Bouquot et al

Oral Precancer and Early Cancer Detection in the
Dental Office – Review of New Technologies

Jerry E. Bouquot, DDS, MSD1 • Patricia Suarez, DDS, MS2
Nadarajah Vigneswaran, BDS, DMD3

Abstract

Background: New technologies have provided Methods: Extensive literature review, personal
an exciting new array of clinical diagnostic tools experience and discussion with other profes-
for localizing or emphasizing abnormal mucosa sionals with clinical experience with these tech-
in the dental office, especially leukoplakia and nologies were used in order to provide a critical
dysplasia. Some of these technologies claim to summary and evaluation of available technologies.
identify atypical cells prior to biopsy, even before
there are clinically visible mucosal changes, Conclusions: Most technologies are ben-
hence, can allow a more confident assessment eficial but must be used with intelligence and
of risk and localization of the most “suspicious” must be considered adjunctive tests rather than
area to biopsy. In essence, molecular-level detec- stand-alone diagnostic tools. Loss of autofluo-
tion of dysplastic oral mucosal change appears rescence seems to hold the most promise for
to be moving into the practitioner’s office. identifying mucosal dysplasia, but several non-
dysplastic lesions may also be nonfluorescent
and occasional false positive results do occur.

KEY WORDS: Oral cancer, oral diagnosis, leukoplakia, erythroplakia, cytology

1. Professor and Chair, Department of Diagnostic Sciences University of Texas Dental Branch at Houston, Houston, Texas
2. Assistant Professor, Department of Diagnostic Sciences University of Texas Dental Branch at Houston, Houston, Texas
3. Professor, Department of Diagnostic Sciences University of Texas Dental Branch at Houston, Houston, Texas

The Journal of Implant & Advanced Clinical Dentistry • 47

as well as with increased and alveolar keratosis. and the various oral precancerous lesions.Bouquot et al INTRODUCTION The idea of precancer has been a slowly changing and often confusing concept.8 This defi- in approximately 3% of U.1 With today’s definition.3 tional workshops to redefine the term “precancer” He mentioned that he saw his first cancer trans. ation except.5 We now know that leukoplakia represents disease” and is not associated with an obvious more than 80% of all oral precancers.8 This panel tried to completely elimi- mucosa of the hard palate is. in inveterate pipe smokers carried an increased risk of eventual cancer transformation. not the carcino. one of the nate the term “leukoplakia” because of its progres- least likely sites for oral cancer development. we no most recent workshop. have a rich and fascinating literature extend- ing as far back as the 1870s. years of age.7 Because of once included in the diagnosis of leukoplakia. preferring rather to think of it as a response “precancer” and the use of the presumably more to the heat of tobacco smoke.2. The formation in this disease in 1851.2. relatively thin white keratotic patch. 3 • April 2010 . (Figure 1). beginning with the 1805 suggestion by an European panel of phy- sicians that there are benign diseases which will always develop into invasive malignancy if followed long enough. as a “white patch or plaque that cannot be char- ian dermatologist. when Sir James Paget. Ironically. first coined the acterized clinically or pathologically as any other term. Schwimmer. No. 2. a risk which has been plaques of the mouth. illuminating term “potentially malignant lesion” for gens. the World Health does not imply a specific microscopic tissue alter- Organization has periodically convened interna. no better diagnostic term could be found. is found etiologic agent except tobacco use. leukoplakia today is defined discussed since before 1876.2 sively changing definition over time. a precan- cer is considered to only hold an increased risk of cancer transformation. leukoplakia the day. has demonstrated a far greater risk of Once applied to any and all white mucosal malignant transformation. all diseases which were daily usage of smoked tobacco. nicotine palatinus with increasing age.S. proposed that “leukokeratosis” or “smoker’s Figure 1: Leukoplakia of the ventral tongue is seen as a patch” of the hard palate (nicotine palatinus). term is now used in a strictly clinical sense and ing oral precancer concepts.6.4 The heavily keratinized. held in London in 2005. actually recommended the elimination of the term cer. adults older than 35 nition excludes lichen planus.e. longer consider nicotine palatinus to be a precan. the excess surface keratin 48 • Vol. frictional keratosis. “protected” oral lesions. of course.2 Oral precancers. in fact. The the continuing challenge and confusion surround. one of England’s most renowned surgeons. or well demarcated.3. At the end of Another white keratotic lesion. and shows an increasing prevalence smokeless tobacco keratosis. the tongue. i. in partic- ular. when the Hungar.3.

although few have been followed for an entire lifetime).7. the clinical entity called leukoplakia is generally thought to carry a malignant transfor- mation rate of approximately 4% (presumably a lifetime risk. How often are dysplastic cells found in leuko- formation. For example.12 are known to increase the risk of cancer trans.2. only 5%-25% of plakia and its less common but more serious red leukoplakias will actually show dysplastic epithe- counterpart. although almost 90% of The Journal of Implant & Advanced Clinical Dentistry • 49 .9. oral dysplasia follow-up investigations have con- fined themselves to severe dysplasias or carci- which is responsible for the white color change. erythroplakia (Figure 2).7. the most significant prognostic indicators. surface). often combining the two. a well demarcated red patch with areas of pebbled or showing atypical keratinocytes and irregular ret tips in the granular surface change (some lesions have a smooth lower portion of the epithelium. noma in situ.9 The transformation rate for lesions with epithelial dysplasia is much higher. since both While certain clinical alterations in leukoplakia appear to have similar biological behaviors.7-11 Figure 4: Speckled leukoplakia (erythroleukoplakia) of the Less dysplastic epithelium is much less worrisome oral floor shows multiple pink areas surrounded by a white in this regard and so the most significant of the keratotic plaque. Bouquot et al Figure 2: Erythroplakia of the ventral tongue is seen as Figure 3: Histopathology of moderately severe dysplasia. it is the microscopic features of leuko. approximating 4-11% for moderately severe dys- plasia and 20-35% for severe dysplasia (Figure 3). with malignant transformation usually occur- ring within 3 years of the dysplasia diagnosis. which are lial cells when biopsied. plakia or erythroplakia? Overall.

with oral leukoplakia ? a. reverse smoking: smoking with the lit end of the cigarette in one’s mouth b. 2. designated by the 2005 WHO Workshop on Oral Premalignancies as not a precancer8.Bouquot et al Table 1: Precancerous lesions of the oral. Farthing. clinical terms only (modified from Bouquot. 2005.10 50 • Vol. as suggested in the literature. with dorsal leukoplakia *** Smooth.7) Disease Name Malignant Transformation Potential Proliferative verrucous leukoplakia (PVC) ****** Nicotine palatinus in reverse smokersa ***** Erythroplakia ***** Oral submucous fibrosis. with oral leukoplakia ? Epidermolysis bullosa. with oral ulcers/keratosis ? Dyskeratosis congenita. with leukoplakia ***** Erythroleukoplakia **** Granular leukoplakia **** Laryngeal keratosis *** Actinic cheilosis *** Syphilitic glossitis. Speight. thick leukoplakia ** Smokeless tobacco keratosis ** Plummer-Vinson disease (sideropenic dysphagia. 3 • April 2010 . pharyngeal and laryngeal mucosa. erosive formsb * Smooth. with oral leukoplakia ? Clarke-Howel-Evans syndrome. smooth tongue) * Lichen planus. No. thin leukoplakia +/- Lupus erythematosus.

significantly. of course. plastic cells in oral leukoplakias. hopefully. In plastic oral mucosal change appears to be mov- fact. a time-honored. result in poor follow-up of the lesion.17 This review Certain clinical features. in turn. each identifies 1960s because it seemed unable to find dys- potential biopsy sites most likely to contain dys. where the cells are removed and plated predictive in almost half of oral precancers and on a microscopic slide. Bouquot et al erythroplakias will do so. we can We certainly need help with this dilemma. technologies. The Journal of Implant & Advanced Clinical Dentistry • 51 . arise.13. Dysplastic or immature epithelial cells may.8. The latter point is extremely impor. come new respon- mine which leukoplakias are the high risk lesions? sibilities and new problems. since a negative a thicker keratin layer than their cervical coun- biopsy will give a false sense of security which terparts. general dentist with help that can be used in an The brush biopsy or Oral CDx test has over- office setting.12 Therefore. more recently. process is the same as a routine pap smear. This is undoubt- plastic cells. From that point on. edly due to the fact that oral white patches have tant for a large leukoplakia.7 Today pap smears are used effectively for In the hands of an experienced clinician they have oral red lesions and oral ulcers to identify infec- served remarkably well. For. a disease in which dysplas- to make ideal decisions about these lesions. effective tool ative mucosal breakdown are all significant in this for finding dysplastic cells of the uterine cer- regard (Figure 4). and should not be expected to be clinical features have been the only guide we found by scraping a thick surface layer of kera- have had for risk assessment of oral precancers. tic epithelial cells are typically near the surface. will attempt to describe the pros and cons of rough or granular surface changes. In essence. such as large size. With these new no evidence of atypia.14 Each of these suggests vix lost popularity among dentists during the increased risk and. The Pap smear. When dysplastic cells do occur in come this fatal shortcoming by screwing a bris- an oral leukoplakia or erythroplakia. Unfortunately.2. red or pink the recent and latest of these technologies. This point is especially sig. The Brush Biopsy plakia). these tech. and ulcer. A als with a precancer or cancer of the mouth.18 This relatively painless proce- assessment of risk and identify a more “suspi. the that the entire oral mucosa is at risk in individu.16 cytotechnologist.7. tin. pathologist or. from the bottom of the squamous For several decades the above mentioned epithelium. multiple leukoplakic lesions. the great majority of leukoplakic lesions show ing into the practitioner’s office. as always. patches incorporated within the white patch of a leukoplakia (speckled leukoplakia. to allow a more confident lium (Figure 5A). How then can we deter. dure captures the deeper epithelial cells on the cious” area to biopsy. tunately. logically consider all erythroplakias to be high risk. new technologies are providing the They are seldom used for white keratotic lesions.15. tle-covered wire (the “brush”) through the thick nologies claim to help identify them prior to surface keratin to the basal layer of the epithe- biopsy and. bristles and the entire brush is sent to a pathol- nificant when one knows that the biopsy is not ogy lab. erythroleuko. and atypical cells lack the level of experience or expertise required in erythroplakia. molecular-level detection of dys- but the same cannot be said for leukoplakias. most of us tions. especially candidiasis.

ogy replacing conventional smears. 52 • Vol. 2. owing to pares the size of each individual cell with the better cell recovery and morphologic preserva- size of its nucleus.19 One method uses a filtration process and Recently. liquid-based cytology (LBC) has a computer-assisted thin layer deposition of cells become a principle methodology in cytopathol. (Thinprep® CYTYC Corp. Large. Results are usu. Newark. MA). 3 • April 2010 . New Jersey). Boxborough. as are abnormal has approved two LBC methods for gynecologic nuclear shapes (pleomorphism). Figure 6a: Thin leukoplakia of oral floor has a slight Figure 6b: Toluidine blue staining identifies areas of erythematous background. dark nuclei are found tion. No.Bouquot et al Figure 5a: The Oral CDx brush biopsy is twisted into the Figure 5b: One of the LBC brushes in use.. and non-gynecologic cytologic sample process- ally reported out as one of three levels of risk. mucosa. New Jersey Medical and Dental University. Hille Ephros. ing. a computer-associated optical scanner com. potential biopsy (dysplasia) (photo: Dr. The Food and Drug Administration (FDA) in dysplastic or immature cells.

Unfortu- adjunctive technologies for oral dysplasia.23-25 It frequently needs to cers and can properly identify the most “severe” be repeated because the false positive tests are area to brush. Gynecologists have long been aware of the abil- ity of acetic acid to enhance regions of thickened Toluidine Blue – in Vivo Staining of DNA surface keratin of the uterine cervix. large nuclei.6b). as with all sia prior to definitive oral cancer surgery. cially effective with erythroplakia and carcinoma is not a good screening procedure and no stud. This the ubiquitous inflammatory cells that may inter. to find “outlier” areas of dyspla- The brush biopsy and LBC. more visible to the naked matic dye long used in histology laboratories to eye.18. brush biopsy is not a true diagnostic tool and cannot.20. it makes the keratin more Toluidine blue (tolonium chloride) is a metachro. requires that the clinician be relatively knowl. however. and there are high proportions of false positives edgeable about the clinical features of precan. It also implies that the clinician is often trauma. Even derline ones that should be “brush biopsied. Both used. the toluidine blue test is a good tool in an experienced. It is also not possible with conventional cytologic smears. likewise. in situ. since it stains DNA very have been missed could be detected after a min- The Journal of Implant & Advanced Clinical Dentistry • 53 . Bouquot et al while the other method involves a sedimentation well. and has been added to another also provides additional samples for immunohis. for of these methods produce an evenly distributed oral precancer detection by staining.17 It appears to not only increase the sensitivity and has recently been FDA cleared for use within the specificity of cytologic diagnosis but. A thin leukoplakia which might otherwise stain nuclear material. Burlington. requiring be used with intelligence and its routine use an acetic acid (vinegar) rinse before and after. white and. test is premised on the fact that mucosal cells fere with cytologic examination. with very few false positive or negative experience. significantly. In the oral in the Dental Office environment.23. used in the U. in the den- thin layer of epithelial cells devoid of blood and tal office. the help to localize areas to biopsy or to brush biopsy. LBC had been with extra DNA. knowledgeable can be a good adjunctive test in the hands of an hand.21 LBC methodology washed off with acetic acid (Figures 6a. and false negatives.or inflammation-related. i. therefore.e. must nately. United States. even after the bulk of the stain has been oral mucosa (Figure 5B). attract and retain adopted to analyze the brush biopsy samples of the stain.24 It should not be considered a stand- ies have correlated normal mucosa with brush alone test and will not give a diagnosis. and is espe- results when used appropriately. knowledgeable clinician.” It with its limitations. but it can biopsy results. capable of distinguishing between lesions which the dysplastic cells lying deeply in a thick keratotic should be biopsied immediately and those bor. living cells.22 However.17 Perhaps more significantly. primarily outside the United States. provide a definitive diagnosis The ViziLite – Highlighting the Keratin – an incisional biopsy is always needed for that. NC). Moreover. lesion will likely not be stained adequately.S. therefore. the ViziLite(R) system to improve the tochemical and other molecular studies which are effectiveness of that test (see following). the nuclei of immature. this dye test is awkward to use. For several decades now it has also been process (TRiPath Imaging. technology.

No. 2. should more readily identify the more noticeable.29 The light manufacturer claims that “light from ViziLite(R) is is derived from either chemical tubes (chemilumi. although the addition of toluidine blue of seems to have a high proportion of false positive the ViziLite Plus(R) system is capable of identi- and false negative tests. toluidine blue plastic tissue. mucosa which is “normal” according to the test. should have no effect on our ability to see dys- As with other adjunctive diagnostic technolo. absorbed by normal tissue and reflected by dys- nescence) or a laser and. It keratin. And the relatively limited so reflected light will identify such cells only if they clinical research related to the ViziLite(R) has not are associated with surface hyperkeratosis. intensify innocu- system takes advantage of this and adds bright ous keratotic lesions such as smokeless tobacco blue light to even further enhance keratin detec. hence.28. but underlying epithelial atypia dysplastic cells in the affected epithelium.29 As an adjunctive 54 • Vol. for example. despite the fact that there are never hyperkeratosis on the left.g. relative to identification fying dysplastic or immature cells when they are of dysplastic cells rather than hyperkeratosis.26-28 This technology uses reflected light solely ally. is seen on both right and left sides. It is best performed in most superficial cell layers. however. With this caveat. ute of contact with acetic acid. plasia unless associated with excess surface gies. the ViziLite(R) exam has disadvantages. reflected light identification of superficial nuclear abnormalities. it does well. The ViziLite(R) It would constantly. keratosis and leukoedema (Figure 8). with a very high ability to enhance Is this a worthwhile screening test? The identification of keratotic patches. a completely dark room. e.”30 How- has been added to the kit (ViziLite Plus(R)) for ever. Dysplasia. looked at the microscopic appearance of oral leukoplakia (Figure 7). recently. which will appear white. 3 • April 2010 . of course. which is often difficult in begins in the lowest layers of the epithelium and today’s dental offices.29 close enough to the surface.Bouquot et al Figure 7: The ViziLite is good at emphasizing keratotic Figure 8: The ViziLite will make this leukoedema much surface change.17.26. Addition- tion. this seems counter-intuitive. it requires a swish with acetic acid before and and so can only give us information from the after the light examination.

autofluorescence in multiple areas (arrows). Whether or not it can detect dent on the molecular composition of the same dysplastic cells without toluidine blue staining. been adequately proven and. test. mira.28 adenine dinucleotide). How- orescence. especially when activated (excited) by ever. certainly not capable of our cells contain molecules capable of self-flu. this system is valuable in that it increases specific light waves. to have culminated in a Nobel Prize in Chemistry. of being seen under normal conditions. to a certain degree. these fluorescing and in the absence of surface keratin. BC. Houston. with dysplasia (marked “D”) seen microscopically in three sites. we all glow. certainly. Each living tissues is very slight. certainly. and flavins (FAD. flavin tle or nothing to the routine visual examination. LLC. elastin. Canada) introduced three medical research have been significant enough years ago. together with the subsequent biological and tal.32. if violet or blue light is used in a darkened The Journal of Implant & Advanced Clinical Dentistry • 55 .35 In humans. Inc. and the new Identafi(R) 3000 Ultra (Tri. NADH (nicotinamide those who considered the technology to add lit. Texas). porphyrins. adenine dinucleotide). find hyperkeratotic differences in the index of refraction of different patches that may have been missed with routine tissue components. there are collagen cross-links. components. White Rock. Bouquot et al Figure 9a: Actinic cheilosis in a 37 year old woman has an Figure 9b: The VELscope shows considerable loss of innocuous appearance. the VELScope(R) (LED Den. has not products are numerous: tryptophan. while absorption is depen- visual inspection. teins. Doesn’t Glow The discovery and harnessing of fluorescent pro- Two optical devices. and it should. take advantage of the The amount of fluorescence given off from fact that.34 This fluorescent signal- ing has been used to assess the metabolic state Oral Autofluorescence – When the Mucosa of tissues and to identify primitive/dysplastic cells.31-35 Excitation and emission awareness of the oral cancer and precancer of fluorescence depends on how light is scattered detection dilemma for both the clinician and the and absorbed in tissue: scattering is caused by patient.

which is mounted in the hand-held light emitting “gun. Figure 11a: The VELscope autofluorescence device. the user looks through special filtering 56 • Vol. stimulates a blue/violet fluorescence. shape and weight of a dental hand- greatest fluorescence in oral mucosa range piece.Bouquot et al Figure 10a: The Identafi(R) 3000 Ultra with filtering goggles Figure 10b: Using the green light during an oral to be worn by the clinician. No. the autofluorescence is easily seen (Fig. Figure 11b: In clinical use. The light sues. i. room and the clinician peers through an eye. The wavelengths which excite the the size. 2. shines from a battery-powered device roughly ures 9a. the operator looks through the eyepiece. piece or pair of glasses which filter out virtually The Identafi(R)3000 Ultra shines a violet all reflected light and only allows transmission of light of approximately 405 nm. which especially light of the wavelength(s) of the fluorescing tis.e. from 400 to 460 nm. examination. 3 • April 2010 . violet and blue light.” while the patient wears protective eye gear.9b).

vides two other types of light: a white light suit. Figure 13a: Poorly visualized whitish change of the Figure 13b: Well demarcated loss of autofluorescence anterior oral floor was diagnosed as severe dysplasia by in area of dysplasia (photo: Dr. rescence. somewhat autofluorescence (using Identafi(R) 3000 Ultra violet light) pebbled patch. 10b). M. and peak intensity at approximately 436 nm. (photo: Dr. Catherine Poh. Canada). biopsy. Anne Gillenwater. The device shines light out of a hand- erated light is less intense or bright than that of held “gun” that is tethered to a light source the VELscope(R) but this does not seem to influ. Bouquot et al Figure 12a: Squamous cell carcinoma of the left ventral Figure 12b: Entire lesions show a considerable loss of and lateral tongue presents as an innocuous. Houston. Texas). Anderson Cancer Center. This device also pro. glasses (Figures 10a. The VELScope(R) uses a blue light with able for a conventional visual examination. ence the amount of tissue fluorescence given off. The gen.D. this a green-amber light that highlights keratinized wavelength especially stimulates a green fluo- mucosa and submucosal blood vessels. British Columbia. Vancouver. University of British Columbia. which typically remains on a cart or counter The Journal of Implant & Advanced Clinical Dentistry • 57 .

with 4 equally complete loss of fluorescence (very dark region of mucosa).Bouquot et al Table 2: Autofluorescence outcomes with various oral lesions. No. using a 0-4 point scale. subepithelial congestion) * 2-3 Squamous papilloma 1-3 Inflammatory congestion 1-3 Mild cheek bite (with or without hyperkeratosis) 1-2 Mild tongue thrust habit (lateral margins) 1-2 Leukoplakia without epithelial dysplasia 0-1 * fibromas without such surface irritation are brightly fluorescent 58 • Vol. These outcomes are based on the anecdotal experience of numerous clinicians with extensive experience using autofluorescing devices. 2. Amount of Autofluorescence Loss Disease/Lesion (Maximum = 4) Leukoplakia with epithelial dysplasia 3-4 Dysplasia without white or red color 3-4 Melanosis 3-4 Amalgam tattoo 3-4 Tonsil tag (lymphoid aggregate) 3-4 Focal epithelial hyperplasia (FEH) 3-4 Hemangioma/venous lake 3-4 Geographic tongue (depapillated area) 2-4 Lichen planus (erosive type only) 2-4 Irritation fibroma (with continued surface Irritation. 3 • April 2010 .

epithelial influence on the subepithelial stroma 14b) and melanin deposition produce the impres.13). as well as the subepithelial colla.12. by the wavelengths use by the oral devices fluorescence between normal oral mucosa and in use today.35. These links. lagen fibers by less fluorescent leukocytes. tionally. The rea- with visible light. If there are numer. The Journal of Implant & Advanced Clinical Dentistry • 59 . And finally. for reasons to the deepest part of the epithelium and so eas. Relative to the dark patches from ally blackish-green or blackish-blue) through the melanin pigmentation. prove to be a bit of a disadvantage in certain set. very well because they are comprised almost tings. This deep penetration can. can be dark when viewed with the VELScope(R) or as much as 12x (Figures 12a. since several nondysplastic tissue changes completely of mature collagen with many cross are also positive with this test (Table 2). however.34. vascularity. such aggregates are typically dysplastic epithelium. and biop. such as candida.37 low or yellow/orange (Figure 17a. typical. Identafi(R)3000 Ultra (Figures 15a. gen almost entirely and leukocytes may lack ing to the “black spot” seen through the filter.35 the autofluorescence molecules influenced Research has shown that the difference in self. The irritation fibroma with secondary ily reaches dysplastic cells in the lower regions of surface irritation and increased subepithelial the epithelium. while black mucosa is highly likely organisms. fluorescence (Figures 16a. 17b). The much less NADH and FAD activity than a nor. data also suggests that the cross-links Aggregates of benign lymphoid tissue. less irritated fibromas fluoresce very. a mimicked loss An immature or dysplastic epithelial cell has of fluorescence (black spot) might result. fied with routine visual or white light examination. 11b). may fluoresce yel- to contain such cells (Figures 13a. 18b). even though more gen fibers. e. this can easily be identi- eyepiece or glasses (Figures 9. 16b). Bac- sies of border regions between green and black teria using different fluorescent cytosol mole- mucosa have shown that the green/blue fluo. Fungal micro- plastic cells. suggests that the erythematous background of tives” but they do require a basic understanding erosive (atrophic) lichen planus typically lacks of common oral lesions and a closer evaluation self-fluorescence (Figures 18a. 13b). contribut. 15b). cules will give off a red. in carcinoma. pink or orange or yellow rescent mucosa is very unlikely to contain dys. or the replacement of dense subepithelial col- sion of loss of fluorescence. lack colla- tic cells also lose fluorescent activity. unknown. the excellent light. For example. our own personal experience additional positive lesions are not true “false posi.g. ous dilated superficial blood vessels immediately and the user looks through a filtered eyepiece beneath the epithelium. thereby appearing black (actu. in subepithelial collagen fibers beneath dysplas. 12b). vascularity may appear dark. son for this is unknown but may have to do with absorbing qualities of hemoglobin (Figures 14a. as can easily occur in that disallows reflective and ambient light. Identafi(R) 3000 attempts to address this issue mal cell and so mucosal areas with such cells by providing a green-amber light which highlights will not fluoresce.35 Addi. such as tonsils or oral tonsil tags. Lesions The beauty of the self-fluorescence test is that of focal epithelial hyperplasia also typically show the light used to excite the oral cells penetrates a moderate loss of fluorescence. Bouquot et al top plugged to the wall (Figures 11a. mild trauma or inflammation.

of the Identafi(R). length and other factors. 2. Houston. 3 • April 2010 . but the greatest hurdle Our experience suggests that these numbers 60 • Vol. Each ana. esophageal examination.Bouquot et al Figure 14a: Buccal mucosa with two small telangiectasias. This makes evaluation very much colonoscopy and skin evaluation. Figure 14b: Vascular lesions show dark areas mimicking loss of fluorescence (using VELscope) (photos: Dr. environment. Robert Anderson. Autofluorescence technology has been to overcome for the routine oral use of this tech- extensively used in endoscopic instruments nology appears to be the need for a dimmed for bronchoscopy. Texas). Figure 15a: Lymphoid aggregate (tonsil tag) of oral floor Figure 15b: Lesion appears very dark with the violet light viewed with amber/green light of the Identafi(R). more efficient and without it there is bound tomic site requires slight variations in wave to be a larger number of true false negatives. No.

Figure 17a: Pseudomembranous candidiasis of left buccal Figure 17b: Yellow autofluorescence with the blue light of mucosa. Houston. Anne Gillenwater. Figure 16b: The leukoplakia shows minimal loss of fluorescence.000 to $7. the Identafi(R) (photos: Dr. Texas). A second nothing and Huff36 feeling that it picked up dys- The Journal of Implant & Advanced Clinical Dentistry • 61 . M. Texas). Houston. lingual bacteria fluoresce pink using the blue light of the Identafi(R) (photos: Dr. Anderson Cancer Center. Bouquot et al Figure 16a: Leukoplakia of the right dorsal tongue. are quite low when the devices are properly concern is that the equipment can be relatively used as part of an overall clinical examination. use of autofluorescence have come to opposite tive tests only. of course.D. again brings to mind the only two published papers dealing with routine premise mentioned previously: these are adjunc. Anne Gillenwater. ranging from $3. with Huber35 feeling that it adds nician to use his or her intelligence. conclusions. expensive. and all such tests require the cli. M.D. Anderson Cancer Center. The This.000.

Bouquot et al Figure 18a: Erosive. No. in much more valuable. plastic lesions missed by routine examination.edu proteomics or genomics. bullous lichen planus of the left Figure 18b: Severe loss of fluorescence of erythematous buccal mucosa. this degree of opposing conclusions is research will undoubtedly improve our ability seen in all of the technologies discussed here. it is refresh- our experience this technology has identified ing to be practicing dentistry during a time of dysplastic.Bouquot@uth. Until then. even microinvasive lesions that were such exciting emerging technologies attempt- completely “normal” looking with visible light. brush biopsy or LBC. at the earliest possible stage. it is heartening to know Phone: 713-500-4420 (cell: 281-745-2330) that relatively acceptable in-office devices are Fax: 713-500-4416 already available and can be used as adjunctive 62 • Vol. 3 • April 2010 . Bouquot technologies over another. background using the violet light of the Identafi(R). Refinements and continued be fair. Houston.D. ● CONCLUSIONS Correspondence: Our intention is not to recommend one of these Dr. All devices University of Texas Dental Branch at Houston have limitations and the published research is 6516 M. dys- but our own opinion is that it is a good idea to plastic changes in our patients. Texas 70030 such as the use of molecular markers in salivary Jerry. Room 3. serious of our oral diagnostic dilemmas. but until other methods are developed. Anderson Blvd sparse. Jerry E.094b either a biopsy. but the future looks most bright for the optical autofluorescence Department of Diagnostic Sci- technology (pardon our pun). 2. to detect. ing to address one of the most frustrating and even to the suspicious eye of an oral pathologist.tmc. combined with ences. Certainly. To diagnostic tools. and new tech- use autofluorescence on an annual basis as a nologies may emerge quickly which will prove screening tool in the dental office.

and FAD redox states. Baillie. Lane PM. Rossie KM. Karrison T. Afify AM. Mayevsky A. 2000. Neville B. PNAS 2007. Assessment of the VEL- sification systems: predictive value. The nology: results from a cohort of normal oral El-Naggar AK. Oral Surg Turner A. Gillenwater AM. Richards-Kortum ment. E.616 white 20. phia: W. from animal models to human studies. Dabelsteen E. 11:024-26. Chen C-H. 37. 2:423-431. Smeets R. Simple device for the direct visualization of The authors wish to thank Dr.vizilite. Texas) for allowing K. The Journal of Implant & Advanced Clinical Dentistry • 63 . scope as an adjunctive examination tool. 7. Oral premalignant lesions: is biopsy reli. Pierre M. for technical 14. Chen Y-K. Redden Weber C. www. Utility of toluidine blue staining and brush J Oral Pathol Med 2007. J Biomed Optics 2006. cer. Oral and maxillofacial pathology. fluorescence lifetimes. Paget J. lichen Diagn Cytopathol 2001. 24. tion in vivo evaluated by NADH fluorescence: J Am Dent Assoc 2002. 29:948-958. Saunders. 44:10–22. 21. in press. lands DES report (England). Critical evaluation of diag- J Oral Pathol Med 2008. 30. Sirois DA. Campo-Trapero J. conditions: an overview of the literature. Schleimhautplauques der Mund- Al-Khafaji B: Comparison of ThinPrep and hohle (Leukoplakia buccalis). Mitochondrial func- U. Oral Oncol 2006. able? J Oral Path Med 2007. Reibel J. 14:47-52. Leukoplakia. May. Improving detection of precancer. Vedtofte P. in patients with head and neck cancer. Marsico A. Autofluorescence imaging and spec- Investigating the Nature and Cure of Cancer. 25(3):177-184. 37:63-69. 17:59-63. Eickhoff J. 2: 382-389. Speight PM. Texas. 7:59-68. Pavlova I. Sroussi Tex Dent J 2009. The authors would also like to thank Dr. from Trimira LLC. properties. Trullenque-Eriksson A. Kalmar JR. Thomson PJ. Oral epithelial dysplasia clas. R. plakia--rationale for diagnosis and prog. Patton LL. lesion diagnosis: a systematic review of the use of clinical images from their practices. Med Jacob R. 1990. Ramanujam nongynecologic specimens: a pilot study. Bouquot JE. Lee JJ. Fluorescence spectroscopy of oral tissue: precancers. Oral Oncology 2008. Muñoz-Corcuera M. 292:615-640. 274. Ibrahim R. 1877. systems in oral precancers: predictive value. ment. oral cavity neoplasia based on autofluores- ous and cancerous oral lesions. Cancer following ichthyosis of the Vision enhancement system for detection of tongue. England. Die idiopathischen 19. 104:19494-19499. Houston. Stepp H.S. Driemel O. 42(8):810-818. Reibel J. Oral Patol Oral Cir Bucal 2009. ert TE. N. 36: 25-29. 51:788-794. 37:1-10. Prognosis of oral premalignant 28. Utility of toluidine blue in oral premalignant 39. Bouquot JE. Malignant trans. 3:88-90. 61:373-381. Stoltze techniques for oral cancer examination and Cancer Center (Houston.139:896-905. Ann M. White JG. McDonald G. Bouquot JE. 12:11-21. weaknesses and scope for improve. Queries and responses tion within the oral cavity: the use of field 31. Bouquot J. 26. Dysplasia scoring 22. from the Medical Committee of the Society for mapping biopsies’ in clinical manage- et al. J Am Dent Assoc 2008. Natural history coletti R. 18. Sciubba JJ. Roblyer D.D.43:20-26. Hsue S-S. Mehlmann M. troscopy of normal and malignant mucosa Edinburgh Med Surg J 1806. Accessed 9/10/09 1. Michael CW. London. Epstein JB. Zeng H. 3. Oral leuko- manufacturers of products discussed. 65:424-426. Laskin DM. Bouquot JE. Philadel. Gillenwater AM. up study based in a Taiwanese hospital. 133:272. Bascones. tinuing research and implications for clinical in screening for oral premalignant lesions in formation in 1458 patients with potentially practice. 29. Simms. Oral Maxillofac Surg 2007. Damm D. Rick K. lighting: an adjunct for oral mucosal exami- no other financial assistance from any of the nations. Oral Oncol 2007. Canada) and Dr. Gray M. Gen Dent 2009. Speight PM. In vivo multiphoton microscopy of NADH 6. Riching KM. Sensitiv- 11. Oral Med Oral Pathol 1986. Gold L. Zuluaga Quint Internat 1994. Kortum R. Guggenheimer J: Thermally induced assisted analysis of the oral brush biopsy. in suspicious lesions of the oral mucosa. oral-cavity. Arch 34. Lin lesions and squamous cell carcinoma: con- ity of direct tissue fluorescence visualization C-C. malignant oral mucosal disorders: a follow- 25. Huff K. Hamadah O. Sloan P: Potential applications of epithelia. Stark PC. Elley K. Navone R. Amanda Burls A. Epstein JB. 25:133-140. Kerr AR. Pentenero M. Efficacy of the ViziLite review of the autofluorescence section of this lesions: Significance of clinical. Kurachi C. Center (Vancouver. El-Naggar A. 27. oral brush cytology with liquid-based tech- 35. Computer. Richards-Kortum R. Svistun E. cal and molecular biological characteristics. Eliceiri KW. J Clin Dent 2006. References 16. al. Oral Med Oral Pathol 70:597-599. Whitehead TGP. J paper. of potentially malignant oral lesions and of liquid-based oral cytology on the diagnosis 36. Lin L-M. Farthing PM. TriPath PREP liquid-based preparations in Dermat Syph 9:611-570. Epstein JB. Gil. West Mid- 38. Adjunctive lenwater of The University of Texas M. Cano-Sánchez J. Acta Cytol 2007. HY. Ephros H. oral neoplasia using autofluorescence imaging. 3rd edition. 4. Richards- pathology of oral cancer and precancer mucosa. utility. Oral Surg 33. 18(6):356-360. Analysis of new diagnostic methods 32. B. general practice. Hullmann M. Solomon LW. Warnakulasuriya S. system in the identification of oral lesions. 13. 38:161-166. Schwimmer. 2005. 8. Gupta A. 57:34-38. Broc. ing in general dental practice. Cancerisa. Curr Diag Path 2006. Bouquot et al Disclosure 12. weaknesses and scope for improvement. of oral squamous dysplasia and carcinoma. Sciubba J. Andrés F. Speight PM. Bouquot JE. Proceedings. Anicotine@ stomatitis: a case report. Pecott J. Lasers Surg Med 1999. Wil- utility. Rogatsky GG. liams MD. histopathologi. Bailey A. literature. Erythropla. and cellular morphology in precancerous Americans over the age of 35 years. Kerr AR. Head Neck 2007. cence. Reich. Whitaker SB. Skala MC. nostic aids for the detection of oral can- 9. Catherine Poh of the British Columbia Cancer Crit Rev Oral Biol Med 2003. Sargent A. Kujan O. Anderson 15. 126:528-535. planus and other oral keratoses in 23. Trans Clin Soc Lond 1870. Allen C. Gorlin RJ. Mehrotra R. Pract cal evaluation of chemiluminescent over several recent years but have received Perio Aesth Dent 1995. WHO Workshop on oral 23. Head Neck 2004. et al. 2008. Physiol Cell Physiol 2007. Cytopathology 2007. Collaborative OralCDx Study Group. Reibel J. Schwarz RA. J Oral Pathol Med 2009. Objective detection and delineation of revisited. Oral cytology revisited. Pich A. Singh M.com. Wang W-C. 17. 25:323–334. Bouquot JE. Holmstrup P. 36:262-266. The clinical effectiveness of toluidine blue Monte Carlo modeling with site-specific tissue 10. Betz CS. Clini- The authors have used free samples and devices kia: the dangerous red mucosa. Am J 5. Gillenwater A. 2. Martínez A. 14:210-216. dye as an adjunct to oral cancer screen. Desai M. 26:205–215. Stepanek V. Alizadeh-Naderi R. Huber MA. Burlo P. et Acknowledgements nosis of its clinical subtypes or “phases”. Gendron-Fitzpatrick A. J Biomed Opt 2009. biopsy in precancerous and cancerous oral lesions. Williams MD. Lingen MW. J Oral Pathol Med 2008. McConnel J. Mehrotra R. Napier SS. Oh ES. Silverman S Jr. Gandolfo S: The impact Cancer Prev Res (Phila Pa) 2009.