Critical Reviews in Oral Biology & Medicine

http://cro.sagepub.com

ORAL LICHEN PLANUS AND MALIGNANT TRANSFORMATION: IS A RECALL OF PATIENTS JUSTIFIED?

Ulf Mattsson, Mats Jontell and Palle Holmstrup
Crit. Rev. Oral Biol. Med. 2002; 13; 390
DOI: 10.1177/154411130201300503

The online version of this article can be found at:

http://cro.sagepub.com/cgi/content/abstract/13/5/390

Published by:

http://www.sagepublications.com

On behalf of:
International and American Associations for Dental Research

Additional services and information for Critical Reviews in Oral Biology & Medicine can be found at:

Email Alerts: http://cro.sagepub.com/cgi/alerts

Subscriptions: http://cro.sagepub.com/subscriptions

Reprints: http://www.sagepub.com/journalsReprints.nav

Permissions: http://www.sagepub.com/journalsPermissions.nav

Downloaded from http://cro.sagepub.com by on June 26, 2010

 CONTROVERSY
Lichen planus is a dermatological disorder that can have oral manifestations prior to skin involvement. The pre-malignant poten-
tial of oral lichen planus has been a controversial issue for the past several decades. Some of the controversy can be attributed to the
fact that several studies have focused on the development of oral cancer in cohorts of patients with oral lichen planus diagnosed on
the basis of different criteria and followed for various periods of time. This article by Mattsson, Jontell, and Holmstrup is a critical eval-
uation of the pre-malignant potential of oral lichen planus and its consequences for the clinical management of this disorder.
–Olav Alvares, Editor

ORAL LICHEN PLANUS AND MALIGNANT

TRANSFORMATION: IS A RECALL OF PATIENTS JUSTIFIED?
Ulf Mattsson1,2
Mats Jontell2
Palle Holmstrup3*

1Clinic of Oral and Maxillofacial Surgery and Hospital Dental Care, Central Hospital, Karlstad; 2Clinic of Oral Medicine, Faculty of Odontology, Göteborg University, Sweden; and 3Department

of Periodontology, School of Dentistry, University of Copenhagen, Denmark; *corresponding author, [email protected]

ABSTRACT: There has been a continuous debate regarding the possible malignant potential of oral lichen planus (OLP). Based
on the results from follow-up studies, OLP is regarded by several authors as a pre-malignant condition, and patients with OLP
have been recommended to have their lesions monitored two to four times annually. This recommendation needs reconsidera-
tion, because a recall system of all patients with OLP requires substantial economic resources. In a reality where such resources
are limited, a recall system must be weighed against other benefits and the fact that the malignant potential of OLP is most like-
ly very low. The present review focuses on the diagnostic criteria for OLP, the pre-malignant potential of OLP, and the extent to
which the available information can be used to reduce morbidity and mortality of oral cancer related to OLP.

Key words. Oral cancer, lichenoid dysplasia, diagnostic criteria, prognosis, oral mucosa, lichen planus, prevention.

Introduction Krutchkoff and Eisenberg have stated that some of the report-
ed OLP cases developing oral cancer were in fact not OLP, but

S everal prospective (Holmstrup et al., 1988; Silverman et al.,

1991) and retrospective studies (Warin, 1960; Altman and
Perry, 1961; Janner et al., 1967; Abramova, 1968; Andreasen,
rather dysplastic lesions with lichenoid features. The implica-
tion of this premise is that patients with lichenoid dysplasia
represent a risk group which can be identified by the appropri-
1968; Cawson, 1968; Shklar, 1972; Fulling, 1973; Kovesi and ate use of available diagnostic methods and, as such, can be
Bánóczy, 1973; Holmstrup and Pindborg, 1979; Vas’kovskaia distinguished from patients with OLP with no dysplasia-relat-
and Abramova, 1981; Silverman et al., 1985; Murti et al., 1986; ed increased risk of development of oral cancer.
Salem, 1989; Sigurgeirsson and Lindelof, 1991; Voute et al., Since OLP is considered a pre-malignant condition by sev-
1992; Barnard et al., 1993; Brown et al., 1993; Moncarz et al., eral authors, a recall system for OLP patients has been recom-
1993; Duffey et al., 1996; Markopoulos et al., 1997; Silverman mended to facilitate the early diagnosis of oral cancer with the
and Bahl, 1997; Lo Muzio et al., 1998; Rajentheran et al., 1999) aim of reducing morbidity and mortality from oral cancer ari-
as well as case reports (Faraci et al., 1975; Marder and Deesen, sing in OLP patients. One suggestion is that OLP patients
1982; Pogrel and Weldon, 1983; Fowler et al., 1987; Katz et al., should have regular follow-up examinations from two to four
1990; Massa et al., 1990; Harland et al., 1992; Porter et al., 1997; times annually (Scully et al., 1998). Since OLP is one of the most
Camisa et al., 1998; Chainani-Wu et al., 2001) have reported prevalent oral mucosal lesions, a recall program demands sub-
oral lichen planus (OLP) as having an increased potential for stantial economic resources, and hence, a reconsideration of the
malignant development. The reported transformation rates background of the need for a recall is warranted.
vary from 0 to 9%. Several studies have been conducted An established recall system must be based on two impor-
recently, and there is a need for an updated review to re-assess tant basic assumptions:
available information to arrive at proper guidelines for the (i) It is possible to identify patients with an increased risk of
management of OLP. cancer development; and
The issue of a malignant potential of OLP has been a mat- (ii) it is possible to reduce cancer morbidity and/or mortality
ter of serious controversy (Krutchkoff et al., 1978; Krutchkoff as a result of the recall program.
and Eisenberg, 1985, 1986; Holmstrup, 1992; Eisenberg, 2000). These assumptions will be addressed below.

390 Crit Rev Oral Biol Med 13(5):390-396 (2002)

Downloaded from http://cro.sagepub.com by on June 26, 2010
TABLE
Studies on the Relationship between Oral Lichen Planus (OLP) and Oral Cancer

No. of
Histological Oral Follow-up
Confirmation No. of Cancer Period (mean
Author(s)/Year Type of Study of OLP OLP Patients Gender Cases % and/or range) (yrs)

Holmstrup and Pindborg, 1979 Retrospective Yes 740 Unknown 3 0.4a 0.4-6.5
Silverman et al., 1985 Retrospective Yes 570 384F, 186M 7 1.2 5.6
Holmstrup et al., 1988 Prospective Yes 611 409F, 202M 9 1.5 1-26
Salem, 1989 Retrospective Yes 72 40F, 32M 4 5.6 3.2
Silverman et al., 1991 Prospective Yes 214 152F, 62M 5 2.3 9
Barnard et al., 1993 Retrospective Yes 241 Unknown 9b 3.7 0.5-17
Duffey et al., 1996 Retrospective Yes 955 Unknown 5 0.5 4.25
Markopoulos et al., 1997 Retrospective Yes 326 239F, 87M 4 1.3 6.5
Lo Muzio et al., 1998 Retrospective Yes 263 156F, 107M 14 5.3 3-10
Rajentheran et al., 1999 Retrospective Yes 832 Unknown 7c 0.8 1-9
Mignogna et al., 2001 Retrospective Yes 502 311F, 191M 24 4.8 0.4-12

a Eight patients with simultaneous oral lichen planus and erythroplakic lesions were followed at regular intervals. Two of eight patients with erythroplakia
demonstrated severe dysplasia and oral cancer at initial examination. One patient developed oral cancer during the follow-up period.
b Eight patients developed invasive carcinoma and one patient carcinoma in situ.
c Four of the seven cases were carcinoma in situ.

(i) Identification of Patients with Increased the oral mucosa. In addition to these features, plaque-type, atrophic,
Risk of Cancer Development ulcerative, and bullous lesions may be present at the time of diagno-
sis, or they may occur during the course of the disease (Thorn et al.,
Several studies have attempted to establish the risk of cancer
1988). None of these latter types of features is limited to OLP, and
development in OLP patients. Based on their design, the avail-
consequently they are not well-suited to distinguish OLP from other
able studies may be divided into case reports, retrospective,
diseases. The presence of reticular white striations and/or papules
and prospective follow-up studies. Case reports are of limited
was an inclusion criterion in all 11 studies in the Table.
value and are not further considered in the present review.
The histopathologic features of OLP include several
Retrospective studies often entail incomplete data, since the
epithelial changes, the amount and extension of which vary.
patient materials are selected after termination of the observa-
Epithelial hyperkeratosis, atrophy or hyperplasia, acantosis,
tion period, and the information available is not defined prior
saw-toothed rete ridges, liquefaction degeneration of basal
to the examinations and follow-ups of the patients. In an effort
cells, and single-cell keratinization are all prominent charac-
to base a discussion on studies with the most uniform and
teristics. A homogeneous cell-free zone is frequently present in
accurate information, the present review is restricted to the 2
the basement membrane zone. The subepithelial connective
prospective and 9 retrospective studies in which the diagnostic
tissue shows a band-like inflammatory infiltrate dominated by
criteria have been defined (Table).
lymphocytes and macrophages (Andreasen, 1968).
Biopsy is obviously an important tool in the diagnostic process
THE DIAGNOSTIC DILEMMA OF OLP for OLP (Barnard et al., 1993), but a diagnosis of OLP based solely
The ongoing debate includes a question on what is “true OLP” on histopathology in some cases leads to an erroneous result.
(Eisenberg, 2000; Silverman, 2000). We are not sure that any type Misinterpretation by the pathologist may also be a source of error.
of disease entity can be “true”, because a disease entity is not a Eisenberg and Krutchkoff (1992) have stated that some reports
living organism acting “truly” or “falsely”. Disease processes are have shown microphotographs suggestive of diagnoses other than
always modified by factors dependent on the single individual OLP. Whether or not this comment is justified is a matter of debate,
affected. If, on the other hand, diagnostic criteria are regarded as but it emphasizes the well-known problem of subjectivity resulting
important tools for handling groups of patients, it is important to in intra- and interindividual variation among pathologists (van der
focus on whether patients included in studies of the pre-malig- Meij et al., 1999a). Some diagnoses, such as, for example, lichenoid
nant nature of OLP fulfilled explicitly defined diagnostic criteria. contact reactions (LCR) caused by components released from amal-
They did so in the 11 studies mentioned in the Table. These stud- gam fillings, are impossible to distinguish from OLP histopatho-
ies involved OLP patients diagnosed on the basis of both clinical logically (Bolewska and Reibel, 1989). Since these lesions are not
and histopathological criteria. known to be associated with malignant transformation, their inclu-
It is widely approved that the most characteristic clinical feature sion may result in a decrease in the rate of malignant potential of
of OLP is the presence of reticular white striations and/or white OLP. However, such lesions can be distinguished on the basis of
papules, essentially distinguishing the disease from other diseases of clinical criteria (Bolewska et al., 1990; Bratel et al., 1996).

13(5):390-396 (2002) Crit Rev Oral Biol Med 391

Downloaded from http://cro.sagepub.com by on June 26, 2010
 In the reported studies, were patients with dysplastic staining was questioned in the recent study by Mignogna et al.
lesions in fact included in the risk analysis, thereby overstating (2001). It remains to be shown if these methods can be used as
the risk of malignant transformation of OLP? For obvious rea- prognostic tools to identify OLP patients susceptible for future
sons, this question cannot be fully answered, but most of the squamous cell carcinoma (SCC) development.
studies have been conducted by investigators with acknowl- Thus, several histological markers have been examined or
edged expertise in oral medicine and oral pathology. One of proposed as prognostic factors, but, to our knowledge, there is
the prospective studies has specifically stated that if biopsies currently no specific marker that has been widely agreed upon for
showed epithelial dysplastic features, the patients were determination of a possible future malignant transformation.
excluded from the follow-up study (Holmstrup et al., 1988). It has been advocated that OLP patients with a risk of
It is most important that measures be developed for the iden- future malignant development can be identified with current
tification of the subgroup of OLP patients susceptible to the future diagnostic methods as long as the methods are used properly
development of oral cancer. The specific clinical features do not (Eisenberg, 2000). The comment stems from pathologists’
obviously shed light on the potential for cancer development, neglect in identifying epithelial dysplasia and clinicians’ reflex-
since the different types of OLP lesions developing oral cancer, as ively rendering a presumptive diagnosis of OLP on the basis of
included in the Table, showed the following distribution: reticular relatively weak and superficial clinical criteria. Improved diag-
33%, plaque 29%, atrophic 13%, and ulcerative/erosive 25%. nostic skills must, however, entail sound scientific studies
In the past, scientists have investigated several histo- based on well-defined criteria which have been evaluated for
chemical markers to determine their relevance as prognostic their prognostic value in identifying OLP patients who might
tools in the evaluation of OLP, epithelial dysplasia, and oral be at risk for the development of oral cancer.
cancer. These include altered expression of alpha9 integrin In the process of evaluating diagnostic criteria, it is essen-
(Häkkinen et al., 1999) and laminin-5 staining (Kainulainen et tial that cases with a higher potential for malignant transfor-
al., 1997). It has also been proposed that p53-positive patients mation than OLP be excluded. Although existing prospective
with otherwise benign lesions should be followed more follow-up studies vary somewhat in their diagnostic criteria,
closely (Crosthwaite et al., 1996), and similar results have their results are not very different, and they do provide a
been reported by Girod et al. (1994, 1995) implying that body of information for the evaluation of the pre-malignant
expression of mutated p53 is an indicator of potential malig- potential of OLP.
nant development in benign lesions of the oral mucosa In summary, conclusive investigations on the pre-malig-
(Girod et al., 1993). Involucrin immunoreactivity has also nant potential of OLP have been carried out as prospective or
been proposed as a method to distinguish between lichen retrospective studies of patient samples characterized on the
planus and lichenoid dysplasia (Eisenberg et al., 1987). Using basis of explicit clinical and histopathological criteria, i.e., retic-
microsatellite analysis to elucidate the pre-malignant poten- ular and/or papular lesions, and demonstrating histopatholog-
tial, Zhang et al. (1997, 2000) reported that lichenoid lesions ic features including hyperkeratosis, liquefaction degeneration
with mild dysplasia showed a higher loss of heterozygosity of basal cells, and a subepithelial band-shaped inflammatory
(54%) as compared with OLP (6%). Although the findings reaction dominated by lymphocytes and macrophages. Lesions
may reinforce the current opinion of lichenoid dysplasia as with dysplastic features should be excluded on the basis of
having a higher tendency of malignant development than their histopathology, and this has been explicitly mentioned in
OLP, this marker has not yet been evaluated as a prognostic one study (Holmstrup et al., 1988).
marker for the development of oral cancer, and the findings
do not exclude a low but significant risk for OLP patients to THE REPORTED MALIGNANT POTENTIAL OF OLP
develop malignancy. Several studies have documented a relationship between OLP
A recent study (Sudbo et al., 2001) may be an important and oral cancer (Table). In addition to the diagnostic criteria,
advance in the molecular assessment of the risk of oral cancer several aspects are important for the interpretation of the
development in patients with leukoplakia. A blinded investi- results obtained.
gation of DNA content in excisional-biopsy specimens of dys- Most studies have shown that patients with OLP develop
plastic oral leukoplakias from 150 patients who were followed oral cancer at an increased rate as compared with the general
for a mean of 8.6 yrs showed that the DNA content was a population. There are only two studies with a prospective design
powerful predictor of the risk of malignant transformation of and recall on a regular basis. In one of these (Holmstrup et al.,
the lesion. Surprisingly, the degree of dysplasia did not corre- 1988), all cases (n = 611) were histopathologically investigated
late with DNA content or the risk of cancer. Studies are war- prior to the manifestation of oral cancer. During follow-up, nine
ranted to evaluate this method as a predictor for malignant patients (1.5%: eight females, 1.9%; and one male, 0.5%) devel-
transformation of OLP lesions. oped oral cancer. At the time of initial diagnosis, the patients had
The use of test methods such as vital staining with tolui- lesions with no clinical evidence of atypical features, but seven of
dine blue and brush biopsy (cytology) may enhance the possi- the patients who developed oral cancer had plaque or atrophic
bility for the identification of signs of dysplasia or carcinoma in areas as part of the initial lesions. Interestingly, the plaque form
existing lesions (Epstein and Scully, 1997; Handlers, 2001). seemed to be overrepresented among patients developing oral
Therefore, in certain situations, they may serve as alternatives cancer, a finding consistent with findings of other studies
to biopsy in recall systems, although the value of toluidine blue (Silverman et al., 1991; Mignogna et al., 2001). As mentioned

392 Crit Rev Oral Biol Med 13(5):390-396 (2002)

Downloaded from http://cro.sagepub.com by on June 26, 2010
above, however, the studies presented in the Table do not pro- To conclude, the increased incidence of oral cancer in
vide data to conclude that any clinical type of OLP is particular- patients with OLP merits this mucosal disease to be regarded
ly prone to the future development of cancer. as a pre-malignant condition. This is of primary importance
Despite differences in experimental designs, it is striking when it comes to developing treatment strategies for patients
that the majority of studies have reported a rate of malignant suffering from OLP.
transformation of OLP between 0.5 and 2% (Table) over a five-
year period. Based on age- and gender-matched general popu- (ii) Decreased Cancer Morbidity and/or
lation data from the Cancer Registry of Denmark, it was esti- Mortality as the Result of a Recall Program
mated that patients with OLP had a 50 times higher risk of For the minimization of morbidity and mortality as a conse-
developing oral cancer than did the general population quence of malignant transformation of OLP, an early identifi-
(Holmstrup et al., 1988). For women, the risk was 70 times high- cation of oral cancer and its precursors has been considered as
er; for men, 14 times higher. Others (Barnard et al., 1993) have important (Silverman, 1992, 1993, 1994; Fossion et al., 1994;
also regarded OLP as a disorder with a potential for malignant Scully and Ward-Booth, 1995; Kabani and Dhingra, 1997; Scala
development, with the likelihood of cancer development in et al., 1997; Shugars and Patton, 1997). In that regard, recall sys-
lichen-planus-affected oral mucosa being 10 to 20 times greater tems for OLP have been proposed to include professional
than in the general population (MacDonald, 1975). In a recent examination 2-4 times annually (Moncarz et al., 1993; Duffey et
paper, a thorough evidence-based approach was used to calcu- al., 1996) or once a year (Voute et al., 1992; Barnard et al., 1993;
late the risk for OLP patients to develop oral cancer (Drangsholt Lo Muzio et al., 1998; Scully et al., 1998).
et al., 2001). The increased risk was estimated to be roughly 10 In a recent Italian study (Mignogna et al., 2001), a meticulous
times higher than that seen in the general population. examination of OLP patients at least three times a year was advo-
All studies mentioned in the Table are based on cohorts of cated to improve the prognosis of patients developing oral can-
referred patients, and, most likely, patients with symptomatic OLP cer. The study is based on 502 patients with OLP where 24 cases
are overrepresented in such cohorts. In this context, it is interest- of early oral cancer were identified during the follow-up period.
ing to note that Murti et al. (1986), in a study of the general popu- In a previous study by the same group (Lo Muzio et al., 1998), one
lation, found an incidence of oral cancer among OLP patients that examination annually of 263 patients with OLP was conducted.
was not very different from that reported in studies of referrals. With this regime, 14 cases with a more advanced form of oral can-
The prevalence of OLP in the Swedish population has been cer compared with those reported in the 2001 study were found.
estimated to be 1.89% (Axéll, 1976). In this study, which is often Surprisingly, however, the number of recurrences and the mor-
referred to in the on-going discussion, the diagnosis of OLP was talities did not differ significantly when the two studies were
mostly based solely on clinical appearance. Since the follow-up compared. Consequently, these studies indicate that frequent fol-
studies of OLP mentioned in the Table include only patients with low-ups do not automatically lead to an improved prognosis for
a diagnosis of OLP based on both clinical and histopathological OLP patients with oral cancer. A problem similar to that men-
findings, these studies are incompatible with the Swedish study. tioned above has been addressed for lung cancer, which remains
Also, in the Swedish study, there was no distinction between OLP a prevalent and deadly disease where only surgical resection of
and LCR, because LCR was not recognized as a disease entity at early-stage disease improves the prognosis for the patients (Ellis
that time. The implication of this is that the prevalence of OLP and Gleeson, 2001). The critical question is whether or not lung
may include LCR. If so, the prevalence of OLP in the general pop- cancer screening produces a measurable reduction in the mortal-
ulation may in fact be lower than reported. ity of patients being screened. Large randomized studies have
It has been concluded that if 1-2% of all OLP underwent a been conducted to answer this question. The Mayo Lung Project
malignant transformation, then OLP would be the major source of (Fontana et al., 1984, 1986) was a randomized, controlled clinical
oral cancer in many parts of the world (van der Meij et al., 1999b). trial of lung cancer screening conducted in 9211 male smokers
Van der Meij et al. found this extremely unlikely, and others have between 1971 and 1983. Those in the intervention arm were
expressed similar positions (Allen, 1998). It is reasonable to believe offered chest x-ray and sputum cytology every 4 months for 6
that the prevalence of OLP varies in different parts of the world years; those in the usual-care arm were advised, at trial entry, to
(Scully et al., 1998). Consequently, it is hazardous to predict the receive the same tests annually. Unfortunately, no lung cancer
true number of oral cancer cases associated with OLP, when the mortality benefit was evident at the end of the study. Needless to
prevalence figures of OLP in most populations are merely pre- say, follow-ups of OLP patients have little in common with
sumed or unknown. Studies in which the transformation rate has screening of lung cancer except for the fact that early diagnosis of
been established may, for several reasons, not be related to these oral as well as lung cancer undoubtedly improves the prognosis
prevalence figures, because most studies are carried out in cohorts of patients developing these forms of cancer. Obviously, the mea-
of referred OLP patients. sures taken have not been proven sufficient to reduce the mor-
In a study of patients with lichen planus of the skin, an bidity or mortality rate of patients with lung cancer or of oral can-
increased rate of oral but not skin cancer was discovered cer related to OLP. Thus, there is definitely a demand for larger
(Sigurgeirsson and Lindelof, 1991). In this connection, it is impor- randomized studies.
tant to note that studies have shown that OLP in patients with cuta- What can be done in the interim? First, it can be stated cat-
neous lichen planus (CLP) is not different clinically or histopatho- egorically that OLP entails a small but significant risk for oral
logically from OLP in patients with OLP alone (Andreasen, 1968). cancer development. However, this fact should not be used as

13(5):390-396 (2002) Crit Rev Oral Biol Med 393

Downloaded from http://cro.sagepub.com by on June 26, 2010
a justification for several examinations annually, since large Bratel J, Hakeberg M, Jontell M (1996). Effect of replacement of
resources would be spent on activities with no established ben- dental amalgam on oral lichenoid reactions. J Dent 24:41-45.
efit. Under these circumstances, it seems reasonable to exploit Brown RS, Bottomley WK, Puente E, Lavigne GJ (1993). A retro-
existing resources where patients encounter health care profes- spective evaluation of 193 patients with oral lichen planus. J
sionals. As an example, in Scandinavia, more than 90% Oral Pathol Med 22:69-72.
Camisa C, Hamaty FG, Gay JD (1998). Squamous cell carcinoma
(Hugoson et al., 1995) of the adult population visit a dentist on
of the tongue arising in lichen planus: a case report and review
a regular recall basis, which provides an obvious opportunity of the literature. Cutis 62:175-178.
for regular screening of the oral mucosa. Several authors have Cawson RA (1968). Treatment of oral lichen planus with
also advocated that other dental care workers should play a betamethasone. Br Med J 1:86-89.
role in detecting oral cancers (Leong et al., 1995; Alvi, 1996; Chainani-Wu N, Silverman S Jr, Lozada-Nur F, Mayer P, Watson JJ
Scala et al., 1997; Kerr, 2000), and it is therefore important that (2001). Oral lichen planus: patient profile, disease progression
every dental care provider be properly educated for this task and treatment responses. J Am Dent Assoc 132:901-909.
(Horowitz et al., 1996, 2000; Downer et al., 1998) to prevent or Crosthwaite N, Teale D, Franklin C, Foster GA, Stringer BM
reduce the delay of a cancer diagnosis (Khoo et al., 1998). (1996). p53 protein expression in malignant, pre-malignant
In countries with few dentists or other oral health care and non-malignant lesions of the lip. J Clin Pathol 49:648-653.
providers, it is most likely difficult for any recall routines for Downer MC, Jullien JA, Speight PM (1998). An interim determi-
nation of health gain from oral cancer and precancer screen-
OLP to be implemented (Warnakulasuriya and Nanayakkara,
ing: 3. Preselecting high risk individuals. Community Dent
1991). Available economic resources should be used to devel- Health 15:72-76.
op models to educate health care professionals and to establish Drangsholt M, Truelove E, Morton T, Epstein J (2001). A man with
nation-wide promotional campaigns to raise public awareness a 30-year history of oral lesions. J Evid Base Dent Pract 1:123-134.
of precancer and oral cancer. Duffey DC, Eversole LR, Abemayor E (1996). Oral lichen planus
In summary, there are sufficient criteria to define what we and its association with squamous cell carcinoma: an update
presently regard as OLP with reasonable certainty. Patients fulfill- on pathogenesis and treatment implications. Laryngoscope
ing the commonly used criteria of OLP appear to have an increased 106:357-362.
risk of developing oral cancer. The observed incidence of oral can- Eisenberg E (2000). Oral lichen planus: a benign lesion. J Oral
cer development is low, and there are no data at this point demon- Maxillofac Surg 58:1278-1285.
strating that intensive follow-up of OLP patients results in reduced Eisenberg E, Krutchkoff DJ (1992). Lichenoid lesions of oral
mucosa. Diagnostic criteria and their importance in the
morbidity and mortality of oral cancer related to OLP.
alleged relationship to oral cancer. Oral Surg Oral Med Oral
Consequently, on a practical and economic basis, a continuous Pathol 73:699-704.
recall of all OLP patients in specialist clinics cannot by justified. It Eisenberg E, Murphy GF, Krutchkoff DJ (1987). Involucrin as a
is important, however, that every dentist and dental auxiliary be diagnostic marker in oral lichenoid lesions. Oral Surg Oral Med
educated to detect early signs of oral cancer to ensure that these Oral Pathol 64:313-319.
lesions are identified when the patients are seen for other purpos- Ellis JR, Gleeson FV (2001). Lung cancer screening. Br J Radiol
es, such as routine examination and treatment. The patient should 74:478-485.
also be instructed to report clinical changes in the condition. Epstein JB, Scully C (1997). Assessing the patient at risk for oral
squamous cell carcinoma. Spec Care Dentist 17:120-128.
Faraci RP, Schour L, Graykowski EA (1975). Squamous cell carci-
REFERENCES noma of the oral cavity—chronic oral ulcerative disease as a
Abramova EJ (1968). [Lichen ruber planus of the oral cavity]. possible etiologic factor. J Surg Oncol 7:21-26.
Dermatol Wochenschr 154:315-323. Fontana RS, Sanderson DR, Taylor WF, Woolner LB, Miller WE,
Allen CM (1998). Is lichen planus really premalignant? [editorial]. Muhm JR, et al. (1984). Early lung cancer detection: results of
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 85:347. the initial (prevalence) radiologic and cytologic screening in
Altman J, Perry H (1961). The variations and course of lichen the Mayo Clinic study. Am Rev Respir Dis 130:561-565.
planus. Arch Dermatol 84:179-191. Fontana RS, Sanderson DR, Woolner LB, Taylor WF, Miller WE,
Alvi A (1996). Oral cancer: how to recognize the danger signs. Muhm JR (1986). Lung cancer screening: the Mayo program. J
Postgrad Med 99:149-152, 155-146. Occup Med 28:746-750.
Andreasen J (1968). Oral lichen planus: 1. A clinical evaluation of Fossion E, De Coster D, Ehlinger P (1994). [Oral cancer: epidemi-
115 cases. Oral Surg Oral Med Oral Pathol 25:31-42. ology and prognosis]. Rev Belge Med Dent 49:9-22.
Axéll T (1976). A prevalence study of oral mucosal lesions in an Fowler CB, Rees TD, Smith BR (1987). Squamous cell carcinoma
adult Swedish population. Odontol Revy 27(Suppl 36):1-103. on the dorsum of the tongue arising in a long-standing lesion
Barnard NA, Scully C, Eveson JW, Cunningham S, Porter SR of erosive lichen planus. J Am Dent Assoc 115:707-710.
(1993). Oral cancer development in patients with oral lichen Fulling HJ (1973). Cancer development in oral lichen planus. A
planus. J Oral Pathol Med 22:421-424. follow-up study of 327 patients. Arch Dermatol 108:667-669.
Bolewska J, Reibel J (1989). T lymphocytes, Langerhans cells and Girod SC, Krueger G, Pape HD (1993). p53 and Ki 67 expression
HLA-DR expression on keratinocytes in oral lesions associat- in preneoplastic and neoplastic lesions of the oral mucosa. Int
ed with amalgam restorations. J Oral Pathol Med 18:525-528. J Oral Maxillofac Surg 22:285-288.
Bolewska J, Hansen HJ, Holmstrup P, Pindborg JJ, Stangerup M Girod SC, Kramer C, Knufermann R, Krueger GR (1994). p53
(1990). Oral mucosal lesions related to silver amalgam restora- expression in the carcinogenesis in the oral mucosa. J Cell
tions. Oral Surg Oral Med Oral Pathol 70:55-58. Biochem 56:444-448.

394 Crit Rev Oral Biol Med 13(5):390-396 (2002)

Downloaded from http://cro.sagepub.com by on June 26, 2010
Girod SC, Cesarz D, Fischer U, Krueger GR (1995). Detection of ments]. J Can Dent Assoc 61:792-796.
p53 and MDM2 protein expression in head and neck carcino- Lo Muzio L, Mignogna MD, Favia G, Procaccini M, Testa NF,
genesis. Anticancer Res 15:1453-1457. Bucci E (1998). The possible association between oral lichen
Häkkinen L, Kainulainen T, Salo T, Grenman R, Larjava H (1999). planus and oral squamous cell carcinoma: a clinical evalua-
Expression of integrin alpha9 subunit and tenascin in oral tion on 14 cases and a review of the literature. Oral Oncol
leukoplakia, lichen planus, and squamous cell carcinoma. Oral 34:239-246.
Dis 5:210-217. MacDonald DG (1975). Premalignant lesions of oral epithelium.
Handlers JP (2001). Diagnosis and management of oral soft-tissue In: Oral mucosa in health and disease. Dolby AE, editor.
lesions: the use of biopsy, toluidine blue staining, and brush London: Blackwell Scientific Publications, pp. 343-344.
biopsy. J CA Dent Assoc 29:602-606. Marder MZ, Deesen KC (1982). Transformation of oral lichen
Harland CC, Phipps AR, Marsden RA, Holden CA (1992). planus to squamous cell carcinoma: a literature review and
Squamous cell carcinoma complicating lichen planus of the report of case. J Am Dent Assoc 105:55-60.
lip. J R Soc Med 85:235-236. Markopoulos AK, Antoniades D, Papanayotou P, Trigonidis G
Holmstrup P (1992). The controversy of a premalignant potential (1997). Malignant potential of oral lichen planus; a follow-up
of oral lichen planus is over. Oral Surg Oral Med Oral Pathol study of 326 patients. Oral Oncol 33:263-269.
73:704-706. Massa MC, Greaney V, Kron T, Armin A (1990). Malignant trans-
Holmstrup P, Pindborg JJ (1979). Erythroplakic lesions in relation formation of oral lichen planus: case report and review of the
to oral lichen planus. Acta Derm Venereol Suppl 59:77-84. literature. Cutis 45:45-47.
Holmstrup P, Thorn JJ, Rindum J, Pindborg JJ (1988). Malignant Mignogna MD, Lo Muzio LL, Lo Russo LL, Fedele S, Ruoppo E,
development of lichen planus-affected oral mucosa. J Oral Bucci E (2001). Clinical guidelines in early detection of oral
Pathol 17:219-225. squamous cell carcinoma arising in oral lichen planus: a 5-year
Horowitz AM, Goodman HS, Yellowitz JA, Nourjah PA (1996). experience. Oral Oncol 37:262-267.
The need for health promotion in oral cancer prevention and Moncarz V, Ulmansky M, Lustmann J (1993). Lichen planus:
early detection. J Public Health Dent 56:319-330. exploring its malignant potential. J Am Dent Assoc 124:102-108.
Horowitz AM, Drury TF, Goodman HS, Yellowitz JA (2000). Oral Murti PR, Daftary DK, Bhonsle RB, Gupta PC, Mehta FS,
pharyngeal cancer prevention and early detection. Dentists’ Pindborg JJ (1986). Malignant potential of oral lichen planus:
opinions and practices [see comments]. J Am Dent Assoc observations in 722 patients from India. J Oral Pathol 15:71-77.
131:453-462. Pogrel MA, Weldon LL (1983). Carcinoma arising in erosive lichen
Hugoson A, Koch G, Bergendal T, Hallonsten AL, Slotte C, planus in the midline of the dorsum of the tongue. Oral Surg
Thorstensson B, et al. (1995). Oral health of individuals aged 3- Oral Med Oral Pathol 55:62-66.
80 years in Jönköping, Sweden in 1973, 1983, and 1993. I. Porter SR, Lodi G, Chandler K, Kumar N (1997). Development of
Review of findings on dental care habits and knowledge of squamous cell carcinoma in hepatitis C virus-associated lichen
oral health. Swed Dent J 19:225-241. planus. Oral Oncol 33:58-59.
Janner M, Muissus E, Rohde B (1967). [Lichen planus as a possible Rajentheran R, McLean NR, Kelly CG, Reed MF, Nolan A (1999).
precancerous condition]. Dermatol Wochenschr 153:513-518. Malignant transformation of oral lichen planus. Eur J Surg
Kabani S, Dhingra JK (1997). Early detection is critical for oral can- Oncol 25:520-523
cer patients. J MA Dent Soc 46:41-43, 46-48. Salem G (1989). Oral lichen planus among 4277 patients from
Kainulainen T, Autio-Harmainen H, Oikarinen A, Salo S, Gizan, Saudi Arabia. Community Dent Oral Epidemiol
Tryggvason K, Salo T (1997). Altered distribution and syn- 17:322-324.
thesis of laminin-5 (kalinin) in oral lichen planus, epithelial Scala M, Moresco L, Comandini D, Monteghirfo S, Tomei D (1997).
dysplasias and squamous cell carcinomas. Br J Dermatol [The role of the general practitioner and dentist in the early
136:331-336. diagnosis of preneoplastic and neoplastic lesions of the oral
Katz RW, Brahim JS, Travis WD (1990). Oral squamous cell carci- cavity]. Minerva Stomatol 46:133-137.
noma arising in a patient with long-standing lichen planus. A Scully C, Ward-Booth RP (1995). Detection and treatment of early
case report. Oral Surg Oral Med Oral Pathol 70:282-285. cancers of the oral cavity. Crit Rev Oncol Hematol 21:63-75.
Kerr AR (2000). Lifesaving oral cancer screening. NY State Dent J Scully C, Beyli M, Ferreiro MC, Ficarra G, Gill Y, Griffiths M, et al.
66:26-30. (1998). Update on oral lichen planus: etiopathogenesis and
Khoo SP, Shanmuhasuntharam P, Mahadzir WM, Tay KK, Latif A, management. Crit Rev Oral Biol Med 9:86-122.
Nair S (1998). Factors involved in the diagnosis of oral squa- Shklar G (1972). Lichen planus as an oral ulcerative disease. Oral
mous cell carcinoma in Malaysia. Asia Pac J Public Health Surg Oral Med Oral Pathol 33:376-388.
10:49-51. Shugars DC, Patton LL (1997). Detecting, diagnosing, and pre-
Kovesi G, Bánóczy J (1973). Follow-up studies in oral lichen venting oral cancer. Nurse Pract 22:105, 109-110, 113-105 passim.
planus. Int J Oral Surg 2:13-19. Sigurgeirsson B, Lindelof B (1991). Lichen planus and malignancy.
Krutchkoff DJ, Eisenberg E (1985). Lichenoid dysplasia: a dis- An epidemiologic study of 2071 patients and a review of the
tinct histopathologic entity. Oral Surg Oral Med Oral Pathol literature. Arch Dermatol 127:1684-1688.
60:308-315. Silverman S Jr (1992). Precancerous lesions and oral cancer in the
Krutchkoff DJ, Eisenberg E (1986). Lichen planus: significant pre- elderly. Clin Geriatr Med 8:529-541.
malignant potential? [letter]. Arch Dermatol 122:504-505. Silverman S Jr (1993). A look at oral cancer lesions: prevention,
Krutchkoff DJ, Cutler L, Laskowski S (1978). Oral lichen planus: early detection keys to survival. Dent Teamwork 6:31-32.
the evidence regarding potential malignant transformation. J Silverman S (1994). Oral cancer. Semin Dermatol 13:132-137.
Oral Pathol 7:1-7. Silverman S Jr (2000). Oral lichen planus: a potentially premalig-
Leong IT, Main JH, Birt BD (1995). Cancer of the tongue [see com- nant lesion. J Oral Maxillofac Surg 58:1286-1288.

13(5):390-396 (2002) Crit Rev Oral Biol Med 395

Downloaded from http://cro.sagepub.com by on June 26, 2010
Silverman S Jr, Bahl S (1997). Oral lichen planus update: clinical Bezemer PD, van der Waal I (1999b). A review of the recent
characteristics, treatment responses, and malignant transfor- literature regarding malignant transformation of oral lichen
mation. Am J Dent 10:259-263. planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod
Silverman SJ, Gorsky M, Lozada-Nur F (1985). A prospective fol- 88:307-310.
low-up study of 570 patients with oral lichen planus: persis- Vas’kovskaia GP, Abramova EI (1981). [Development of cancer in
tence, remission and malignant association. Oral Surg Oral lichen planus foci of the oral and vermilion border mucosa].
Med Oral Pathol 60:30-34. Stomatologiia (Mosk) 60:46-48.
Silverman S Jr, Gorsky M, Lozada-Nur F, Giannotti K (1991). A Voute AB, de Jong WF, Schulten EA, Snow GB, van der Waal I
prospective study of findings and management in 214 (1992). Possible premalignant character of oral lichen planus.
patients with oral lichen planus. Oral Surg Oral Med Oral The Amsterdam experience. J Oral Pathol Med 21:326-329.
Pathol 72:665-670. Warin RP (1960). Epithelioma following lichen planus of the
Sudbo J, Kildal W, Risberg B, Koppang HS, Danielsen HE, Reith A mouth. Br J Dermatol 72:288-291.
(2001). DNA content as a prognostic marker in patients with Warnakulasuriya KA, Nanayakkara BG (1991). Reproducibility of
oral leukoplakia. N Engl J Med 344:1270-1278. an oral cancer and precancer detection program using a pri-
Thorn JJ, Holmstrup P, Rindum J, Pindborg JJ (1988). Course of mary health care model in Sri Lanka. Cancer Detect Prev
various clinical forms of oral lichen planus. A prospective fol- 15:331-334.
low-up study of 611 patients. J Oral Pathol 17:213-218. Zhang L, Michelsen C, Cheng X, Zeng T, Priddy R, Rosin MP
van der Meij EH, Reibel J, Slootweg PJ, van der Wal JE, de Jong (1997). Molecular analysis of oral lichen planus. A premalig-
WF, van der Waal I (1999a). Interobserver and intraobserver nant lesion? Am J Pathol 151:323-327.
variability in the histologic assessment of oral lichen planus. J Zhang L, Cheng X, Li Y, Poh C, Zeng T, Priddy R, et al. (2000).
Oral Pathol Med 28:274-277. High frequency of allelic loss in dysplastic lichenoid lesions.
van der Meij EH, Schepman KP, Smeele LE, van der Wal JE, Lab Investig 80:233-237.

396 Crit Rev Oral Biol Med 13(5):390-396 (2002)

Downloaded from http://cro.sagepub.com by on June 26, 2010