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1What about new waysof detecting potentially

malignant lesionsearlier?

Critical Evaluation of Diagnostic Aids forthe Detection of Oral Cancer*

M Lingen, J Kalmar, T Karrison & P Speight

Oral Oncology 2008 Jan;44(1):10-22University of Chicago, Ohio State University, University of Sheffield

* A position paper of theAmerican Academy of Oral and Maxillofacial Pathology

True Positive and TrueNegative Requires a

GOLD STANDARDGOLD STANDARD for

tissue diagnosis is ascalpel biopsy

Screening vs. Case-FindingCase-finding - a diagnostic test fora patient who has abnormal signs orsymptoms (Class I)

Screening - checking for a disease in aperson who is symptom free (Class II)

Evidence ofchemiluminescenceenhancing intraoral

examinations?Lets look at the scientific

literature

2Evidence of chemiluminescenceenhancing intraoral

examinations?Literature was only for

gynecologicalexaminations until 2004

Acetic Acid Wash and Chemiluminescent Illumination asan Adjunct to Conventional Oral Soft Tissue Examination

for the Detection of Dysplasia: A Pilot StudyHuber MA, Bsoul SA, Terezhalmy GT

Quintessence International 2004: 35(5):378-84

150 consecutive patients Examined linea alba, leukoedema, hairy tongue, leukoplakia, traumatic

ulcer, fibroma, amalgam tattoo, tori and frictional keratosis All 32 cases of leukoedema were positive (aceto-white) - False Positives 2 of 14 frictional keratoses were positive; No biopsies performed on

frictional keratoses 3 Leukoplakias

1 biopsied = hyperkeratosis2 brushed, 1 atypical biopsied = ulcer

One lesion aceto-white lesion identified not clinically apparent

Strengths of this study Large sample size Consecutive patients One lesion detected by ViziLite (not stated what diagnosis was)

Weaknesses of this study

Few cases with histologic correlation Cant assess sensitivity, specificity or predictive value High false positives - suggests that sensitivity may behigh but specificity and PPV are low

Chemiluminescence as a diagnostic aid in the detection oforal cancer and potentially malignant epithelial lesions

Ram, S. and Siar, C.H.Int J Oral maxillofac Surg, 2005;34: 521-527

Study was of already discovered lesions and 5 cases of normaloral mucosa

Comparison to 1% tolonium chloride (toluidine blue) mouthrinse

Negatives were not biopsiedHigh sensitivity, very low specificity (14.2% Vizilite and 25%

tolonium chloride)

This was not a study of efficacy for using Visilite as a screeningmethod

Evidence of chemiluminescence enhancingintraoral examinations?

In our study we have examined only overtly obviouscases of oral cancer which do not require specialscreening tests for identification. In this respect, wehave not been able to detect any case of early oralcancer (CIN) in normal-looking oral mucosa with thistool. The other shortcoming is the observed falsepositive rate of 6/31 lesions indicating the Vizilite isnon-specific and likely to result in many unnecessarybiopsies

S. Ram and C.H. SiarFaculty of Dentistry

University of Malaya

The efficacy of oral lumenoscopy (ViziLite) invisualizing oral mucosal lesions.

Epstein JB, Gorsky M, Lonky S, Silverman S Jr,Epstein JD, Bride M.

Special Care Dentist 2006 Jul-Aug;26(4):171-4College of Dentistry and Illinois Cancer Center, University of Illinois

3All patients had history of previously-detected oralmucosal lesions - Not screening

2 occult lesions in separate patients with previous hx ofsquamous cell carcinoma - one recurrent Ca, one benign

The chemiluminescent light did not appear to improvevisualization of red lesions, but white lesions and lesionsthat were both red and white showed enhancedbrightness and sharpness.

Conclusion:ViziLite examination did notsignificantly improve lesiondetection compared to COE

Weakness:Lack of standardized correlation ofclinical findings to histopathologic

diagnosis of lesional tissue

Clinical evaluation ofchemiluminescent lighting: an adjunct

for oral mucosal examinationsKerr AR, Sirois DA, Epstein JB.

J Clin Dent2006; 17(3):59-63

The Bluestone Center for Clinical Research, NewYork University College of Dentistry

Aim: Describe the utility of Vizilite as aadjunct to visual examination, especially those

lesions clinically suspicious forpre-cancer or cancer

501 patients with positive tobacco history410 suspicious lesions in 270 patients by visualexamination [suspicious for WHAT?]127 lesions suspicious for oral cancer98 were aceto-white + 6 not seen visually77 (78.5%) were suspicious [what happened to 50suspicious lesions?]

ResultsSuggest that Vizilite, when used as a screeningadjunct provides additional visual informationLeukoplakias may be more readily observedOnly sharpness was significantly improvedStudies are underway to explore the clinicalsignificance and predictive value of oralchemiluminescence lighting

NO BIOPSIES WERE PERFORMEDTHIS IS NO HELP WHATSOEVER -

NO IDEA WHAT THE 6 LESIONS DETECTED BYVIZILITE WERE

A pilot case control study on the efficacy of aceticacid wash and chemiluminescent illumination

(ViziLite) in the visualisation of oral mucosalwhite lesions

Camile S. Farah, and Michael J. McCulloughOral Oncology 2007 Sep;43(8):820-4

Department of Oral Medicine and Pathology, School of Dentistry, TheUniversity of Queensland, Brisbane QLD 4072, Australia

School of Dental Science, The University of Melbourne, Melbourne VIC3000, Australia

Received 12 September 2006; revised 17 October 2006; accepted 18October 2006; on-line pub. Dec. 2006

4Strengths:All lesions were biopsied

Weaknesses:2 diagnostic specialists performed all

examinationsCouldnt directly compare clinicaland histological findings for specific

lesions

Aim: Assess efficacy in visualization of oralmucosal white lesions in a tertiary referral center55 pts referred for existent white lesions [not screening]Vizilite subjectively enhanced visualization in 26/55No significant difference in lesion SIZE, EASE OF VISIBILITY, ORBORDER DISTINCTIVENESSCould not distinguish between epithelial hyperplasia, dysplasia, carcinomaor inflammationAll appeared aceto-whiteDid not change provisional diagnosis, nor alter biopsy site

Sensitivity 100%Specificity 0%Accuracy 18.2%

Sensitivity # of true positive results divided by the number of those who have the disease

Specificity # of true negative results divided by the number of

those who are without the disease

Depends on a comparison to a goldstandard

Positive Predictive Value# of true positive results divided by the number of those who tested to have the disease

Negative Predictive Value# of true negative results divided by the number ofthose who tested to be without the disease

Depends on a comparison to a goldstandard Conclusions(Farah and McCullough)

Vizilite does not aid in identification of malignantand potentially malignant oral lesionsDoes not discriminate between keratosis,inflammation, malignant or potentially malignantlesionsLittle if any benefit for lesions already detectedHigh index of suspicion, expert clinical judgementand scalpel biopsy is still essential for proper patientcare

5Efficacy of the ViziLite System in theIdentification of Oral Lesions

Oh, ES and Laskin, DM

J Oral Maxillofac Surg 2007 Mar;65(3):424-6School of Dentistry, University of North Carolina, Chapel Hill, NC

100 patients39 males

61 femalesOral exam with incandescent light - 29 clinically

undiagnosable lesions

Oral exam with acetic acid rinse - 3 additionalclinically undiagnosable lesions

Oral exam with ViziLite - no additional clinicallyundiagnosable lesions

32 clinically undiagnosable lesions were examined withOral CDx

2 were atypical and were biopsiedNeither was premalignant or malignant

Conclusions: Although the acid rinseaccentuated some lesions, the overall detection

rate was not significantly improved. Thechemiluminescent light produced reflections

that made visualization more difficult and thuswas not beneficial.

32 clinically undiagnosable lesions were examined withOral CDx

2 were atypical and were biopsiedNeither was premalignant or malignant

Conclusions: Although the acid rinseaccentuated some lesions, the overall detection

rate was not significantly improved. Thechemiluminescent light produced reflections

that made visualization more difficult and thuswas not beneficial.

Vizilite My opinion at this time

Extra time and care using the systemARE VALUABLE

Evidence of aiding detection of premalignantlesions is quite sparse

Unclear what added benefit there is topractitioner

Cannot discriminate indolent lesions frombiologically worrisome

Not worth charging the patient extra money over astandard visual and tactile exam

Vizilite is NOT approved by the ADA Council on Scientific AffairsIf you do the Vizilite exam, how would you justify charging your patientbased on peer reviewed evidence?

Well-controlled clinical trials are needed that specifically investigate theability of ViziLite to detect precancerous lesions that are invisible by COEalone. Studies needed for combined ViziLite and toluidine blue dye.If such discrimination can be confirmed, it would support the use of thistechnology as a true screening device

Vizilite My opinion at this time(2)

6VELscopeA Magic Wand for the Community Dental Office?

Observations from theBritish Columbia Oral CancerPrevention Program

Laronde D, Poh C, Williams P, Hislop T, Zhang L, MacAulay C, and RosinM.

J Canadian Dent Assoc Sept 2007 (73)7; 607-609

Loss of fluorescence occurs in many benign mucosal conditions, such asgeographic tongue, aphthous ulcers (sic) and tissue trauma.Training in communication skills directed at reducing patient anxietyrelated to abnormal screening result is also important.

VELscopeThe use of the device encouraged greater attention to oral cancer screeningin their practices, leading to the identification of lesions that may have beenotherwise overlooked.

ConclusionsFV has the potential to be an adjunctive screening tool that facilitates thediscrimination of soft tissue changes requiring follow-up.It will not replace conventional clinical examination.Although evidence supports its use in high-risk clinics, its value in generalpractice remains to be determined.No current evidence that using FV in general dental practice saves lives, butregular use of a high quality screening examination could make a difference.

VELscopeEvidence-Based Decision-Making: Should the General

Dentist Adopt the Use of the VELscope for RoutineScreening for Oral Cancer?

Balevi BJ Canadian Dent Assoc Sept 2007 (73)7; 603-606

4 clinical papers reviewed and critically appraised, 2 case studies, 2observational studiesAll studies included patients seen in referral clinics that are specialized inthe diagnosis and management of oral pathologyRisk of test-referral bias

VELscope2 case studies demonstrated potential benefit during follow-up of alreadydiagnosed (high-risk) patients to check for new lesions2 observational studies may be giving an artificially high true-positive rate(sensitivity) and true-negative rate (specificity) because of spectrum biasNo evidence this device can distinguish between oral cancer and aphthousulcers (sic), lichen planus, pemphigoid, etc.No long-term evidence that this device actually saves livesIt is important to consider the potential risk of harm from a false-positivereadingNo assessment of inter-observer and intra-observer agreement

VELscopeShortcomings

Currently, neither the scientific evidence nor the levelof clinical skill justifies the routine us of the VELscopein a general dental practiceThe device is more likely to detect the more commonabnormal oral tissue lesions than oral cancerNo intra- and inter-operator agreement has beenverified

VELscopeConclusions

No evidence that routine use saves livesConcern about the risk of harm if routinelyusedRoutine use is prematureVELscope may be of value in a clinic that isspecialized in management of oral cancer

7VELscopeMy opinion at this time

Best use is in determining margins for excisionsof premalignant lesionsCould be useful in screening if shortcomingscited in the article can be corrected A cell-based sensor to detect oral cancer biomarkers,

such as the epidermal growth factor receptor (EGFR)whose over-expression is associated with early oraltumorigenesis and aggressive cancer phenotypes.

Cell-based sensor for analysis of EGFRbiomarker expression in oral cancer

Shannon E. Weigum, Pierre N. Floriano, NicolaosChristodoulides and John T. McDevitt

Lab Chip, 2007, 7, 995 - 1003

The lab-on-a-chip (LOC) sensor utilizes an embedded track-etched membrane, which functions as a micro-sieve, to captureand enrich cells from complex biological fluids or biopsysuspensions.

Immunofluorescent assays reveal the presence and isotype ofinterrogated cells via automated microscopy and fluorescentimage analysis.

Using the LOC sensor system, with integrated capture andstaining technique, EGFR assays were completed in less than10 minutes with staining intensity, homogeneity, and cellularlocalization patterns comparable to conventional labelingmethods.

These results support the LOC sensor system as a suitableplatform for rapid detection of oral cancer biomarkers andcharacterization of EGFR over-expression in oral malignancies.Application of this technique may be clinically useful in cancerdiagnostics for early detection, prognostic evaluation, andtherapeutic selection

Examples of what you can do with the LOC

* Real-time PCR ;detect bacteria, viruses and cancers. * Immunoassay ; detect bacteria, viruses and cancers based

on antigen-antibody reactions. * Dielectrophoresis detecting cancer cells and bacteria. * Blood sample preparation ; can crack cells to extract

DNA. * Cellular lab-on-a-chip for single-cell analysis. * Ion channel screening

Salivary diagnostics for oral cancer David T. Wong

J Calif Dent Assoc. 2006 Apr;34(4):303-8two salivary proteins, interleukin (IL)-8 and thioredoxin, that

can discriminate between saliva of oral cancer and controlsubjects.

IL-8 is significantly elevated in saliva of oral cancer patientsand is highly discriminatory of detecting oral cancer in saliva

(n = 64) with an receiver operator characteristic (ROC) value of0.95, sensitivity 86% and specificity 97%

Other results suggested that saliva thioredoxin is a validatedbiomarker for oral cancer detection

8UCLA Oral Fluid Nanosensor

Biopsy versusother methods of

analyzing oraltissues

The Brush Test is acase-finding test, not

a screening test

Brush Testexfoliative cytology

PROS No anesthesia Patient

acceptance

CONS Negative results are not

biopsied ? trust ? No research on negatives Negative results were not

tested against the goldstandard



acceptance

CONS(continued) No diagnosis Positive or Atypical

results still need to bebiopsied delayed diagnosis extra cost



acceptance

CONS(continued) Extremely high number

of false positives

9Brush Testexfoliative cytology


acceptance

CONS(continued) No ability to detect

dysplasia byarchitecture

No baseline histology iffuture biopsies are done


ADA Council on Scientific Affairs

All Oral CDx atypical or positiveresults must be confirmed by incisional

biopsy and histology to completelycharacterize the lesion.



Persistent lesions, even with negativeresults, must receive adequate

follow-up evaluations.




follow-up evaluations.




follow-up evaluations.????????????


Shows promiseStudy needed with a large cohort of Class II subjects with

brush and biopsy of ALL subjectsBrush Test may be beneficial:

1. Multiple lesions, particularly in someone with nohistory of oral cancer2. Non-compliant patient who is unlikely to come back fora follow-up exam or accept an immediate biopsyJudicious use in these scenarios may be clinically useful

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