International seminar on

oral leukoplakia and associated lesions

related to tobaceo habits
Lund University, Maimo, S'weden, June 27-30, 1983

This compilation wa,s edited by h^A R, H, KRAMER, J , J , PINDBORG, AND M , SHEAR

This seminar was formally O|^| "RAKA,SH C. GUPTA

ish Ministry of Education and Culttiral Afikirs, tn -JAsic Dental Research Unit
Lund University and ils Dental Faculty and the Tata Instittitc of Fundamental
Research
Swedish Tobacco Company Bombay, India

LOUIS S. HANSEN
Division of Oral Pathology
THE ORGANIZING GOMMITTEE School of Denti,stry
University of California
TONY AXELL
San Francisco, CA, USA
Deparlmenl of Oral Surgery and Oral Medicine, Dental
Faculty, Lund University, Maimo, Sweden IVOR R. H . KRAMER
Department of Pathology
JENS J, PINDBORG Institute of Dental Surgery
Eastman Oeiilal Hospital
Deparlmenl of Oral Pathology, Royal Dental College and
London, F.ngland
Deparlmenl of Oral Medicine and Oral Surgery, U?}iver.nty
Hospital, Copenhagen, Denmark AKR T,ARSSON
Department of Oral Pathology
LARS RUNDQUIST Dental Faculty
Lund University
Department of Orat Surgery and Oral Medicine, Dental
Maimo, Sweden
Faculty, Lund University, Maimo, Sweden
MF.RVVN SHEAR
PALLE HOLMSTRUP Department of Oral Palhology
Department of Oral Palholog)', Royal Dental College attd University ofthe Witwatersrand
Johannesburg, South .Africa
Department of Oral Medicine and Oral Surgery, University
Hospitat, Copenhagen, Denmark LESLIE H . SOBIN
Dciiartmcnt of Gastroinlestinal
Pathology
Armed Forces Institute of Pathology
INVITED PARTICIPANTS TO THE SEMINAR WKRE Washington, D.C., USA
JOLAN BAN6CZV
Department of Conservative JAN SfjERNswARD
Dentistry Cancer Unit
Semmelwei,s Medical t^Jiiivcrsity World Health Organization
Budapest, Hungaty Geneva, Switzerland

A R N E IJtIRKllARDT SAMAN WARNAKHLASURIYA

Institulc of I';vllioU>gy Department of Oral Medieine
Univensity of Bern University Dental School
Bern, Swil/.erland Pcnideniya, Sri Lanka
14(3 AXELL, HOLMSTRUP, KRAMER, PINDBORG & SHEAR
ISAAC VAN DER WAAL
Institute of Pathology
Free University
Amsterdam, The Netherlands
ZHANG KUI-HUA
Department of Oral Medieine
Faculty of Stomatology, Beijing
Medical College
Beijing, People's Republic of China
PREFACE
Oral cancer has been the subjeel of several mono-
graphs and meetings in recent decades. Extensive
epidemiological studies, especially in Southeast
Asia, have thrown light on the occurrence of both
oral cancer and its precursor stages.
The World Health Organization has shown an
interest in the problem of oral precancer by estab-
lishing an International Reference Centre for Oral
Precancer, This led to the publication of a set of
clinical and histological diagnostic criteria,*
However, oral precancer still presents many
unsolved problems. Is it desirable to divide leuko-
plakias into various types? What aetiological factors
are involved in the pathogenesis of oral premalig-
nant lesions? What are the histological predictors of
malignant change? Which future studies will pro-
vide us with a better understanding ofthe behaviour
of oral precancer?
These and other questions were discussed during
a seminar held at the Dental Faculty of the Lund
University; an appropriate location, as the study of
oral mucosai diseases has been one of the major
research achievements of this Faculty,
The seminar comprised eight sessions, the main
contents of which are summarized below.
SESSION I
The significance of clinical criteria. Discussion of shortcom-
ings of pre.seni nomenclature based upon epidemiological
studies.
T, AXELL opened with a paper "Demographical and
clinical characteristics of some oral white lesions ,
He suggested that a diagnostic label should be a
part of language that could be used uniformly and
* Definition of leukoplakia and related lesions; an aid to studies
on oral precancer. Oral Surg 1978; 46: ,•) 18-39.
that could indicate therapeutic and/or pteventive
measures. It was important to consider whether the
label ieukoplakia presently fulfilled these criteria. In
the WHO publication (1978) leukoplakia was
defmed as "a white patch or plaque that cannot be
characterized, clinically or pathologically, as any
other disease,"
Based upon information frotn an examination of
20 333 individuals in a general population aged 15
years and above, he showed how the prevalence of
leukoplakia might vary between 0,7% and 24,8%
depending upon the clinical criteria used. He also
demonstrated that the distribution according to in-
traoral location is dependent upon the criteria used.
Included originally under the overall heading of
leukoplakia were the clinical conditions also known
as cheek and Up biting, smoker's palate and other
lesions attributed to smoking, snuH" dipper's lesion,
and frictional keratosis.
In the "Application ofthe International Classifi-
cation of Diseases to Dentistry and Stomatology"'*
cheek and lip biting and smoker's palate (leukoker-
atosis nieotina palati or nicotinic stomatitis), have
been separated from the designation leukoplakia,
AXELL asked whether other clinical entities could
be excluded as well. He eoneluded that the clinical
label leukoplakia presently did not fulfil the eriteria
of a diagnostic label initially mentioned,
], PINDBORG presented the following "Suggestions
for a elinical-aetiological classification of oral white
lesions previously called leukoplakia," in which the
premalignant lesions were believed to be arranged
according to increasing tendency for malignant
transformation.
Glassblower's white palch
Frictional keratosis
Lesions related to dental
Benign lesions restoratiotis ("galvatiic
lesions")
Smoker's palate
Smoker's white patch
Smoker's leukoplakia
Snuff dip])er's leukoplakia
Leukoplakia due to chew-
Premalignant lesions
ing tobacco or betel nut
Candida! letikoplakia
Idiopathic leukoplakia
2nd ed. Geneva: World Health Organi7.ati< 1978.

The group agreed that a revision of the present
classification was desirable and that the content of
the two papers could serve as a basis for further
discussions.
SESSION II
Discussion on published suggestions for nomenclature of oral
white tesions. Historical review with special emphasis on a
comparison of the Anglo-Atnerican, Scandinavian and the
German-Hungarian concepts.
A. BuRKHARDT Opened this session with a review of
"Nomenclature of oral white lesions," With regard
to the present concept of leukoplakia, he criticized
the defitiition which proposed a diagnosis by exclu-
sion. He made the point that "leukoplakia" and
"erythroplakia" were not disease entities, and posed
the question as lo whether those leukoplakias and
erythroplakias with known causes should be sepa-
rated from idiopathie lesions. He further discussed
exogenous and endogenous causes of these lesions.
He also proposed that the WHO definition might
be improved by adding the words ",,. and has be-
come independent of the causes which probably
induced it," This would separate the autonomous
high risk lesions from mostly harmle,ss, reversible
cause-dependent mucosai changes.
With regard to the malignant potential of the
different clinical forms of leukoplakia he showed
that in his sample of 200 cases, 3% of homogeneous
leukoplakias underwent malignant changes,
whereas the corresponding figures were 11% for
speckled leukoplakias without erosion and 38% for
speckled leukoplakias with erosion.
Lesion C linical
Stage (field diagnosis) di agnosis
0 No lesion
1 Low risk preeancer L Homogeneous leukoplakia
High risk precancer 1. SiK'ckled (nodular) leukoplakia I'or iin est igalion
2. Erythroplakia
3. Oral submucous
(dancer probable Squamous cell or verrucous
carcinoma
Oral Icttkoplakta and associated lesions 147
J, BANOGZY gave a "Review on the development
ofthe nomenclature of oral white lesions wilh special
emphasis on oral leukoplakia and the Hungarian
classification," Her sample of 670 patients was fol-
lowed for over 30 years. Six percent had undergone
malignant change; 31";, had been cured; 29,7%
improved; and 25,8% remained unchanged and
7,5% spread.
In her elassifiealion, leukoplakia simplex and leu-
koplakia verrucosa corresponded to the homoge-
neous leukoplakia; and leukoplakia erosiva corres-
ponded to the speckled leukoplakia ofthe Pindborg
classification, Leukoplakia simplex, in her sample,
showed the lowest frequency of malignanl transfor-
mation and leukoplakia erosiva the highest,
S, WARNAKULASURIYA reporied on "A new ap-
proach for a "field classification" of oral precancer
based upon treatment needs," His classification,
suitable lor use in population studies utilizing pri-
mary health care workers, is shown below (table).
The general discussion revolved around three
points: 1) What should be included under the head-
ing of leukoplakia?, 2) the development of an im-
proved definition, and 3) a classification of oral
precancer.
With regatd to what should be included under
the heading of leukoplakia, there was extensive de-
bate during which most members of the seminar
came to agree that there were probably four groups
of white lesions that could usefully be distinguished,
1, Those occurring as part of a known disease, such
as lichen planus or discoid lupus erythematosus,
2, I hose associated with and thought to be due to
the use of tobacco.
Trealment
Ren\aik needs
None
For observation 1. Observation
2. Habit intervention
.3. Yearly follow-up
1. Investigation
2. Habit intervention
fibiosis .3. Surgical, topical intervention
4. Rigorous follow-up
For therapy Surgery/radiotherapy/chemotherapy
148 AXELL, HOLMSTRUP, KRAMER, PINDUORG & SHEAR
3, Those with identifiable local cause such as fric-
tion, or dental restorations (galvanism),
4, Those which were "idiopathic" or "cryptogenic".
Attempts to resolve the other two points were
postponed to a later stage in the proeeedings,
SESSION III
Discus.non on histotogic changes associated wilh white te-
sions. A critical evaluation based on aspects of epithelial
dysplasia and carcinoma in situ.
The session was opened with a review by I. R,
H, KRAMER on "Epithelial dysplasia of the oral
mucosa," He compared his own 13 components of
epithelial dysplasia with the six components of A,
BuRKHARDT and co-workers. He preferred the term
"reduction of cellular cohesion" to "lack of cellular
adherence" and suggested that the term "dyskera-
tosis" should be discarded because to some authors
it was synonymous with epithelial dysplasia whilst
to other authors it was synonymous with intraepi-
thelial keratinization.
He further emphasized the difficulty in assessing
epithelial dysplasia objectively and presented a
series of analyses of the variations in assessment
when the members of a panel of 12 experienced
observers examined sections from the same series of
oral mucosai biopsies. He felt that there was still a
widespread and unjustified belief that the assess-
ment of epithelial dysplasia is an accurate and re-
producible process, and he welcomed the increasing
recognition ofthe problems of observer variation.
As a further step towards the reduetion of this
variation, he suggested an updating of the criteria
proposed in SMITH & PINDBORG'S "Histological gra-
ding of oral epithelial dysplasia by the use of photo-
graphic standards" and the use of computer-based
calculations to replaee the subjectively-derived
weighting factors for the individual components of
dysplasia,
KRAMER also suggested that it was important to
develop mathematical models that were not based
on an assessment of epithelial dysplasia alone, but
included clinical findings and all other relevant
data. He proposed that this work should start now,
with the preparation of a protocol for a multicentre
and international prospective study.
The problem of grading epithelial dysplasia was
discussed in the presentation "A eritical evaluation
of epithelial dysplasia in oral mueosal lesions using
the SMITH-PINDBORG method of standardization" by
M, SHEAR,* who studied 214 cases of epithelial dys-
plasia. The three most frequently registered features
in lesions diagnosed as severely dysplastic were:
mitotic activity superficial to basal layer (98%),
increased nucleo-cytoplasmic ratio (85%) and in-
creased mitotic activity (84%), Half of all lesions
involving the floor of mouth and oropharynx were
severely dysplastic, whereas most lesions occurring
in buccal and alveolar mueosa/gingiva were mildly
dysplastic; however, differences were not significant-
ly different. SHEAR eoneluded that the use of a
procedure such as the SMITH-PINDBORG system is
extremely valuable for purposes of standardization.
However, the question of whether the weighting of
the different characteristics proposed by SMITH &
PINDBORG is sufiiciently aecurate, or whether it is
too subjective, should be tested. Similarly, it is
important to test whether the histological criteria
now used to assess the severity of dysplasia are, in
fact, those which are ofthe greatest value in predict-
ing the potential for malignant change.
This problem was addressed in another contribu-
tion, "Epithelial dysplasia immediately adjacent to
oral squamous carcinomas and the relationship to
smoking," In this paper M, SHEAR** studied epi-
thelial dysplasia from a somewhat different perspec-
tive. The basis for this approach was that oral squa-
mous cell carcinoma is very frequently preceded
by a precancerous lesion and established squamous
carcinomas ofthe mouth are very often surrounded
by leukoplakia, erythroplakia or both. They there-
fore studied the histologieal features of the epithel-
ium adjacent to the neoplasm, looking for any
dysplastic features which could be regarded as pre-
dictors of malignant change, Dysplastic characteris-
tics present in more than 80% of cases were basal
cell hyperplasia and disturbed epithelial matura-
tion. Changes in adjacent epithelium were fre-
quently multicentric. The feature referred to as ba-
sal cell hyperplasia appears, in faet, to represent
disturbed epithelial maturation. In the great major-
ity of cases, increased nucleo-eytoplasmic ratio ap-
pears to result from a deerease in cytoplasmic volu-
me rather than increased nuclear size,
L, HANSEN*** suggested a new eoncept of a con-
tinuum of different lesions ranging from a simple
* Coauthor H. KATZ.
** Coauthor A. WRiGirr.
*** Coauthors J. OLSON and S. SILVERMAN ]R.

orthokeratosis to squamous cell carcinoma. He pro-
posed the term proliferative verrucous leukoplakia.
He did not exclude the possibility that lesions may
arise in different stages of the continuum,
A, LARSSON discussed the process of keratinization
as the most prominent feature in oral leukoplakia.
He suggested future enzyme-histochemical studies.
In the subsequent discussion thete was general
agreement on the need for a more objective assess-
ment of epithelial dysplasia. The group endorsed
unanimously KRAMER'S suggestion for an interna-
tional approach to the problem and urged the pres-
ent Collaborative Centre in Copenhagen to take
the initiative.
It was etnphasized that follow-up studies are man-
datory to test a revised assessment of epithelial dys-
plasia, although it was recognized that such studies
may present ethical problems.
The group had reservations about the introduc-
tion of new terms such as proliferative verrucous
leukoplakia,
SESSION IV
The signiftcance of aetiological factors for leukoplakia and
related lesions with .special reference to maiignanl potential.
J, BANOGZY opened the session and showed that,
in the population that she had studied, carcinoma
developed in 6% of patients with oral leukoplakia
and in 0,4% of patients wilh oral lichen planus.
After illustrating the importance of systemic condi-
tions such as ,sideropenic dysphagia, she listed a
variety of aetiological factors that appeared to be
of importance in the development of leukoplakia
and carcinoma. Smoking was associated with 83%
of leukoplakias and with 77% of earcinomas, Candi-
dal infection was also common in patients with car-
cinoma, but was not quite so common in the total
leukoplakia group. However, in the different clinical
types of leukoplakia, the erosive group showed a
similar high ratio of candidal infection, as the carci-
noma group did. Other factors that seemed to be
important were mechanical irritation (including the
wearing of dentures), galvanic factors, and alcohol
addiction (which was found in 33% of patients with
carcinoma but in only 13% of the patients with
leukoplakia),
P, GUPTA spoke on "A study of dose-response
relationship between tobacco habits and oral leuko-
plakia," By ineans of statistical analyses of data from
Oral leukoplakia and associated tesions 149
over 12000 individuals, he showed that there is
evidenee for a relationship between leukoplakia,
smoking, and the chewing of tobacco in pan. Both
types of tobacco usage showed a dose-response
relationship; the relationship to leukoplakia was
stronger for smoking than for chewing, and stronger
still when the individual had both habits,
GUPTA then presented a similar study on "The
relationship between oral leukoplakia and use of
alcohol," He pointed out that, in this study, only
tobacco users were included because it was believed
that an alcohol habit alone was not important. It
had not been possible to obtain information on the
amounts of alcohol consumed, atid the study was
based on frequency of usage. The results indicated
that leukoplakia was most common among those
who both smoked atid were regular consumers of
alcohol.
In the discussion following these papcis, J. BANO-
GZY agreed that some of the factors about which
she had spoken might be associated with leukoplakia
rather than causative. There was much discussion on
galvanic lesions: AXELL emphasized that electric
current might be more important than potential
difiierences between the dissimilar metals, and there
was general agreeiTient thai no clear evidence ex-
isted to justify regarding galvanic lesions as precan-
cerous, Unle,ss a galvanic cause was proven, the
term "galvanic lesion" should be avoided and the
lesion be recorded as "associated with a dental res-
toration," There was also debate on the question
oi reversibility of varioits lesions, including those
associated with dental restorations and wilh smok-
ing. Most participants considered that many such
lesions passed through a reversible phase to an irre-
versible state, but that the latter did not mean that
there would necessarily be a progression lo carcino-
ma.
In relation to the reversibility (or non-reversibil-
ity) of "frictional keratosis," A, BURKHARDT pointed
out that, whilst friction alone probably would not
predispose to carcinoma, it might promote carcino-
genesis if there were some other initiating factors.
In sumtnarizing the discussion, M, SHEAR under-
lined the general agreemetit that smoking was piob-
ably the most important aetiological factor in leuko-
plakia, and that in sotne countries the use of tobacco
in pati chewing was also important. The use of
alcohol alone seemed to be less important, but there
is some evidence that the use of tobacco together
with the cotisumplioti of alcohol causes more lesions
150 AXELL, HOLMSTRUP, KRAMER, PINDBORG & SHEAR
than either habit alone. Attention was also drawn
to the evidence that many leukoplakias will resolve
if the patient stops smoking,
P, HOLMSTRUP* described a study on "Leuko-
plakia and candidal infection" based upon a series
of patients with chronic multifocal candidosis. The
criteria for including patients in the study were
strictly defined, and all patients were re-examined
after 6 and 12 months. All of the patients were
smokers, and although treatment was never
withheld, it was believed that unless the patient
could be persuaded to stop smoking, the treatment
was not likely to prevent recurrence.
Lesions that were mainly erythematous probably
represented the mildest type, and treatment resulted
in the restoration of a clinically normal appearance.
Lesions that were of the plac[ue type reverted to
a clinically normal appearance, following treat-
ment, in about half of the cases. In contrast, lesions
that initially appeared nodular never showed total
regression. So far, no patient in this series has devel-
oped a carcinoma.
HOLMSTRUP** then spoke about "Lichen planus
as a precancerous condition," He emphasized the
initial and at present insuperable diagnostic prob-
lem ari,sing from the fact that lichen planus has no
speeifie clinical or histopathological features. It was
also noted that the plaque type of lichen planus is
more common in smokers. It seemed that carcinoma
seldom occurs in clinically "typical" lichen planus,
but that there is a greater risk in the clinically
atypical cases and especially in elderly patients with
oral lichen planus a,ssociated with areas of erythro-
plakia. HOLMSTRUP also stressed his impression that
there was a risk of carcinoma arising in atrophic
lichen planus lesions occurring on the lateral border
ofthe tongue. However, he agreed that the series of
cases on which this view was based was rather small,
'Fhere was considerable discussion about the
nature ofthe apparent relationship between certain
forms of oral lichen planus and the development of
carcinoma, HANSEN emphasized the imjjortancc of
considering the mathematical probability of coinci-
dence rather than cause and effect.
In eoncluditig the session, the Chairman empha-
sized the strong evidence for a synergistic relation-
ship between tobacco usage and oral candidal infec-
* Coauthor M. ISKSSERMANN.
** Coauthor j . PINDBORG.
tions, and the evidence that HOLMSTRUP had pre-
sented on the difference in reversibility of candidal
infections with varying clinical appearances. Re-
garding lichen planus, it was clear that cases in
which areas of erythroplakia developed were more
likely to proceed to carcinoma, whilst atrophic le-
sions of the lateral border of the tongue might also
present a risk,
SESSION V
The .significance of location and the clitiical morplwlogy of
oral white precancerous lesions for the prognosis.
I, KRAMER opened the session with a presentation
on "Sublingual keratosis," He pointed to the par-
ticularly high risk of malignant transfortnation of
these lesions and further elucidated those clinical
features which were signifieanlly correlated with
present or future development of cancer. The clini-
cal features related to an existing malignant change
in the sublingual lesion were the simultaneous pres-
ence of white and red areas, red areas alone, ulcera-
tion, and spontaneous symptoms. The presence of
a nodular pattern was significantly related to malig-
nant change at some time in the future,
1, VAN DER WAAL spoke on "Leukoplakia and
associated lesions of the tongue" emphasizing that
of the various premalignant lesions alfecting the
tongue the leukoplakias are the most common. Of
all oral leukoplakias less than 10% are located on
the tongue. Malignant transformation apparently
occurs more frequently in leukoplakias ofthe tongue
than other sites, with a possible exception for leuko-
plakias of the floor of the mouth. Malignant
transformation seems most likely to oeeur in the so-
ealled idiopathic leukoplakia, Erythroplakia rarely
affects the tongue as a "pure" lesion. When it does
occur, the biopsy usually will reveal dysplastic or
malignant changes.
Median rhomboid glossitis is not considered to be
a premalignant lesion, A few cases of carcinoma
arising in the area ofthe foramen caecum have been
reported in the literature. However, in none of those
cases was there evidence of a preexisting median
rhomboid glossitis. Furthermore, on reevaluation of
the histological material, there was serious doubt
about the diagnosis of carcinoma in a number of
those cases.
VAN DER WAAL also referred to problems arising
with commissural lesions, and particularly to the

difficulties (both clinical and histological) in distin-
guishing benign from malignant lesions,
L, SoBiN gave an overview of "Precancerous le-
sions ofthe digestive tract,"
In the subsequent general discussion it was agreed
that the term sublingual keratosis was tiot the best
choice, 1 he group felt that the term .mblittgtial leuko- 89%
plakia would be more appropriate; leukoplakia is a
clinically descriptive term, whilst keratosis is based
on histological findings. There was agreement that
lesions in the floor of the mouth are particularly
dangerous, and it was also noted that lesions of this
type are rare in Asia,
L, HANSEN commented that commissural lesions
demonstrated by the Dutch and the Danes as rather
prevalent in their countries are very rare in the
United States,
T AXELL confirmed the observation that commis-
sural lesions are prevalent in Sweden, but that the
nodular type of lesion is very rare,
S, WARNAKULASURIYA added that commissural
lesions are common among Sri Lankan men, par-
ticularly bidi smokers, and a large majority ol these
lesions are nodular.
There was considerable discussion about the
problem of epithelial dysplasia a,ssociated with can-
didal infection. Some participants believed that
such changes were not an expression of a malignant
potential, whereas others eonsidered them to be
"true" dysplasias, although possibly of a reversible
natuie.
SESSION VI
The significance of epidemiological studiesfor the evaluation
of clinical risk groups and lhe planning of preventive meas-
ures.
S, WARNAKULAsutiiYA pointed out that studies in
India had showti that oral caticer was almost always
preceded by some form of precancerous lesion and
that there was a definite relationship between such
lesions and both smoking and chewing of betel quid
with tobacco.
Individuals at risk for the development of oral
cancer in Southeast Asia are therefore those who:
1) have a precancerous lesion and 2) smoke or chew
betel nut with tobacco, Bidi smoking, commonest
among men, is also an important lactoi.
In order to screen "at i isk" populatiotis an early
detection programme was instituted in Sri Lanka
Orat teukoptakia and associated Ies. 151
on a sample of 87277 subjects in a population of
164000 in a study area of 67 square miles, using 35
health workers. In the first year, one third of the
population had been screened; 1222 patients with
lesions had been identified and 614 of these had
attended centres to which they had been referred,
of these needed attention. At the referral cen-
tres, the provisional "field" diagnosis was confirmed
in 73% of the cases. Of significance was the fact
that the primary health workers showed a greater
enthusiasm, and a higher degree of accuracy, than
physicians and dentists involved in a hospital based
study carried out in an adjacent health area,
P, GUPTA reported on "Preventive programmes
for reduction of aetiological factors and for the early
detection of oral cancer in India," a study similar
to the Sri Lankan study, A pritnary prevention pro-
gramme (for reduction of aetiological factors for
oral cancer) and a secondary programme (for early
detection of oral cancer) had been instituted. The
primary prevention programme had already re-
sulted in a considerable reduction of tobacco habits.
In the secondary programme basic health workers
were used to identify and refer the high risk group
ol individuals over 35 years of age who had lesions
such as nodular leukoplakia, submucous fibrosis, or
an ulcer,
ZHANG KUI-HUA gave a paper on "An epidemiol-
ogical survey or oral leukoplakia in 134492 inhabit-
ants from certain districts of China," and the results
were summarized as follows:
Prevalence of lenkoplaki a in China
No. No. with
leukoplakia Pre\alencc
examined
Men 88668 (65.93%) 13104 14.78%
Women 45824 (34.07%) 969 2.11 "o
1.34492 100.00 14073 10.4(3",,
Of considerable interest was the fact that in this
Chinese sample, only seven lesions occurred on the
margins ofthe tongue, four on the ventral surface,
and six on the floor ofthe mouth (0,03%), A higher
proportion of leukoplakias were found in han yen^
smoket-s than in cigarette stnokers. None ofthe leu-
koplakias were associated with malignancy.
Han yen lobacco is a speeiai strong tobacco u.sed in pipes.
152 AXELL, HOLMSTRUP, KRAMER, PINDBORG & SHEAR
The high prevalence rates of leukoplakia in China
may be attributable to the inclusion of cases of
smoker'.s palate and prelcukoplakia.
During the discu,s.sion, the question was posed as
to whether there might be intrinsic differenees in
the nature of the mucosa of the floor of the mouth
which might render some populations more suscep-
tible than others to floor of mouth dysplasias and
cancers.
The session ended with a paper by J, STJERNS-
WARD, from the WHO Cancer Unit, on "The im-
portance of standardized eoneepts, criteria, and of
calibration in epidemiological work aiming at pre-
ventive measures and programmes." He empha-
sized the need for the pooling of resources to increase
the amount of material available for the study of
oral precancer. What WHO needs is a useful classifi-
cation and a good guideline manual.
The group agreed that a manual would be desir-
able, but that aspect was not included in the objec-
tives for the Meeting,
SESSION VII
The significance of advanced methods (histochemical, ultra-
structural, immunological, experimental'approach, etc.) for
the prognosis of oral leukoptakia.
A, BURKHARDT presented a review on "Methods
for the evaluation of oral premalignant lesions and
carcinomas," partly based on personal experienee,
and partly on data from the literature. He discussed
exfoliative cytology, quantification of histopathol-
ogy, cell kinetics, histochemistry, enzyme histochem-
istry, immunohistochemistry and electron micro-
scopy. He concluded that at present none of those
methods is of great value in the quantification of
epithelial dysplasia or in assessing with confidence
the biological behaviour of a lesion ofthe oral mueo-
sa.
In the discussion members ofthe group described
similar experiences with some of these methods,
J, BANOCZY presented the results of transmission
and scanning microscopical examinations in various
clinical types of leukoplakia. Although there was
some correlation between the clinical and labora-
tory findings, the methods were not felt to be of
major importanee in the clinical and histological
diagnostic aspects of oral leukoplakia,
P, HOLMSTRUP* presented a paper on "1 he rever-
sibility of leukoplakia in an experimental model,"
The results obtained from the grafting of human
oral tissues to nude mice support the concept of the
existence of two different types of leukoplakia, one
possessing an irreversible pattern of epithelial kerati-
nization, the other showing reversibility. The chan-
ges were demonstrated after an experimental period
of 3 weeks, which is a shorter period than that
necessary in clinical studies to demonstrate reversi-
bility.
HOLMSTRUP suggested that the irreversible lesions
are probably autonomous processes representing a
true premalignant potential, whereas the reversible
lesions may be regarded as physiological reactions
to trauma such as tobacco,
1, KRAMER discussed the "Carcinoetnbryonic an-
tigen" (CEA) and the more recently-described "car-
cinoma antigen" (Ca) in oral mucosai lesions. It
was empha.sized that the anti-CEA sera as obtained
eommercially may contain a wide range of com-
ponents which have obscured the results obtained
so far. When antibodies to normal eross-reacting
antigens (NCA) were removed, oral earcinomas
gave negative results with the absorbed serum,**
The Ca antigen was first described in 1982, and
the monoclonal anti-Ca antibody is termed Ca 1,
Using an immunoperoxidase technique, it was
found*** that most oral squamous cell carcinomas
gave positive reactions with Ca 1, although the
results varied both in intensity and in the numbers
of cells labelled. However, the epithelium of a wide
variety of non-neoplastic oral lesions also gave a
positive reaction, and it was concluded that Ca 1
was not likely to be ol mueh diagnostic or prognostic
value in the assessment of lesions or oral mucosa,
M, SHEAR summarized this session by mentioning
that, whilst at present histochemical and immuno-
logical methods do not seem to be very promising
in identifying precancerous lesions, it is important
that this type of research should be continued,
SESSION VIII
During the final session, mueh ofthe discussion was
on the problems of terminology and classification.
All participants agreed on the importance of stan-
dardized definitions, because without such stan-
dardization the results of different studies or surveys
* Coworkers E. DABELSTEEN and B. ROED-PETERSEN.
** Coworkers L. IVANYI and C. T. KWA.
* * * Coworkers H. SIIAHANA and L. IVANVI.

can not be related to one another. Earlier in the
present conference, there had been clear examples
of variations in definitions, with the result that some
sets of data could not be compared with confidence.
If definitions and classifications are to be pre-
pared that can receive gctieral acceptance, there
must be recognition of existing dilTerences in con-
cepts and terminologies. The proposals that follow
received a large measure of approval from the mem-
bers of the conferenee, and they are recommetided
for general use. Some have previously been pub-
lished, and for these appropriate referenees are
given.
It should be emphasized that the individual types
of lesions mentioned here are intended as illustrative
examples, rather than to provide a complete and
eomprehensive listing. It should also be noted that
these lesions vary greatly in their probability of
malignant change, and that this variation appears
to depend on many factors including location.
Therefore, it is essential to refer to more comprehen-
sive works for information about the risks associated
with particular lesions or conditions.
DEFINITIONS AND GUIDELINES
Precancerous lesion
A morphologically altered tissue in which cancer is
more likely to occur than in its apparently normal
counterpart,^ Examples of precancerous lesions are
leukoplakia and erythroplakia,
Precancerous condition
A generalized state associated with a signifieantly
increased risk of cancer, Exatnples of precancerous
conditions are sideropenic dysphagia and, possibly,
lichen planus,
Leukoplakia
Leukoplakia is a whitish patch or plaque that can-
not be characterized clinically or pathologically as
any other disease and it is not associated with any
physical or chemical causative agent except the use
of tobacco.
This definition is based upon the one proposed
by WHO,^'' The relationship to the use of tobaeco is
also mentioned in the aetiological description given
below.
'f Report from a WHO "Meeting of Investigators on lhe Hislo-
logical Definition of Precaucerous Lesions," 1972.
I^t Oral Surg 1978; 46: 518 39.
Oral leukoplakia and associated le.sions 1 53
Erythroplakia
The term erythroplakia is used analogously to leu-
koplakia to designate lesions ofthe oral mucosa that
present as bright red patches or plaques that cannot
be characterized clitiically or pathologically as any
other condition,
A complete description of n precancerot/s lesion (e,g,
leukoplakia and erythroplakia) comprises aetiologi-
cat, clinical, topographical, and histotogicat characteris-
tics. These characteristics were discussed only as
related to leukoplakia,
1. Aeliologicat description
Over the years the term leukoplakia has been used
for lesions havitig a whitish appearance as the com-
mon denominator. However, studies indicate that
whitish lesions have a widely different aetiological
backgtound. Since the premalignatit potential may
be related to aetiology it is important to describe
aetiological factors,
a) Lesions that are of unknown aetiology should be
listed as idiopathic (or cryptogetiic) leukoplakias,
b) Whitish patches or plaques associated with, and
thought to be result from, the use of tobacco
should be listed as tobacco-associated leukopla-
kias,*
c) Whitish patches or plaques for which a local
cause other than the use of tobacco can be iden-
tified should be listed according to the known
cause and tiot be termed tetikoptakias. Examples are
frictional lesions, lesions associated with dental
restoratiotis, lesions associated with cheek-biting,
2. Clinical description
The clinical subdivision of precancerous lesions has
important implications for prognosis. It is generally
agreed that the homogeneous leukoplakia carries
the lowest risk of malignant transformation, whilst
non-homogeneous forms, mixed red- and whitish
lesions and pure erythroplakias carry a higher risk,
a) Homogeneous leukoplakia (simplex)
A uniformly whitish lesion with a smooth or
corrugated surface,
b) Non-hotnogeneous leukoplakia
i) Erythroleukoplakia (erosive leukoplakia),
A whitish lesion that includes red areas.
* The eondition known as leukokcratosis nieotina palati is so
distinctive that it .should continue to be listed separately. How-
ever, the lesion is probably not caused by nicotine, and the term
"smoker's palate" is preferred.
154 Axi^:LL, HOLMSTRUP, KRAMER, PINDBORG & SHEAR
ii) Nodular leukoplakia. A lesion with slightly
raised, rounded, red atid/or whitish excres-
cences that may be described as granules or
nodules,
iii) Verrucous leukoplakia. An exophytic lesion
with irregular sharp or blutit projections,
NB, Erythroleukoplakia and the nodular
type of leukoplakia are also referred to as
speckled leukoplakia or as speckled erythro-
plakia,
Erythroleukoplakia and the nodular leuko-
plakia are in most instances associated with
candidal infection,
3. Topographical description
The location ofthe lesion is regarded as important,
because apparently similar lesions in different oral
sites may carry different tisks of malignant change.
For example, leukoplakia in the floor ofthe tnouth
appears to carry a particularly high risk. It is recom-
mended that records of site should normally be
based on the sites indicated in "Application of the
International Classification of Diseases to Dentistry
and Stomatology" (WHO 1978) in the sections
140-145,*
4. Histological descriptitm
The microsco|3ical appearances of precancerous le-
sions have been discussed by WHO** and in many
other publications. It should again be emphasized
that leukoplakia is a clinical term, and its use carries
no implications with regard to the histological find-
ings. However, it is recommended that a histological
report should always include a statement on the
presence or absence of epithelial dysplasia and, if
present, an assessment of its severity.
* If more detailed records of intraoral site are re(|uired, tbc
topography ])roposed by ROED-PETF.RSKN & RENSIUIIP [Ada
Oilontol Seand 1969; 27: 681-95) may be used.
** Orat Sttrg 1978; 46: 518 39.