these data) (2). In India alone, over 100,000 cases of oral
or the inability of poor people to access hospital services. cancer are registered every year and the numbers are rising.
This is certainly true of incidence data. Death rates may be Though men predominate overall, among females a very high
even more unreliable because, in many developing countries, incidence is found throughout south central Asia (4.7 per
follow-up even of treated cases is impossible. Death certifica- 100,000). In terms of countries, Maldives and Sri Lanka have
tion is not always compulsory and there is limited interna- the highest incidence of oral cancer in the south Asian region.
tional standardization in the categories of cause of death, let Poor access to health services contributes to high mortality.
alone calibration of those signing death certificates.
Figure 1.2 plots the estimated numbers of new cases DIFFERENCES BY SEX
of most common cancers by anatomic site in male and in
female patients. There are striking differences. As already noted, worldwide, the incidence of oral and pha-
For 2012, GLOBOCAN estimates indicate that there ryngeal cancers overall is higher for males than females.
were 9.1 million new cases of cancer and 4.4 million cancer According to the International Agency for Research on
deaths for those between the age of 0 and 69 years. Lung Cancer (2), the age-specific incidence of “oral cavity” and
cancer is the leading cancer among men and breast cancer “other pharynx” cancers was 5.5 and 3.2 per 100,000 popu-
is the most common cancer among women (2). lation for males in 2012 and 2.5 and 0.7 for females, respec-
According to the GLOBOCAN 2012 data, for both tively (see Table 1.1). This may be because of their greater
sexes, combined cancer of the lip and oral cavity (ICD-10 indulgence in the most important risk factors, such as
COO-CO6), excluding hypo-, oro-, and naso-pharynx) heavy alcohol and tobacco consumption for intra-oral can-
ranks ninth overall, behind lung, breast, colon and rectum, cer and sunlight for lip cancer in those who work outdoors.
prostate, stomach, liver, cervix uteri and esophagus, in that However, oral cancer in females is increasing in some parts
order. When considering oral and pharyngeal cancer, the of the world. For instance, a study from Argentina showed
annual estimated incidence is around 300,373 cases for lip the male:female ratio to be 1.24:1 for the period 1992–2000
and oral cavity (ICD-10: C00–08) and 142,378 for “other” compared to 7.1:1 for the 1950–1970 period (7). The inci-
pharyngeal cancers (C09–C10, C12–14) i.e: excluding the dence of tongue and other intra-oral cancers for women can
nasopharynx because of its different aetiology and biology: be greater than or equal to that for men in high-incidence
two-thirds of these cases occurring in developing countries areas such as India, where betel quid/areca nut chewing (and
(2). Figure 1.3 shows the incidence and mortality due to can- sometimes smoking) are common among women, although
cer of the lip and oral cavity and “other pharynx” in the top this varies considerably from region to region.
20 countries in the world. Early this century, within Europe, the incidence of oral
There is wide geographical variation in the incidence cavity and pharyngeal cancers (C00–14) among males var-
of oral cancer and of “other pharynx” cancers (C09–C10) ied substantially between 5.9 (Finland) and 32 (France)
(Table 1.1). Figure 1.4 shows incidence rates for cancers per 100,000 per annum (8). Incidence rates among females
of the lip and oral cavity, in quintiles, for the countries of were highest in northern and western Europe, but were
the world. It has been apparent for decades that the global consistently lower than those for males. The male-to-
picture for head and neck cancer is dominated by the inci- female ratio decreased during the last 10 years and recently
dence of oral cancer in southern Asia and of oral cavity varied between 1.5 and 2.5 in northern Europe to 7.7 in
plus nasopharyngeal cancer in East Asia. In the 1980s, in Lithuania. Between 1990 and 1999, the U.K. incidence
India, Bangladesh, Pakistan and Sri Lanka, oral cancer was rates for oral cancers rose in males of all ages from 6.5 to
(a) World: Male, all ages

40
35
30
25
ASR (W)
20
15
10
0
Pr ng
Oe L h
ph a
x
lo ate
a
St um
us
l c ia
rc a
an La m
h in
Ot a nx
ph r
Lip ka a
tip Th er
ey
ne Pa vity
llb nx
Ka lym stis
s s as
Na yel d
n Kid r
so ive
yn
so om
om
si om
e
ac
Le om
m oi
, o em
r p sk
te
dd
ag
dd
ou re
Lu
om ry
lym n
Ga ary
Co ost
ct
om
ar
e
le yr
a
ys
rv nc
po ph
he of
T
ph
la
a
re
Bl
sa
ra
u
n
ki
ki
el
ul
dg
dg
M
n,
Ho
Ho
ai
Br
n-
Incidence
No
Mortality
World: Female, all ages

(b) 50
45
40
35
30
ASR (W)
25
20
15
10
0
rv um
ki ph a
rp ng
om i
a
tip Bl er
ph a
uk a
Pa mia
in
r t
an sy y
Co Lu i
sa x
Th y
h
Ho N ye er
O mp nx
po a x
ha s
la y
Li a o m
rv Kid s
St ter
p r
d
er
dg aso lom
lo as
om
er om
Le hom
o p ea
si ryn
e
ar
gu
yn
m e
llb v i t
ac
oi
dd
or f sk
le dd
om ste
M ou n
ly Liv
ly ary
ut
Co Bre
Ce ect
es cr
yr
ae
ar
Ga l c a
O
rc
th h
a
us
ix
O n
L
m
a
el s
p,
n
n
ki
Ka
ne
ul
dg
M
n,
Ho
ai
n-
Br
Incidence
No
Mortality
Figure 1.2 Global incidence rates for malignant neoplasms, age-standardized to the world population (ASR(W)), in
both sexes. (Globocan 2012. http://gco.iarc.fr/today/.)
8.3 per 100,000 (an increase of 18%) and in females from 3.8 for males and 1.4 for females (10), down from 6.9 to 2.3,
2.6 to 3.6 per 100,000 (an increase of 30%) and continues respectively, in 1975. This substantial improvement is not
to be a concern (9). reflected in most of the rest of the world.
In the USA, the death rate due to cancer of the oral cav- Apart from the traditional risk factors, it has been sug-
ity and pharynx per 100,000 population in 2007–2011 was gested that estrogen deficiency may influence susceptibility
Incidence rates worldwide / Age distributions 7
Lip, oral cavity, other pharynx

ASR (W) per 100,000, all ages
Male Female
Papua New Guinea
Bangladesh
Hungary
Sri Lanka
Maldives
France, La Reunion
Slovakia
Pakistan
Myanmar
Portugal
Timor-Leste
France (metropolitan)
France, Guadeloupe
Romania
India
Germany
Kazakhstan
Belgium
Belarus
Slovenia
40 30 20 10 0 10 20 30 40
Incidence
Mortality
Figure 1.3 Incidence and mortality rates, both sexes, for malignant neoplasms of the lip, oral cavity and pharynx, exclud-
ing nasopharynx, in the 20 countries with the highest rates in the world. (Globocan 2012 http://gco.iarc.fr/today/.)
to oral cancer in women; significantly, a younger mean age has been reported from many parts of the world (20–23), a
at menopause and higher rates of hysterectomy may influ- trend that appears to be continuing. There was a significant
ence the higher rates of oral cancer seen among younger increase in the incidence of cancers in the tongue and ton-
females (11). Data presented in this chapter are, whenever sils among 20–40-year-olds in the USA between 1973 and
possible, separated by sex. 2001 (24).In Germany, Czechoslovakia and Hungary, there
was an almost 10-fold rise in mortality from oral cancer
AGE DISTRIBUTIONS in men aged 35–44 (25), within a single generation at the
end of the last century. Robinson and Macfarlane showed
Oral cancer is usually a disease that occurs in males after a dramatic increase in incidence rates for younger males
the fifth decade of life. The mean age at presentation is in the in Scotland from the 1980s to the 1990s (26). In the high-
fifth and early sixth decades in Asian populations compared prevalence areas of the world, in many cases patients are less
with the seventh and eighth decades in the North American than 40 years old, probably owing to heavy use of various
population (12–17). Statistics in the USA for 1975–2011 forms of tobacco from an early age, although some recent
show that the median age at diagnosis for cancer of the oral Indian data have not shown this (27).
cavity and pharynx was 62 years (18). It is also clear that a number of cases of squamous cell
Several studies suggest that 4%–6% of oral cancers now carcinoma occur in both young and old patients in the
occur at ages younger than 40 years (19). An alarming absence of traditional risk factors, in which the disease
increase in incidence of oral cancers among younger people may pursue a particularly aggressive course, more so in the
Table 1.1 Estimated age-standardized incidence rate per elderly. A study conducted in southern England concluded
100,000 per annum (pa) for oral plus “other pharynx” that a substantial proportion of cases of younger people
cancers in 2012 diagnosed with oral cancer occur in the absence of known
risk factors (28). This, together with the relatively short
Male Female
duration of exposure in users, suggests that factors other
Area ASR (W) ASR (W)
than tobacco and alcohol are implicated in the develop-
World 8.8 3.2 ment of oral cancer in a significant minority of cases. Diets
More developed 11.7 3.5 poor in fresh fruits and vegetables were identified as con-
Less developed 7.7 3.1 ferring significant risk. There is now substantial evidence
Eastern Africa 5.5 3.4 that human papillomavirus (HPV) infections are driving
Middle Africa 5.3 2.4 this rise in younger adults but, fortunately, HPV-related
Northern Africa 3.6 2.5 oropharyngeal cancers respond well to radiotherapy, per-
Southern Africa 10.2 3.8 mitting treatment de-escalation and improved quality of
Western Africa 2.2 1.5
life. It is also suggested that greater attention should be paid
to familial antecedents of malignant neoplasms in younger
Caribbean 8.4 2.7
patients with oral cancer (29).
Central America 3.7 2.0
Age distribution curves for the major oral and pharyn-
South America 8.2 3.0
geal cancer sites are given for deliberately selected countries
Northern America 11.4 4.1 in Figures 1.5 and 1.6.
Eastern Asia: China 2.2 1.0 As shown in Figure 1.5, all oral and pharyngeal cancers
Eastern Asia: Japan 7.4 2.3 show a similar distribution. Most cases occur in the fifth
Eastern Asia: other 3.7 1.2 to seventh decades of life, presumably because decades of
Southeastern Asia 6.2 3.2 exposure to tobacco, alcohol and poor nutrition take time
South central Asia 16.2 6.1 to synergize with other agents in triggering malignant
Western Asia 3.5 2.0 transformation—or in allowing this to survive the host
Central and Eastern Europe 14.3 2.5 response! There are nevertheless a significant minority of
Northern Europe 9.3 4.1 cases appearing in the third and fourth decades of life. These
Southern Europe 9.1 2.6 attract much interest as, although associations with early
Western Europe 15.4 4.8 commencement of smoking and with unsafe alcohol use
Australia/New Zealand 11.5 4.4
can be demonstrated, a substantial minority of cases arise
without exposure to traditional risk factors; here, dietary
Melanesia 26.3 16.4
inadequacies and HPV infection are likely to be important,
Micronesia/Polynesia 6.4 1.0
as may inherited predisposition.
Incidence ASR
Both sexes
Cancer of the lip and oral cavity

5.1+
3.8–5.1
2.5–3.8
1.9–2.5
<1.9
No data
Figure 1.4 Age standardized incidence rates for cancers of the lip plus oral cavity, across the globe, presented in quintiles.
(http://gco.iarc.fr/today/home; Accessed January 10, 2018.)
Incidence rates worldwide / Ethnic variations 9
Mouth and pharynx ICD C01–14 exc lip, saliv gland and nasophar, male
180
160
140
120 USA, SEER (9 registries): Black

USA, SEER (9 registries): White
Brazil, Sao Paulo
Finland
Rate per 100,000
100
France, Calvados
Poland, Rzeszow
Russia, St Petersburg
80 UK, England, Thames
Australia, New South Wales
China, Shanghai City
India, Chennai
60
Japan, Osaka Prefecture
40
20
0
0– 10– 20– 30– 40– 50– 60– 70– 80–
Age
CI5-X. International agency for research on cancer (IARC)-22.11.2014
Figure 1.5 Male age-specific incidence curves for the mouth and pharynx for selected countries.
In the high-incidence age bands, there is an approxi- ETHNIC VARIATIONS

mately 4–10-fold difference in incidence, with disturbingly
high rates in northwest France, Brazil and south India among Variations by ethnicity are largely due to social and cultural
the countries selected here. Note the much worse situation practices and the influence of dietary and genetic factors,
in American blacks compared with whites, explained by a though the latter are less well quantified. Variations in
mixture of risk factor and socioeconomic reasons. Finland outcome are also contributed to by differences in access to
does comparatively well, which is not surprising in view of healthcare. Where cultural practices represent risk factors,
that nation’s success in reducing the prevalence of smok- their continuation by emigrants from high-incidence
ing, though alcohol abuse remains a social problem. What regions to other parts of the world results in comparatively
is surprising are the low rates recorded for Shanghai, in spite high cancer incidence rates in immigrant communities. This
of high smoking prevalence in this large city. China is cur- can also affect the sub-sites of oral cancer most commonly
rently developing a more comprehensive, nationwide cancer affected, as shown in a study from California (30). The
registry system so more cogent data will soon be available. highest age-adjusted oral cancer rates in the USA are found
As shown in Figure 1.6, rates for females are lower and among non-Hispanic men (17.5/100,000) followed by non-
international differences are less marked. Women in south Hispanic women (6.6/100,000), with Asian and Hispanic
India stand out, and this is related to the use of betel quid populations showing lower incidence rates compared with
and tobacco, together with low socioeconomic status. white (Caucasian) ethnic groups. Tongue cancer was the
Mouth and pharynx ICD C01–14 exc lip, saliv gland and nasophar, female
70
60
50
USA, SEER (9 registries): Black

USA, SEER (9 registries): White
Brazil, Sao Paulo
40 Finland
Rate per 100,000
France, Calvados
Poland, Rzeszow
Russia, St Petersburg
UK, England, Thames
30
Australia, New South Wales
China, Shanghai City
India, Chennai
Japan, Osaka Prefecture
20
10
0
0– 10– 20– 30– 40– 50– 60– 70– 80–
Age
CI5-X. International agency for research on cancer (IARC)-22.11.2014
Figure 1.6 Female age-specific incidence curves for the mouth and pharynx for selected countries.
most common type of oral cancer among every ethnicity. [ASIR] = 4.60) than among males (ASIR = 3.80). Excluding
Asians were more likely to develop their malignancy in the those involving the lip, these cancers were highest among
buccal mucosa, a reflection of continuing areca and tobacco c oloreds (ASIR = 5.72) and lowest among blacks (ASIR =
chewing habits. Another study showed that American 3.16). Incidence rates increased significantly among col-
Indians and Alaskan Natives overall had significantly ored South Africans over the period from 1992 to 2001
lower incidence rates than non-Hispanic whites (31). (p < .05), particularly for the oropharynx (available at http://
Several studies from the USA have demonstrated that repository.up.ac.za/bitstream/handle/2263/32412/AyoYusuf_
black patients with oral cancer have poorer overall and Trends(2013).pdf?sequence=1).
disease-specific survival than whites, mainly because of The age-adjusted incidence rate for oral and pharyngeal
their comparatively poor access to healthcare (32,33). This cancers is higher for south Asians than for other residents in
is especially concerning because the incidence of oral plus England, particularly among females (35). Interestingly, this
pharyngeal cancer for black men in the USA is so high study showed that British south Asian males have signifi-
and is the sixth most common site for malignant disease cantly better survival rates than their non-south Asian peers
amongst this group (34). in the southeast of England, possibly a reflection of the more
In the Republic of South Africa, among Asian/Indian indolent progress of tobacco/areca nut-induced lesions (35).
South Africans, oral and oropharyngeal cancer incidence rates According to the SEER statistics, incidence rates of oral
were higher among females (Age-standardised i ncidence rate cavity and pharynx cancers among black men and women
Mortality rates and trends 11
Age-adjusted SEER incidence rates

by race and sex
Oral cavity and pharynx, all ages,
35 1975–2012 (SEER 9)
30
25
Rate per 100,000
20
15
10
0
5 0 5 0 5 0 5 0 2
197 198 198 199 199 200 200 201 201
Year of diagnosis
White male White female

Black male Black female
Figure 1.7 Incidence rates of cancer of the oral cavity and pharynx among black and white people in USA from 1975
to 2012.
declined dramatically throughout the period from 1975 to Figure 1.8 shows that trends in mortality over time are
2012 compared with white men and women. In 2012, inci- important to track and to understand. Hungary is a disas-
dence rates for black men and women were less than for ter, though a declining trend is evident from the year 2003.
white people (see Figure 1.7) (10). Russia remains a concern. France demonstrates what can be
achieved. The overall modest downward trend in the other
countries illustrated is encouraging.
Figure 1.9 shows that, although only approximately
MORTALITY RATES AND TRENDS a tenth of the male rate, Hungarian females remain a
challenge.
As with incidence rates and trends, there is much geo- Current male death rates for oral and pharyngeal cancer
graphical variation. Figure 1.3 plots age-standardized mor- around the world are seen vividly in Figure 1.8. There was a
tality rates for lip, oral cavity and other pharynx cancers steady rise in oral cancer mortality in men from the 1950s to
(ICD-10: C00–14 except C11) in the top 20 countries in the late 1980s in most western European countries (37), but this
world in the year 2012. Mortality was highest in Papua New trend has since declined in France, China and Hong Kong,
Guinea and countries in the southeast Asian region. Several which had exceedingly high rates in the past. Unfortunately,
European countries, namely France, Hungary and in the in most countries in central and Eastern Europe, oral can-
former Czechoslovakia, also have a high ranking. This is cer mortality in men continued to rise, reaching exceed-
historically linked to heavy alcohol and tobacco use in these ingly high rates in Hungary, Slovakia, Slovenia and the
communities (Table 1.2). Russian Federation at the end of the last century. Hungary,
Trends of age-standardized (world population) mortal- Ukraine, Estonia and Bulgaria showed more than a 100%
ity rates for the lip, oral cavity and other pharynx cancer increase in mortality rates for men during the 20-year
sites of interest within selected countries over the past three period up to the turn of the millennium. Even though the
to six decades are presented in Figures 1.8 and 1.9, derived rates of oral cancer are comparatively low among women
from the WHO mortality database (36). (Figure 1.9), there was an increase in several countries in
Table 1.2 Mortality data extracted from the GLOBOCAN 2012 database for comparison with the incidence data in Table 1.1
Other pharynx (ICD C09–10, C12–14)

Mouth (ICD C00–08)
Being tonsil, remainder of oropharynx,
Being lip, all of tongue, all of pyriform fossa, hypopharynx and sites not
mouth and major salivary glands otherwise specified amongst C00–C13
Country Male Female Male Female
World 2.7 1.2 2.2 0.5
More developed 2.3 0.6 2.2 0.3
Less developed 2.8 1.4 2.2 0.5
Africa 2.1 1.3 0.9 0.4
Eastern Africa 3.2 1.9 0.9 0.5
Middle Africa 2.9 1.4 1.6 0.6
Northern Africa 1.3 0.8 0.6 0.6
Southern Africa 2.8 1.0 2.2 0.6
Western Africa 1.2 1.0 0.5 0.1
Caribbean 2.0 0.6 2.4 0.6
Central America 0.8 0.5 0.7 0.2
South America 2.2 0.7 2.2 0.4
Northern America 1.2 0.5 1.2 0.3
Asia 3.0 1.4 2.4 0.5
Eastern Asia 1.1 0.5 0.7 0.1
Southeastern Asia 1.9 1.2 2.1 0.5
South central Asia 6.3 3.0 5.3 1.2
Western Asia 1.0 0.6 0.6 0.3
Europe 3.0 0.7 2.7 0.4
Central and Eastern Europe 5.1 0.7 3.8 0.3
Northern Europe 1.7 0.7 1.4 0.3
Southern Europe 1.9 0.6 1.8 0.3
Western Europe 2.0 0.6 2.7 0.5
Australia 1.3 0.6 1.2 0.3
New Zealand 1.4 0.7 1.0 0.2
Melanesia 14.4 10.2 2.8 0.4
Micronesia 2.0 0.0 0.0 0.0
Polynesia 1.4 0.0 2.0 0.3
Europe (notably Hungary, Belgium, Denmark and Slovakia) Atlanta. These striking differences are likely to be explained
over this period. These disturbing rises are thought to have by a number of factors including socioeconomic condition,
been related to high drinking and smoking patterns in these age, stage at diagnosis, continued presence or absence of
societies, together with poor diet in lower socioeconomic environmental risk factors and access to hospital services.
status groups. Fortunately, improvements are now evident. African–American patients have consistently poorer
The SEER program in the USA has reported an over- survival outcomes (See Figures 1.7 and 1.10) (39).
all fall in the mortality from oral and pharyngeal cancer A study in Mumbai, India, indicated a decreasing trend
between 2002 and 2011 of 1.87% per annum Table 1.3. in oral cancer incidence among Indian men, which was
Table 1.3 shows a fall in all mortality rates for oral and suggested may be due to a decrease in the use of betel quid/pan
pharyngeal cancer in the USA between 2002 and 2011. There and associated oral smokeless tobaccos over this period (40).
is a considerable fall in mortality among both black men and However, there continues to be a high prevalence of smokeless
black women (Annual percentage change [APC] of −3.7 and tobacco use among young adult men and women, especially
−2.7, respectively). Furthermore, the SEER data show higher in the form of Pan Parag/Gutka-type products, and cigarette
5-year relative survival rates for whites (64.3%) and blacks smoking is increasing. Overall, cancer of the upper aero-
(43.7%) who were diagnosed during the period 2004–2011 digestive tract (UADT) will increase, as indicated earlier (12).
than rates for those who were diagnosed during the period Population-based survival rates around the world show
1974–1976 (when rates for whites and blacks were 55% and little evidence of improvement over recent decades, despite
36.3%, respectively) (38). The 5-year survival rates in the vast improvements in treatment modalities. Cure rates and
SEER registries range from a high of 72.1% for white women survival rates have improved with advances in surgical and
in Utah to a low of 24.8% for black men in metropolitan other techniques in highly specialized, high-volume treatment
Mortality rates and trends 13
Mortality from cancer of the lip, oral cavity and pharynx

age-standardised rate (world): male, all ages
25
Rate per 100,000 20
15
10
0
1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010
Year
Australia China: selected rural areas China: selected urban areas
Finland France Hungary
Russian Federation South Africa UK, England and Wales
United States of America
International agency for reasearch on cancer (IARC)-25.11.2014
Figure 1.8 Mortality from cancer of the lip, oral cavity and pharynx: male.
Mortality from cancer of the lip, oral cavity and pharynx

age-standardised rate (world): female, all ages
3
Rate per 100,000
0
1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010
Year
Australia China: selected rural areas China: selected urban areas
Finland France Hungary
Russian Federation South Africa UK, England and Wales
United States of America
International agency for reasearch on cancer (IARC)-25.11.2014
Figure 1.9 Mortality from cancer of the lip, oral cavity and pharynx: female.
Table 1.3 Mortality trends APC for oral and pharyngeal cancer in the USA between 2002 and 2011 by race and sex
All races White Black

Total Male Female Total Male Female Total Male Female
All ages −1.0a −0.9a −1.5a −0.6a −0.4a −1.3a −3.4a −3.7a −2.7a
Source: Howlader N et al. (eds). SEER Cancer Statistics Review, 1975–2011. Bethesda, MD: National Cancer Institute. Available from: http://
seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER website, April 2014 (10).
a APC in rate is statistically significantly different from zero (p < .05).
institutions. Regrettably, such highly expert management smokers, actinic keratosis, discoid lupus erythematosus,
is not yet uniformly available and it may be decades before dyskeratosis congenita and epidermolysis bullosa are
these results are reflected in population trends. described under the broad definition of OPMD (41,42).
LOBAL SCENARIO OF ORAL

G GLOBAL PREVALENCE OF OPMD
POTENTIALLY MALIGNANT DISORDERS
(OPMD) AND LARYNGEAL LEUKOPLAKIA Estimates of the global prevalence of OPMD range from 1% to
5% (43) although much higher prevalence rates are reported
The term “oral potentially malignant disorders” was from southeast Asia, usually with a male preponderance
recommended by an international working group convened (e.g. in Sri Lanka [11.3%] (44), Taiwan [12.7%] (45) and
by the WHO Collaborating Centre for Oral Cancer and Pacific countries like Papua New Guinea [11.7%] (46)). Wide
Precancer in London in 2005 (41). It conveys that not all geographical variations across countries and regions are
disorders described under this umbrella will transform mainly due to differences in sociodemographic characteristics,
into invasive cancer—at least not within the lifespan of the type and pattern of tobacco use and clinical definitions
the affected individual. Leukoplakia, erythroplakia, oral of disease (see Table 1.4). In Western countries, the overall
submucous fibrosis, lichen planus, palatal lesions in reverse prevalence is low and a decreasing trend over time is observed.
Age-adjusted U.S. mortality rates

by race and sex
15 Oral cavity and pharynx, all ages,
1975–2012
13
10
Rate per 100,000
0
5 0 5 0 5 0 5 0 2
197 198 198 199 199 200 200 201 201
Year of death
White male White female

Black male Black female
Figure 1.10 Cancer sites include invasive cases only unless otherwise noted. (Mortality source: US Mortality Files, National
Center for Health Statistics, CDC. Rates are per 100,000 and are age–adjusted to the 2000 US Std Population (19 age
groups—Census P25– 1130). Regression lines are calculated using the Joinpoint Regression Program Version 4.2.0,
April 2015, National Cancer Institute.)
Table 1.4 Summary of the prevalence of OPMD reported in the literature
Female/Male Age group

Ref. Country (year) Sampling method ratio (years) Disease entity Definition used Prevalence (%)
44 Sri Lanka (2008) Multi-stage 0.6/1.0 ≥30 OPMD WHO 1994 11.3
stratified cluster weighted for gender and
(MSSC) geographical location
47 Taiwan (2005) Random 0.9/1.0 ≥15 OPMD Not given 12.7
Leukoplakia 7.4
Erythroplakia 1.9
Lichen planus 2.9
OSF 1.6
48 USA (2003) MSSC 0.9/1.0 ≥20 Leukoplakia Kramer 1978 0.66 males and
Kramer 1980 0.21 females
49 Sri Lanka (2003) MSSC – 35–44 and OPMD Leukoplakia/ WHO 1994 4.1
65–74 erythoplakia 2.6
OSF 0.4
50 Spain (2002) Stratified, random 0.8/1.0 ≥30 Leukoplakia WHO 1978 1.6
Axell et al. 1984
51 Germany (2000) Stratified, random 1.0/1.0 35–44 Leukoplakia Axell 1976 1.6
0.7/1.0 65–74 Leukoplakia Zain 1995 1.0
WHO-ICD-DA
52 Japan (2000) All invited 0.4/1.0 Male >40, Leukoplakia WHO 1980 0.19
female >20 Lichen planus 0.21
53 Malaysia (1997) Stratified, random 0.7/1.0 ≥25 Leukoplakia WHO 1978 0.96
Erythroplakia Axell et al. 1984 0.01
OSF 0.06
Lichen planus 0.38
54 The Netherlands Waiting room 0.9/1.0 13–93 Leukoplakia Axell 1984 0.6
(1996) Axell 1996
Schepman 1995
55 Hungary (1991) Random 0.7/1.0 All age Leukoplakia Axell 1984 1.3
groups Lichen planus 0.1
56 Japan (1991) Factory workers 0.5/1.0 18–63 Leukoplakia Axell 1984 2.5
57 Sweden (1987) Stratified random Not found ≥15 Lichen planus Axell 1976 1.9
58 Sweden (1987) All-invited residents 0.9/1.0 ≥15 Leukoplakia Axell 1976 3.6
OSF = oral submucous fibrosis; WHO-ICD-DA = World Health Organisation-International Classification of Diseases-Dental Addendum.
Mortality rates and trends / Global prevalence of OPMD 15
Petti (59) conducted a meta-analysis of 23 primary stud- studies give rates of transformation from 0% to 3.5% over
ies on oral leukoplakia from international data published varying time periods. A recent comprehensive systematic
between 1986 and 2002. The point-prevalence estimates review evaluated 7806 patients with OLP, amongst which
were 1.49% (95% confidence interval [CI] 1.42%–1.56%) and a mere 85 (1.09%) developed SCC in an average follow-up
2.6% (random effect, 95% CI 1.72%–2.74%). Leukoplakia time of 51.4 months. Average age at onset of squamous
was significantly more prevalent among males (prevalence cell carcinoma (SCC) was 60.8 years, with a slight female
ratio 3.22), but no difference was found between geographi- preponderance. The most common subsite of malignant
cal areas and between younger and older adults. Using these transformation was the tongue (68). Size is also a critical
data, Petti calculated that the crude annual oral cancer inci- determinant (69).
dence rate attributable to leukoplakia would be between 6.2
and 29.1 per 100,000, thus suggesting that the global num- REFERENCES
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Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F.
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MALIGNANT TRANSFORMATION 4. World Health Organization. Control of oral cancer in
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Risk of malignant transformation varies from site to site 5. National Cancer Control Programme Sri Lanka.
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study to study (61–63). A classic study conducted in the Colombo: NCCP, 2015.
1970s with follow-up over 7 years of over 30,000 Indian vil- 6. Ministry of Health Malaysia. Second report of the
lagers showed transformation rates from 10–24 per 100,000 National Cancer Registry, Cancer Incidence in
per year (62). Another classic study from the early 1980s, a Malaysia 2003. Available from: ghdx.healthdata
hospital-based study in Californian patients with oral leu- .org/organizations/national-cancer-registry-ministry-
koplakia with a mean follow-up period of 7.2 years, revealed health-malaysia; Accessed January 10, 2018.
a malignant transformation rate of 17.5% (63). Rates for hos- 7. Brandizzi D, Chuchurru JA, Lanfranchi HE, Cabrini RL.
pital-based studies are, unsurprisingly, consistently higher Analysis of the epidemiological features of oral cancer
than community-based studies because of sampling bias. in the city of Buenos Aires. Acta Odontol Latinoam
Petti (59) has estimated a mean global prevalence of 2.6% 2005;18(1):31–5.
for leukoplakia and a mean global transformation rate of 8. Karim-Kos HE, de Vries E, Soerjomataram I, Lemmens
1.36% per year (95% CI 0.69–2.03). Extrapolating from these V, Siesling S, Coebergh JW. Recent trends of cancer
figures suggests that considerably more oral squamous cell in Europe: a combined approach of incidence, survi
carcinoma (OSCC) should have been reported in recent times, val and mortality for 17 cancer sites since the 1990s.
a possible reason being under-reporting of cases of oral cancer Eur J Cancer 2008;44(10):1345–89.
in the developing world. More recently, a careful study of 1,357 9. Conway DI, Stockton DL, Warnakulasuriya KA,
patients with an OPMD from the south of England revealed Ogden G, Macpherson LM. Incidence of oral and
that 2.6% of cases transformed into invasive cancer for a total oropharyngeal cancer in United Kingdom (1990–
person follow-up time of 12,273 years (mean 9.04 years). The 1999)—recent trends and regional variation. Oral
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malignant transformation (64), especially if aneuploid (65). 10. Howlader N, Noone AM, Krapcho M et al. (eds).
Similar findings come from a study of leukoplakia in Shanghai SEER Cancer Statistics Review, 1975–2011. Bethesda,
(66). A study from a dysplasia clinic in the north of England MD: National Cancer Institute. Available from: http://
confirms the lateral tongue as a high-risk site and that non- seer.cancer.gov/csr/1975_2011/, based on November
smokers were 7.1-times more likely to undergo malignant 2013 SEER data submission, posted to the SEER
transformation compared to heavy smokers (67). website, April 2014.
Controversy continues as to whether or not oral lichen 11. Suba Z. Gender-related hormonal risk factors for oral
planus (OLP) should be considered an OPMD. Published cancer. Pathol Oncol Res 2007;13(3):195–202.
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the most deeply are often the least capable of expressing their
feelings, and a speechless tongue is with them the result of a full
heart. Besides, you are sure to be repaid for a good action at some
time or another. Like seed sown in the Nile, “the bread cast upon the
waters,” it may not come back to you for many days, but come back
at last it most certainly will. Would you like your change in silver or in
gold? Will you have it in a few graceful, well-chosen expressions, or
in the sterling coin of silent love with its daily thoughts and nightly
prayers; or, better still even than these, will you waive your claim to it
down here, and have it carried to your account above? I am
supposing yours is not one of those natures which have arrived at
the highest, the noblest type of benevolence, and give their gold
neither for silver nor for copper, but freely without return at all. To
these I can offer no encouragement, no advice. Their grapes are
ripened, their harvest is yellow, the light is already shining on them
from the golden hills of heaven.
CHAPTER VI
A DAY THAT IS DEAD
I have been burning old letters to-night; their ashes are fluttering in
the chimney even now; and, alas! while they consume, fleeting and
perishable like the moments they record, “each dying ember” seems
to have “wrought its ghost” upon my heart. Oh! that we could either
completely remember or completely forget. Oh! that the image of
Mnemosyne would remain close enough for us to detect the flaws in
her imperishable marble, or that she would remove herself so far as
to be altogether out of sight. It is the golden haze of “middle
distance” that sheds on her this warm and tender light. She is all the
more attractive that we see her through a double veil of retrospection
and regret, none the less lovely because her beauty is dimmed and
softened in a mist of tears.
Letter after letter they have flared, and blackened, and shrivelled
up. There is an end of them—they are gone. Not a line of those
different handwritings shall I ever see again. The bold, familiar
scrawl of the tried friend and more than brother; why does he come
back to me so vividly to-night? The stout heart, the strong arm, the
brave, kind face, the frank and manly voice. We shall never tread the
stubble nor the heather side by side again; never more pull her up
against the stream, nor float idly down in the hot summer noons to
catch the light air off the water on our heated faces; to discourse, like
David and Jonathan, of all and everything nearest our hearts. Old
friend! old friend! wherever you are, if you have consciousness you
must surely sometimes think of me; I have not forgotten you. I
cannot believe you have forgotten me even there.
And the pains-taking, up-and-down-hill characters of the little child
—the little child for whom the angels came so soon, yet found it
ready to depart, whose fever-wasted lips formed none but words of
confidence and affection, whose blue eyes turned their last dim,
dying looks so fondly on the face it loved.
And there were letters harder to part with than these. Never mind,
they are burnt and done with; letters of which even the superscription
once made a kind heart leap with pleasure so intense it was almost
pain; letters crossed and re-crossed in delicate, orderly lines, bearing
the well-known cipher, breathing the well-known perfume, telling the
old, false tale in the old, false phrases, so trite and worn-out, yet
seeming always so fresh and new.
The hand that formed them has other tasks to occupy it now; the
heart from which they came is mute and cold. Hope withers, love
dies—times are altered. What would you have? It is a world of
change. Nevertheless this has been a disheartening job; it has put
me in low spirits; I must call “Bones” out of his cupboard to come and
sit with me.
“What is this charm,” I ask him, “that seems to belong so
exclusively to the past?—this ‘tender grace of a day that is dead’?
and must I look after it down the gulf into which it has dropped with
such irrepressible longing only because it will never come back to
me? Is a man the greater or wiser that he lived a hundred years ago
or a thousand? Are reputations, like wine, the mellower and the more
precious for mere age, even though they have been hid away in a
cellar all the time? Is a thing actually fairer and better because I have
almost forgotten how it looked when present, and shall never set
eyes on it again? I entertain the greatest aversion to Horace’s
laudator temporis acti, shall always set my face against the
superstition that ‘there were giants in those days’; and yet wherever I
went in the world previous to my retirement here that I might live with
you, I found the strange maxim predominate, that everything was
very much better before it had been improved!
“If I entered a club and expressed my intention of going to the
Opera, for instance, whatever small spark of enthusiasm I could
kindle was submitted to a wet blanket on the spot. ‘Good heavens!’
would exclaim some venerable philosopher of the Cynic and
Epicurean schools, ‘there is no opera now, nor ballet neither. My
good sir, the thing is done; it’s over. We haven’t an artist left. Ah! you
should have seen Taglioni dance; you should have heard Grisi sing;
you should have lived when Plancus was consul. In short, you
should be as old as I am, and as disgusted, and as gouty, and as
disagreeable!’
“Or I walked into the smoking-room of that same resort, full of
some athletic gathering at Holland Park, some ’Varsity hurdle-race,
some trial of strength or skill amongst those lively boys, the
subalterns of the Household Brigade; and ere I could articulate
‘brandy and soda’ I had Captain Barclay thrown body and bones in
my face. ‘Walk, sir! You talk of walking?’ (I didn’t, for there had been
barely time to get a word in edgeways, or my parable would have
exhausted itself concerning a running high leap.) ‘But there is
nothing like a real pedestrian left; they don’t breed ’em, sir, in these
days: can’t grow them, and don’t know how to train them if they
could! Show me a fellow who would make a match with Barclay to-
day. Barclay, sir, if he were alive, would walk all your best men down
after he came in from shooting. Ask your young friends which of ’em
would like to drive the mail from London to Edinburgh without a
greatcoat! I don’t know what’s come to the present generation. It
must be the smoking, or the light claret, perhaps. They’re done,
they’re used up, they’re washed out. Why, they go to covert by
railway, and have their grouse driven to them on a hill! What would
old Sir Tatton or Osbaldeston say to such doings as these? I was at
Newmarket, I tell you, when the Squire rode his famous match—two
hundred miles in less than nine hours! I saw him get off old Tranby,
and I give you my honour the man looked fresher than the horse!
Don’t tell me. He was rubbed down by a couple of prize-fighters
(there were real bruisers in those days, and the best man used to
win), dressed, and came to dinner just as you would after a five-mile
walk. Pocket Hercules, you call him—one in a thousand? There were
hundreds of such men in my day. Why, I recollect in Tom Smith’s
time that I myself——’
“But at this point I used to make my escape, because there are
two subjects on which nobody is so brilliant as not to be prolix, so
dull as not to be enthusiastic—his doings in the saddle and his
adventures with the fair. To honour either of these triumphs he blows
a trumpet-note loud and long in proportion to the antiquity of the
annals it records. Why must you never again become possessed of
such a hunter as Tally-Ho? Did that abnormal animal really carry you
as well as you think, neither failing when the ground was deep nor
wavering when the fences were strong? Is it strictly true that no day
was ever too long for him? that he was always in the same field with
the hounds? And have not the rails he rose at, the ditches he
covered so gallantly, increased annually in height and depth and
general impossibility ever since that fatal morning when he broke his
back, under the Coplow in a two-foot drain?
“You can’t find such horses now? Perhaps you do not give them
so liberal a chance of proving their courage, speed, and endurance.
“On the other topic it is natural enough, I dare say, for you to ‘yarn’
with all the more freedom that there is no one left to contradict.
People used enormous coloured silk handkerchiefs in that remote
period, when you threw yours with such Oriental complacency, and
the odalisques who picked it up are probably to-day so old and stiff
they could not bend their backs to save their lives. But were they
really as fond, and fair, and faithful as they seem to you now? Had
they no caprices to chill, no whims to worry, no rivals on hand, to
drive you mad? Like the sea, those eyes that look so deep and blue
at a distance, are green and turbid and full of specks when you come
quite close. Was it all sunshine with Mary, all roses with Margaret, all
summer with Jane? What figures the modern women make of
themselves, you say. How they offend your eye, those bare cheek-
bones, those clinging skirts, those hateful chignons! Ah! the cheeks
no longer hang out a danger-signal when you approach; the skirts
are no more lifted, ever such a little, to make room for you in the
corner of the sofa next the fire; and though you might have had locks
of hair enough once to have woven a parti-coloured chignon of your
own, it would be hopeless now to beg as much as would make a
finger-ring for Queen Mab. What is it, I say, that causes us to look
with such deluded eyes on the past? Is it sorrow or malice,
disappointment or regret? Are our teeth still on edge with the sour
grapes we have eaten or forborne? Do we glower through the
jaundiced eyes of malevolence, or is our sight failing with the shades
of a coming night?”
Bones seldom delivers himself of his opinion in a hurry. “I think,”
he says very deliberately, “that this, like many other absurdities of
human nature, originates in that desire for the unattainable which is,
after all, the mainspring of effort, improvement, and approach
towards perfection. Man longs for the impossible, and what is so
impossible as the past? That which hath vanished becomes
therefore valuable, that which is hidden attractive, that which is
distant desirable. There is a strange lay still existing by an old
Provençal troubadour, no small favourite with iron-handed, lion-
hearted King Richard, of which the refrain, ‘so far away,’ expresses
very touchingly the longing for the absent, perhaps only because
absent, that is so painful, so human, and so unwise. The whole story
is wild and absurd to a degree, yet not without a saddened interest,
owing to the mournful refrain quoted above. It is thus told in the
notes to Warton’s History of English Poetry:—
“‘Jeffrey Rudell, a famous troubadour of Provence, who is also
celebrated by Petrarch, had heard from the adventurers in the
Crusades the beauty of a Countess of Tripoli highly extolled. He
became enamoured from imagination, embarked for Tripoli, fell sick
on the voyage through the fever of expectation, and was brought on
shore at Tripoli, half-expiring. The countess, having received the
news of the arrival of this gallant stranger, hastened to the shore and
took him by the hand. He opened his eyes, and at once overpowered
by his disease and her kindness, had just time to say inarticulately
that having seen her he died satisfied. The countess made him a
most splendid funeral, and erected to his memory a tomb of porphyry
inscribed with an epitaph in Arabian verse. She commanded his
sonnets to be richly copied and illuminated with letters of gold, was
seized with a profound melancholy, and turned nun. I will endeavour
to translate one of the sonnets he made on his voyage, “Yret et
dolent m’en partray,” etc. It has some pathos and sentiment. “I
should depart pensive but for this love of mine so far away, for I
know not what difficulties I may have to encounter, my native land
being so far away. Thou who hast made all things and who formed
this love of mine so far away, give me strength of body, and then I
may hope to see this love of mine so far away. Surely my love must
be founded on true merit, as I love one so far away. If I am easy for a
moment, yet I feel a thousand pains for her who is so far away. No
other love ever touched my heart than this for her so far away. A
fairer than she never touched any heart, either so near or so far
away.’”
“It is utter nonsense, I grant you, and the doings of this love-sick
idiot seem to have been in character with his stanzas, yet is there a
mournful pathos about that wailing so far away which, well-worded,
well-set, and well-performed, would make the success of a drawing-
room song.
“If the Countess of Tripoli, who seems also to have owned a
susceptible temperament, had been his cousin and lived next door,
he would probably not have admired her the least, would certainly
never have wooed her in such wild and pathetic verse; but he gave
her credit for all the charms that constituted his own ideal of
perfection, and sickened even to death for the possession of his
distant treasure, simply and solely because it was so far away!
“What people all really love is a dream. The stronger the
imagination the more vivid the phantom that fills it; but on the other
hand, the waking is more sudden and more complete. If I were a
woman instead of a—a—specimen, I should beware how I set my
heart upon a man of imagination, a quality which the world is apt to
call genius, with as much good sense as there would be in
confounding the sparks from a blacksmith’s anvil with the blacksmith
himself. Such a man takes the first doll that flatters him, dresses her
out in the fabrications of his own fancy, falls down and worships, gets
bored, and gets up, pulls the tinsel off as quick as he put it on; being
his own he thinks he may do what he likes with it, and finds any
other doll looks just as well in the same light and decked with the
same trappings. Narcissus is not the only person who has fallen in
love with the reflection, or what he believed to be the reflection, of
himself. Some get off with a ducking, some are drowned in sad
earnest for their pains.
“Nevertheless, as the French philosopher says, ‘There is nothing
so real as illusion.’ The day that is dead has for men a more actual, a
more tangible, a more vivid identity than the day that exists, nay,
than the day as yet unborn. One of the most characteristic and
inconvenient delusions of humanity is its incapacity for enjoyment of
the present. Life is a journey in which people are either looking
forward or looking back. Nobody has the wisdom to sit down for half-
an-hour in the shade listening to the birds overhead, examining the
flowers underfoot. It is always ‘How pleasant it was yesterday! What
fun we shall have to-morrow!’ Never ‘How happy we are to-day!’ And
yet what is the past, when we think of it, but a dream vanished into
darkness—the future but an uncertain glimmer that may never
brighten into dawn?
“It is strange how much stronger in old age than in youth is the
tendency to live in the hereafter. Not the real hereafter of another
world, but the delusive hereafter of this. Tell a lad of eighteen that he
must wait a year or two for anything he desires very eagerly, and he
becomes utterly despondent of attaining his wish; but an old man of
seventy is perfectly ready to make arrangements or submit to
sacrifices for his personal benefit to be rewarded in ten years’ time or
so, when he persuades himself he will still be quite capable of
enjoying life. The people who purchase annuities, who plant trees,
who breed horses for their own riding are all past middle age.
Perhaps they have seen so many things brought about by waiting,
more particularly when the deferred hope had caused the sick
heart’s desire to pass away, that they have resolved for them also
must be ‘a good time coming,’ if only they will have patience and
‘wait a little longer.’ Perhaps they look forward because they cannot
bear to look back. Perhaps in such vague anticipations they try to
delude their own consciousness, and fancy that by ignoring and
refusing to see it they can escape the inevitable change. After all,
this is the healthiest and most invigorating practice of the two.
Something of courage seems wanting in man or beast when either is
continually looking back. To the philosopher ‘a day that is dead’ has
no value but for the lesson it affords; to the rest of mankind it is
inestimably precious for the unaccountable reason that it can never
come again.”
“Be it so,” I answered; “let me vote in the majority. I think with the
fools, I honestly confess, but I have also a theory of my own on this
subject, which I am quite prepared to hear ridiculed and despised.
My supposition is that ideas, feelings, delusions, name them how
you will, recur in cycles, although events and tangible bodies, such
as we term realities, must pass away. I cannot remember in my life
any experience that could properly be called a new sensation. When
in a position of which I had certainly no former knowledge I have
always felt a vague, dreamy consciousness that something of the
same kind must have happened to me before. Can it be that my soul
has existed previously, long ere it came to tenant this body that it is
so soon about to quit? Can it be that its immortality stretches both
ways, as into the future so into the past? May I not hope that in the
infinity so fitly represented by a circle, the past may become the
future as the future most certainly must become the past, and the
day that is dead, to which I now look back so mournfully, may rise
again newer, fresher, brighter than ever in the land of the morning
beyond that narrow paltry gutter which we call the grave?” I waited
anxiously for his answer. There are some things we would give
anything to know, things on which certainty would so completely alter
all our ideas, our arrangements, our hopes, and our regrets. Ignorant
of the coast to which we are bound, its distance, its climate, and its
necessities, how can we tell what to pack up and what to leave
behind? To be sure, regarding things material, we are spared all
trouble of selection; but there is yet room for much anxiety
concerning the outfit of the soul. For the space of a minute he
seemed to ponder, and when he did speak, all he said was this—
“I know, but I must not tell,” preserving thereafter an inflexible
silence till it was time to go to bed.
CHAPTER VII
THE FOUR-LEAVED SHAMROCK
We are all looking for it; shall we ever find it? Can it be cultivated in
hothouses by Scotch head-gardeners with high wages and Doric
accent? or shall we come upon it accidentally, peeping through
green bulrushes, lurking in tangled woodlands, or perched high on
the mountain’s crest, far above the region of grouse and heather,
where the ptarmigan folds her wings amongst the silt and shingle in
the clefts of the bare grey rock? We climb for it, we dive for it, we
creep for it on our belly, like the serpent, eating dust to any amount
in the process; but do we ever succeed in plucking such a specimen
as, according to our natures, we can joyfully place in our hats for
ostentation or hide under our waistcoats for true love?
Do you remember Sir Walter Scott’s humorous poem called the
“Search after Happiness”? Do you remember how that Eastern
monarch who strove to appropriate the shirt of a contented man
visited every nation in turn till he came to Ireland, the native soil
indeed of all the shamrock tribe; how his myrmidons incontinently
assaulted one of the “bhoys” whose mirthful demeanour raised their
highest hopes, and how
“Shelelagh, their plans was well-nigh after baulking,

Much less provocation will set it a-walking;
But the odds that foiled Hercules foiled Paddywhack.
They floored him, they seized him, they stripped him, alack!
Up, bubboo! He hadn’t a shirt to his back!”
Mankind has been hunting the four-leaved shamrock from the very
earliest times on record. I believe half the legends of mythology, half
the exploits of history, half the discoveries of science, originate in the
universal search. Jason was looking for it with his Argonauts when
he stumbled on the Golden Fleece; Columbus sailed after it in the
track of the setting sun, scanning that bare horizon of an endless
ocean, day after day, with sinking heart yet never-failing courage, till
the land-weeds drifting round his prow, the land-birds perching on his
spars, brought him their joyous welcome from the undiscovered
shore; Alexander traversed Asia in his desire for it; Cæsar dashed
through the Rubicon in its pursuit; Napoleon well-nigh grasped it
after Austerlitz, but the frosts and fires of Moscow shrivelled it into
nothing ere his hand could close upon the prize. To find it, sages
have ransacked their libraries, adepts exhausted their alembics,
misers hoarded up their gold. It is not twined with the poet’s bay-
leaves, nor is it concealed in the madman’s hellebore. People have
been for it to the Great Desert, the Blue Mountains, the Chinese
capital, the interior of Africa, and returned empty-handed as they
went. It abhors courts, camps, and cities; it strikes no root in palace
nor in castle; and if more likely to turn up in a cottage-garden, who
has yet discovered the humble plot of ground on which it grows?
Nevertheless, undeterred by warning, example, and the
experience of repeated failures, human nature relaxes nothing of its
persevering quest. I have seen a dog persist in chasing swallows as
they skimmed along the lawn; but then the dog had once caught a
wounded bird, and was therefore acting on an assured and tried
experience of its own. If you or I had ever found one four-leaved
shamrock, we should be justified in cherishing a vague hope that we
might some day light upon another.
The Knights of the Round Table beheld with their own eyes that
vision of the Holy Vessel, descending in their midst, which scattered
those steel-clad heroes in all directions on the adventure of the
Sangreal; but perhaps the very vows of chivalry they had registered,
the very exploits they performed, originated with that restless longing
they could not but acknowledge in common with all mankind for
possession of the four-leaved shamrock.
“And better he loved, that monarch bold,

On venturous quest to ride
In mail and plate, by wood and wold,
Than with ermine trapped and cloth of gold
In princely bower to bide.
The bursting crash of a foeman’s spear
As it shivered against his mail,
Was merrier music to his ear
Than courtier’s whispered tale.
And the clash of Caliburn more dear,
When on hostile casque it rung,
Than all the lays to their monarch’s praise
The harpers of Reged sung.
He loved better to bide by wood and river,
Than in bower of his dame Queen Guenevere;
For he left that lady, so lovely of cheer,
To follow adventures of danger and fear,
And little the frank-hearted monarch did wot
That she smiled in his absence on brave Launcelot.”
Oh! those lilting stanzas of Sir Walter’s, how merrily they ring on
one’s ear, like the clash of steel, the jingling of bridles, or the
measured cadence of a good steed’s stride! We can fancy ourselves
spurring through the mêlée after the “selfless stainless” king, or
galloping with him down the grassy glades of Lyonesse on one of his
adventurous quests for danger, honour, renown—and—the four-
leaved shamrock.
Obviously it did not grow in the tilt-yards at Caerleon or the palace
gardens of Camelot; nay, he had failed to find it in the posy lovely
Guenevere wore on her bosom. Alas! that even Launcelot, the flower
of chivalry, the brave, the courteous, the gentle, the sorrowing and
the sinful, must have sought for it there in vain.
Everybody begins life with a four-leaved shamrock in view, an
ideal of his own, that he follows up with considerable wrong-
headedness to the end. Such fiction has a great deal to answer for in
the way of disappointment, dissatisfaction, and disgust. Many
natures find themselves completely soured and deteriorated before
middle age, and why? Because, forsooth, they have been through
the garden with no better luck than their neighbours. I started in
business, we will say, with good connections, sufficient capital, and
an ardent desire to make a fortune. Must I be a saddened, morose,
world-wearied man because, missing that unaccountable rise in
muletwist, and taking the subsequent fall in grey shirtings too late, I
have only realised a competency, while Bullion, who didn’t want it,
made at least twenty thou.? Or I wooed Fortune as a soldier, fond of
the profession, careless of climate, prodigal of my person, ramming
my head wherever there was a chance of having it knocked off,
“sticking to it like a leech, sir; never missing a day’s duty, by Jove!
while other fellows were getting on the staff, shooting up the country,
or going home on sick leave.” So I remain nothing but an overworked
field-officer, grim and grey, with an enlarged liver, and more red in my
nose than my cheeks, while Dawdle is a major-general commanding
in a healthy district, followed about by two aides-de-camp, enjoying a
lucrative appointment with a fair chance of military distinction. Shall I
therefore devote to the lowest pit of Acheron the Horse Guards, the
War Office, H.R.H. the Commander-in-Chief, and the service of Her
Majesty the Queen? How many briefless barristers must you multiply
to obtain a Lord Chancellor, or even a Chief Baron? How many
curates go to a bishop? How many village practitioners to a
fashionable doctor in a London-built brougham? Success in every
line, while it waits, to a certain extent, on perseverance and capacity,
partakes thus much in the nature of a lottery, that for one prize there
must be an incalculable number of blanks.
I will not go so far as to say that you should abstain from the liberal
professions of arts or arms, that you should refrain from taking your
ticket in the lottery, or in any way rest idly in mid-stream, glad to
“Loose the sail, shift the oar, let her float down,
Fleeting and gliding by tower and town;”
but I ask you to remember that the marshal’s baton can only be in
one conscript’s knapsack out of half a million; that wigs and mitres,
and fees every five minutes, fall only to one in ten thousand; that
although everybody has an equal chance in the lottery, that chance
may be described as but half a degree better than the cipher which
represents zero.
There is an aphorism in everybody’s mouth about the man who
goes to look for a straight stick in the wood. Hollies, elms, oaks,
ashes, and alders he inspects, sapling after sapling, in vain. This one
has a twist at the handle, that bends a little towards the point; some
are too thick for pliancy, some too thin for strength. Several would do
very well but for the abundant variety that affords a chance of finding
something better. Presently he emerges at the farther fence, having
traversed the covert from end to end, but his hands are still empty,
and he shakes his head, thinking he may have been over-fastidious
in his choice. A straight stick is no easier to find than would be a
four-leaved shamrock.
The man who goes to buy a town house or rent a place in the
country experiences the same difficulty. Up-stairs and down-stairs he
travels, inspecting kitchen-ranges, sinks and sculleries, attics,
bedrooms, boudoirs, and housemaids’ closets, till his legs ache, his
brain swims, and his temper entirely gives way. In London, if the
situation is perfect, there is sure to be no servants’ hall, or the
accommodation below-stairs leaves nothing to be desired, but he
cannot undertake to reside so far from his club. These difficulties
overcome, he discovers the butler’s pantry is so dark no servant of
that fastidious order will consent to stay with him a week. In the
country, if the place is pretty the neighbourhood may be
objectionable: the rent is perhaps delightfully moderate, but he must
keep up the grounds and pay the wages of four gardeners. Suitable
in every other respect, he cannot get the shooting; or if no such
drawbacks are to be alleged, there is surely a railway through the
park, and no station within five miles. Plenty of shamrocks grow, you
see, of the trefoil order, green, graceful, and perfectly symmetrical. It
is that fourth leaf he looks for, which creates all his difficulties.
The same with the gentleman in search of a horse, the same with
Cœlebs in search of a wife. If the former cannot be persuaded to put
up with some little drawback of action, beauty, or temper, he will
never know that most delightful of all partnerships, the sympathy
existing between a good horseman and his steed. If the latter
expects to find a perfection really exist, which he thinks he has
discovered while dazzled by the glamour surrounding a man in love,
he deserves to be disappointed, and he generally is. Rare, rare
indeed are the four-leaved shamrocks in either sex; thrice happy
those whom Fate permits to win and wear them even for a day!
What is it we expect to find? In this matter of marriage more than
in any other our anticipations are so exorbitant that we cannot be
surprised if our “come-down” is disheartening in proportion.
“Where is the maiden of mortal strain

That may match with the Baron of Triermain?
She must be lovely, constant, and kind,
Holy and pure, and humble of mind,” etc.
(How Sir Walter runs in my head to-night.) Yes, she must be all this,
and possess a thousand other good qualities, many more than are
enumerated by Iago, so as never to descend for a moment from the
pedestal on which her baron has set her up. Is this indulgent? is it
even reasonable? Can he expect any human creature to be always
dancing on the tight-rope? Why is Lady Triermain not to have her
whims, her temper, her fits of ill-humour, like her lord? She must not
indeed follow his example and relieve her mind by swearing “a good,
round, mouth-filling oath,” therefore she has the more excuse for
feeling at times a little captious, a little irritable, what she herself calls
a little cross. Did he expect she was an angel? Well, he often called
her one, nay, she looks like it even now in that pretty dress, says my
lord, and she smiles through her tears, putting her white arms round
his neck so fondly that he really believes he has found what he
wanted till they fall out again next time.
Men are very hard in the way of exaction on those they love. All
“take” seems their motto, and as little “give” as possible. If they
would but remember the golden rule and expect no more than
should be expected from themselves, it might be a better world for
everybody. I have sometimes wondered in my own mind whether
women do not rather enjoy being coerced and kept down. I have
seen them so false to a kind heart, and so fond of a cruel one. Are
they slaves by nature, do you conceive, or only hypocrites by
education? I suppose no wise man puzzles his head much on that
subject. They are all incomprehensible and all alike!
“How unjust!” exclaims Bones, interrupting me with more vivacity
than usual. “How unsupported an assertion, how sweeping an
accusation, how unfair, how unreasonable, and how like a man! Yes,
that is the way with every one of you; disappointed in a single
instance, you take refuge from your own want of judgment, your own
mismanagement, your own headlong stupidity, in the condemnation
of half the world! You open a dozen oysters, and turn away
disgusted because you have not found a pearl. You fall an easy prey
to the first woman who flatters you, and plume yourself on having
gained a victory without fighting a battle. The fortress so easily won
is probably but weakly garrisoned, and capitulates ere long to a fresh
assailant. When this has happened two or three times, you veil your
discomfiture under an affectation of philosophy and vow that women
are all alike, quoting perhaps a consolatory scrap from Catullus—
‘Quid levius plumâ? pulvis. Quid pulvere? ventus.

Quid vento? mulier. Quid muliëre? nihil?’
But Roman proverbs and Roman philosophy are unworthy and

delusive. There is a straight stick in the wood if you will be satisfied
with it when found; there is a four-leaved shamrock amongst the
herbage if you will only seek for it honestly on your knees. Should
there be but one in a hundred women, nay, one in a thousand, on
whom an honest heart is not thrown away, it is worth while to try and
find her. At worst, better be deceived over and over again than sink
into that deepest slough of depravity in which those struggle who,
because their own trust has been outraged, declare there is no faith
to be kept with others; because their own day has been darkened,
deny the existence of light.
“You speak feelingly,” I observe, conscious that such unusual
earnestness denotes a conviction he will get the worst of the debate.
“You have perhaps been more fortunate than the rest. Have you
found her, then, this hundredth woman, this prize, this pearl, this
black swan, glorious as the phœnix and rare as the dodo? Forgive
my argumentum ad hominem, if I may use the expression, and
forgive my urging that such good fortune only furnishes one of those
exceptions which, illogical people assert, prove the rule.” There is a
vibration of his teeth wanting only lips to become a sneer, while he
replies—
“In my own case I was not so lucky, but I kept my heart up and
went on with my search to the end.”
“Exactly,” I retort in triumph; “you, too, spent a lifetime looking for
the four-leaved shamrock, and never found it after all. But I think
women are far more unreasonable than ourselves in this desire for
the unattainable, this disappointment when illusion fades into reality.
Not only in their husbands do they expect perfection, and that, too, in
defiance of daily experience, of obvious incompetency, but in their
servants, their tradespeople, their carriages, their horses, their
rooms, their houses, the dinners they eat, and the dresses they
wear. With them an avowal of incapacity to reconcile impossibilities
stands for wilful obstinacy, or sheer stupidity at best. They believe
themselves the victims of peculiar ill-fortune if their coachman gets
drunk, or their horses go lame; if milliners are careless or ribbons
unbecoming; if chimneys smoke, parties fall through, or it rains when
they want to put on a new bonnet. They never seem to understand
that every ‘if’ has its ‘but,’ every pro its con. My old friend, Mr.
Bishop, of Bond Street, the Democritus of his day (and may he live
as long!), observed to me many years ago, when young people went
mad about the polka, that the new measure was a type of everything
else in life, ‘What you gain in dancing you lose in turning round.’ Is it
not so with all our efforts, all our undertakings, all our noblest
endeavours after triumph and success? In dynamics we must be
content to resign the maximum of one property that we may preserve
the indispensable minimum of another, must allow for friction in
velocity, must calculate the windage of a shot. In ethics we must
accept fanaticism with sincerity, exaggeration with enthusiasm, over-
caution with unusual foresight, and a giddy brain with a warm,
impulsive heart. What we take here we must give yonder; what we
gain in dancing we must lose in turning round!
“But no woman can be brought to see this obvious necessity. For
the feminine mind nothing is impracticable. Not a young lady eating
bread and butter in the school-room but cherishes her own vision of
the prince already riding through enchanted forests in her pursuit.
The prince may turn out to be a curate, a cornet, or a count, a duke
or a dairy-farmer, a baronet or a blacking-maker, that has nothing to
do with it. Relying on her limitless heritage of the possible, she feels
she has a prescriptive right to the title, the ten thousand a year, the
matrimonial prize, the four-leaved shamrock. Whatever else turns
up, she considers herself an ill-used woman for life, unless all the
qualities desirable in man are found united in the person and
fortunes of her husband; nay, he must even possess virtues that can
scarce possibly co-exist. He must be handsome and impenetrable,
generous and economical, gay and domestic, manly but never from
her side, wise yet deferring to her opinion in all things, quick-sighted,
though blind to any drawbacks or shortcomings in herself. Above all,
must he be superlatively content with his lot, and unable to discover
that by any means in his matrimonial venture, ‘what he gained in
dancing he has lost in turning round.’
“I declare to you I think if Ursidius[2] insists on marrying at all, that
he had better select a widow; at least he runs at even weights
against his predecessor, who, being a man, must needs have
suffered from human weakness and human infirmities. The chances
are that the dear departed went to sleep after dinner, hated an open
carriage, made night hideous with his snores under the connubial
counterpane, and all the rest of it. A successor can be no worse,
may possibly appear better; but if he weds a maiden, he has to
contend with the female ideal of what a man should be! and from
such a contest what can accrue but unmitigated discomfiture and
disgrace?
“Moreover, should he prove pre-eminent in those manly qualities
women most appreciate, he will find that even in those they prefer to
accept the shadow for the substance, consistently mistaking
assertion for argument, volubility for eloquence, obstinacy for
resolution, bluster for courage, fuss for energy, and haste for speed.
“On one of our greatest generals, remarkable for his gentle,
winning manner in the drawing-room as for his cool daring in the
field, before he had earned his well-merited honours, I myself heard
this verdict pronounced by a jury of maids and matrons: ‘Dear! he’s
such a quiet creature, I’m sure he wouldn’t be much use in a battle!’
No; give them Parolles going to recover his drum, and they have a
champion and a hero exactly to their minds, but they would scarcely
believe in Richard of the Lion-Heart if he held his peace and only set
his teeth hard when he laid lance in rest.
“Therefore it is they tug so unmercifully at the slender thread that
holds a captive, imagining it is by sheer strength the quiet creature
must be coerced. Some day the pull is harder than usual, the thread
breaks, and the wild bird soars away, free as the wind down which it
sails, heedless of lure and whistle, never to return to bondage any
more. Then who so aghast as the pretty, thoughtless fowler, longing
and remorseful, with the broken string in her hand?
“She fancied, no doubt, her prisoner was an abnormal creature,
rejoicing in ill-usage; that because it was docile and generous it must
therefore be poor in spirit, slavish in obedience, and possessing no
will of its own. She thought she had found a four-leaved shamrock,
and this is the result!
“But I may talk for ever and end where I began. Men you may
convince by force of argument, if your logic is very clear and your
examples or illustrations brought fairly under their noses; but with the
other sex, born to be admired and not instructed, you might as well
pour water into a sieve. Can you remember a single instance in
which with these, while a word of entreaty gained your point
forthwith, you might not have exhausted a folio of argument in vain?”
He thinks for a minute, and then answers deliberately, as if he had
made up his mind—
“I never knew but one woman who could understand reason, and
she wouldn’t listen to it!”
CHAPTER VIII
RUS IN URBE
Romæ Tibur Amem, ventosus. Tibure Romam! quoth the Latin

satirist, ridiculing his own foibles, like his neighbour’s, with the
laughing, half-indulgent banter that makes him the pleasantest, the
chattiest, and the most companionable of classic writers. How he
loved the cool retirement of his Sabine home, its grassy glades, its
hanging woodlands, its fragrant breezes wandering and whispering
through those summer slopes, rich in the countless allurements of a
landscape that—
“Like Albunea’s echoing fountain,

All my inmost heart hath ta’en;
Give me Anio’s headlong torrent,
And Tiburnus’ grove and hills,
And its orchards sparkling dewy,
With a thousand wimpling rills,”
as Theodore Martin translates his Horace, or thus, according to Lord

Ravensworth—
“Like fair Albunea’s sybil-haunted hall,

By rocky Anio’s echoing waterfall,
And Tibur’s orchards and high-hanging wood,
Reflected graceful in the whirling flood.”
His lordship, you observe, who can himself write Latin lyrics as
though he had drunk with Augustus, and capped verses with Ovid,
makes the second syllable of Albunea long, and a very diffuse
argument might be held on this disputed quantity. Compare these
with the original, and say which you like best—
“Quam domus Albuneæ resonantis,

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Oral and oropharyngeal cancer Second

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Going to Strasbourg : an oral history of sexual

Jatin P. Shah, MD, MS (Surg), PhD (Hon),

Newell W. Johnson, CMG, FMedSci, MDSc, PhD,

© 2019 by Taylor & Francis Group, LLC

No claim to original U.S. Government works

Printed on acid-free paper

International Standard Book Number-13: 978-1-4987-0008-5 (Hardback)

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Names: Shah, Jatin P., editor. | Johnson, Newell W., editor.

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Preface to the second edition vii

Part I PATHOLOGY AND BIOLOGY 1

Part II CLINICAL MANAGEMENT 233

6 Clinical evaluation and differential diagnosis 235

17 Reconstructive surgery: Maxilla 425

Part III OUTCOMES AND FOLLOW-UP 439

19 Oncologic outcomes 441

Nishant Agrawal, MD Rachel A. Giese, MD

Nezar al-Hebshi, BDS, PhD Ralph W. Gilbert, MD, FRCSC

Jay O. Boyle, MD Prakash C. Gupta, DSc

Pathology and biology

NEWELL W. JOHNSON AND HEMANTHA AMARASINGHE

Definitions of oral cancer 3 Global scenario of oral potentially malignant

and 2011, apart from lesions of the salivary glands, gingivae,

Dementia and Alzheimer disease Dementia and Alzheimer disease

Cerebrovascular diseases Chronic lower respiratory diseases

Malignant neoplasms, stated or presumed to primary of

(a) World: Male, all ages

World: Female, all ages

Lip, oral cavity, other pharynx

Cancer of the lip and oral cavity

120 USA, SEER (9 registries): Black

In the high-incidence age bands, there is an approxi- ETHNIC VARIATIONS

USA, SEER (9 registries): Black

Age-adjusted SEER incidence rates

White male White female

Other pharynx (ICD C09–10, C12–14)

Mortality from cancer of the lip, oral cavity and pharynx

Rate per 100,000 20

International agency for reasearch on cancer (IARC)-25.11.2014

Mortality from cancer of the lip, oral cavity and pharynx

International agency for reasearch on cancer (IARC)-25.11.2014

All races White Black

 LOBAL SCENARIO OF ORAL

Age-adjusted U.S. mortality rates

White male White female

Female/Male Age group

“Shelelagh, their plans was well-nigh after baulking,

“And better he loved, that monarch bold,

“Where is the maiden of mortal strain

LOBAL SCENARIO OF ORAL