Screening for oral cancer

 

Evidence-Based Clinical Recommendations Regarding Screening for Oral Squamous Cell Carcinomas

 

Michael P. Rethman, DDS, MS, William Carpenter, DDS, MS, Ezra E.W. Cohen, MD, Joel Epstein, DMD, MSD, FRCD(C), FDS RCS(Ed), Caswell A. Evans, DDS, MPH, Catherine M. Flaitz, DDS, MS, Frank J. Graham, DMD, Philippe P. Hujoel, MSD, PhD, John R. Kalmar, DMD, PhD, Wayne M. Koch, MD, Paul M. Lambert, DDS, Mark W. Lingen, DDS, PhD, Bert W. Oettmeier Jr., DDS, Lauren L. Patton, DDS, David Perkins, DMD, Britt C. Reid, DDS, PhD, James J. Sciubba, DMD, PhD, Scott L. Tomar, DMD, DrPH, Alfred D. Wyatt Jr., DMD, Krishna Aravamudhan, BDS, MS, Julie Frantsve-Hawley, RDH, PhD, Jennifer L. Cleveland, DDS, MPH, Daniel M. Meyer, DDS; AND for the American Dental Association Council on Scientific Affairs Expert Panel on Screening for Oral Squamous Cell Carcinomas

Oral Cancer ABSTRACT

Background. This article presents evidence-based clinical recommendationsdeveloped by a panel convened by the American Dental AssociationCouncil on Scientific Affairs. This report addresses the potentialbenefits and potential risks of screening for oral squamouscell carcinomas and the use of adjunctive screening aids tovisualize and detect potentially malignant and malignant orallesions.

Types of Studies Reviewed. The panel members conducted a systematicsearch of MEDLINE, identifying 332 systematic reviews and 1,499recent clinical studies. They selected five systematic reviewsand four clinical studies to use as a basis for developing recommendations.

Results. The panel concluded that screening by means of visualand tactile examination to detect potentially malignant andmalignant lesions may result in detection of oral cancers atearly stages of development, but that there is insufficientevidence to determine if screening alters disease-specific mortalityin asymptomatic people seeking dental care.

Clinical Implications. The panel suggested that clinicians remainalert for signs of potentially malignant lesions or early-stagecancers while performing routine visual and tactile examinationsin all patients, but particularly in those who use tobacco orwho consume alcohol heavily. Additional research regarding oralcancer screening and the use of adjuncts is needed.

Key Words: American Dental Association (ADA); biopsy; brush; cancer; carcinoma; squamous cell; evidence-based dentistry; mouth neoplasms; oral cancer; practice guidelines

Abbreviations: ACS: American Cancer Society • ADA: American Dental Association • CDC: Centers for Disease Control and Prevention • HPV: Human papillomavirus • IR: Incidence rate • LED: Light-emitting diode • RCT: Randomized controlled trial

The American Cancer Society (ACS) estimated that there wouldbe 35,720 new cases of cancer of the oral and pharyngeal regionin the United States in 2009, with 7,600 deaths from the disease.1 When focusing specifically on the oral cavity, ACS estimatedthat in 2009, there would be 23,110 new cases of cancer of theoral cavity (hereafter referred to as “oral cancer”) and 5,370deaths.1 Nearly 90 percent of these malignancies are squamouscell carcinomas.2 More than 97 percent of U.S. cases of thesecancers occur among adults 35 years and older.3 Although theincidence rate (IR) of oral and pharyngeal cancers is decreasingoverall, the IR of cancers of the tongue, oropharynx and tonsilis increasing.3 The 2002–2006 age-adjusted (to the 2000U.S. population) IR of oral and pharyngeal cancers in the UnitedStates was 10.3 per 100,000 per year. The age-adjusted IR wasmore than twice as high among men (15.9) as among women (6.0),as was the mortality rate (men, 4.0; women, 1.5).3

Among the groups described in data from the National CancerInstitute’s Surveillance Epidemiology and End Resultsprogram,3 African-American men are at the highest risk of developingoral and pharyngeal cancers of any group in the United States(IR 16.7 per 100,000 per year).3 The five-year relative survivalrate varies widely by stage at the time of diagnosis, from 81.8percent for patients diagnosed in localized stages and 52.1percent for patients with regional lymph node involvement to26.5 percent for patients with distant metastasis.3 Yet, oraland pharyngeal cancer is diagnosed at a localized stage in onlyone-third of patients in the United States.3 The overall five-yearrelative survival rate for the 1999–2005 period was 61.0percent and varied significantly by race (62.4 percent for whitemen and 38.2 percent for black men).3 Much of the racial disparityin survival rates was due to the greater proportion of tumorsdiagnosed at late stages among black men than among white men.3

Oral Cancer SCOPE AND PURPOSE OF THE RECOMMENDATIONS

 

This report was developed by a panel convened by the AmericanDental Association (ADA) Council on Scientific Affairs to addressthe benefits and limitations of oral cancer screening and theuse of adjunctive screening aids to visualize and detect potentiallymalignant and malignant oral lesions. The panel’s workwas supported in part by the Centers for Disease Control andPrevention (CDC), Atlanta.

We have excluded squamous cell carcinomas of the lips from thisarticle, because the risk factors, stage-at-diagnosis patterns,morbidity and mortality of those carcinomas differ from thoseof cancer in sites in the oral cavity. We also excluded fromthis report cancers of the oropharynx (including the posteriorone-third [base] of the tongue and the tonsils). Although theoral cavity and the oropharynx overlap in the region of thehard and soft palate and tonsils, recent systematic reviewssuggest that human papillomavirus (HPV) is a risk factor forcancers of the base of the tongue and the tonsils.4–6In contrast, HPV does not appear to be a significant risk factorfor cancer of the anterior two-thirds of the tongue or the remainingoral cavity. The importance of this distinction is highlightedby evidence that HPV-related carcinomas have a better prognosisoverall than do non-HPV–related carcinomas.7,8

The clinical recommendations in this article, which presentsa critical evaluation and summary of the relevant scientificevidence, do not represent a standard of care. Instead, thisreport is intended to assist the clinician in the decision-makingprocess. Its clinical recommendations should be integrated withthe practitioner’s professional judgment and the individualpatient’s needs and informed preferences.

Table 1Go presents definitions of the terms used in this report.

 

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 TABLE 1 Definitions of terms used in this report.
Oral Cancer ORAL CANCER SCREENING: DEFINITION AND CONTEXT

 

This report defines “screening” as the process by which a practitionerevaluates an asymptomatic patient to determine if he or sheis “likely” or “unlikely” to have a potentially malignant ormalignant lesion. In “mass screening” programs, also known as”community-based” or “population-based” screening, the targetgroup is invited to participate specifically for the purposeof detecting potentially malignant lesions. These screeningsmay have a specific goal of detecting potentially malignantoral lesions, or they may be broader in scope and involve assessmentof a person’s general oral health status. In a dentalsetting, the act of “screening” for oral cancer occurs whena patient reports for care. This often is referred to as an”opportunistic screening.”

The practitioner obtains a health history to assess the patient’sgeneral health and risk of developing disease. A thorough healthhistory review should yield information about the patient’stobacco and alcohol use, hospitalization history, surgery experience,dietary patterns, medication regimen and other illnesses.9 Investigatorshave observed an increased risk of developing oral cancer withincreasing age,3 in people who use tobacco,10 in people whoconsume alcohol heavily (for men an average of more than twodrinks daily and for women an average of more than one drinkdaily),10,11 in people who have a history of upper aerodigestivetract cancer12–14 and in people who have certain inheriteddiseases, such as Fanconi anemia.15–17 The practitioneralso conducts a visual and tactile examination (referred toas “examination” throughout this report) to detect the presenceof any oral abnormality. Some of the mucosal abnormalities notedon examination could be a potentially malignant or malignantlesion. This examination should not be viewed as a series ofdistinct subsegments intended to detect individual diseases.Screening for oral cancer is but one component of the comprehensivepatient evaluation provided by dentists to detect all formsof oral pathoses, including those of neoplastic, infectious,reactive/inflammatory or developmental origin.

Clinical signs of cancer. Invasive cancer. Clinical signs of invasive cancer can include induration; persistentulceration; tissue proliferation or destruction; red and whitecolor variegation; lack of mucosal mobility; progressive growthor enlargement of the affected site; pain or dysesthesia, paresthesiaor loss of function; and cervical lymphadenopathy. Most oralsquamous cell carcinomas exhibit one or more of these clinicalsigns, which often are identifiable on routine examination.

Early-stage cancer. Clinical features of oral lesions identified during a routinevisual and tactile examination that might raise suspicion ofpotential malignancy include sharp or distinct margins, a redcomponent (color variation), a non-homogenous white component(surface irregularity), persistent ulceration and size largerthan 1 centimeter. The clinician also should view with suspicionany persistent or progressive lesion of the ventrolateral tongueor the floor of the mouth (both of which are high-risk sitesfor oral squamous cell carcinoma).

Early-stage lesions often are asymptomatic and may mimic otherconditions, whereas others may not be readily evident in routineexamination. Also, because malignant and benign lesions maynot be clinically distinguishable,18 the clinician cannot predictthe biological relevance of lesions on the basis of their physicalfeatures alone.

Oral Cancer ADJUNCTIVE SCREENING AIDS

 

Adjunctive screening aids are marketed to assist clinicianswith the detection of early cancerous changes or for the assessmentof the biological relevance of mucosal lesions.

Devices intended to assist in lesion detection. These devices feature special light sources designed accordingto principles of tissue reflectance and tissue autofluorescenceto enhance the oral examination process. Manufacturers of thesedevices claim that they may help the practitioner to visualizeoral mucosal abnormalities that are not readily detectable withconventional operatory lighting, or that they can enhance thepractitioner’s ability to specifically identify potentiallymalignant lesions.

Devices based on tissue reflectance. These devices are claimed to help practitioners detect oralmucosal abnormalities that otherwise would be difficult to discernon routine visual examination. The following commercial tissue-reflectance–baseddevices are available in the United States: Microlux/DL (AdDent,Danbury, Conn.), Orascoptic DK (Orascoptic, a Kerr Company,Middleton, Wis.) and ViziLite Plus (Zila Pharmaceuticals, adivision of Tolmar, Phoenix).

ViziLite Plus uses a disposable chemiluminescent light packet,and the MicroLux/DL and Orascoptic DK units use a reusable,battery-powered light-emitting diode (LED) light source thatprovides a similar blue-white (440-nanometer range) illumination.19 Each system employs a 1 percent acetic acid wash before useof its respective light source. Under blue-white illumination,abnormal squamous epithelium is reported to be distinctly white(acetowhite).20 ViziLite Plus also provides a toluidine bluesolution (TBlue, Zila Pharmaceuticals), which is intended tomark an acetowhite lesion for subsequent biopsy.

The MicroLux/DL and Orascoptic devices use a similar reusableinsert or probe to transmit light from the LED source in thehandpiece to the oral tissues.21,22 Both units are marketedas multiuse devices because their handpieces are designed toaccept a separate transillumination tip for detection of toothfractures or caries, as well as another insert that providesthe dentist with a lighted mirror.21,22

Device based on autofluorescence. VELscope (LED Dental, Burnaby, British Columbia, Canada) ismarketed as an adjunct to visual examination in the identificationof oral mucosal abnormalities that otherwise may not be apparentwith conventional operatory lighting. Under the blue-light excitation(400–460 nm) provided by the unit, normal oral mucosaemits a pale green autofluorescence when viewed through thefilter set incorporated within the handpiece. In contrast, themanufacturer states that abnormal tissue exhibits decreasedlevels of autofluorescence and appears dark compared with thesurrounding tissue.23 The manufacturer cautions, however, thatloss of autofluorescence is not limited strictly to epithelialabnormalities and can be seen with prominent surface vascularity,including areas of inflammation, and melanin pigmentation.23

Device based on autofluorescence and tissue reflectance. Identafi 3000 (Trimira, Houston) combines the technologies oftissue reflectance and autofluorescence with a conventionalwhite light source.24 It is claimed to help the practitioneridentify oral mucosal abnormalities that otherwise may not beapparent.24 It also is claimed to help the practitioner discernthe superficial vascularity of the tissue.24

Device intended to assist in lesion assessment. This type of device is designed to help practitioners assessthe biological relevance of mucosal lesions and determine theneed for surgical biopsy and tissue diagnosis. By providinga transepithelial (full-thickness) collection of disaggregatedcells from the lesional tissue, the device allows subsequentidentification of atypical cells that may indicate malignancy.

Device based on transepithelial cytology. The OralCDx BrushTest (OralCDx Laboratories, Suffern, N.Y.)is intended for the evaluation of lesions that do not immediatelyraise suspicion of cancer.25 The Oral CDx BrushTest consistsof a disposable, circular plastic brush that the clinician rubsor rotates against the lesion until he or she observes pinpointbleeding. The clinician uses this clinical endpoint to confirmpenetration of the basement membrane and acquisition of a transepithelial(full-thickness) sample. After the clinician transfers the sampleto a glass slide, he or she applies a fixative solution, thenreturns the fixed sample to the company for computer-assistedanalysis and interpretation by a pathologist.

The specimen analysis will yield one of four results26:

– incomplete specimen—too few cells from all celllayers; 

– negative—no evidence of abnormal cells; 

– atypical—abnormal epithelial cells of uncertainsignificance; 

– positive—definitive evidence ofdysplastic orcancer cells. 

 

In the case of atypical or positive results, the company recommendssurgical biopsy of the lesion. This is because the test resultis limited to reporting the presence or absence of cellularabnormalities and does not provide a final diagnosis.

Oral Cancer METHODS

 

The ADA Council on Scientific Affairs convened a panel to evaluatethe available evidence regarding oral cancer screening and theuse of adjuncts. The Council selected panelists on the basisof their expertise in the relevant subject matter. At a workshopheld at ADA Headquarters April 13–15, 2009, the panelevaluated the published evidence and developed evidence-basedclinical recommendations for oral cancer screening and the useof adjuncts.

Conflict-of-interest disclosures. The panel comprised 20 people who represented a broad rangeof expertise. Each panelist completed a standard conflict-of-interestquestionnaire.

Literature search. Staff members of the ADA Center for Evidence-Based Dentistrysearched MEDLINE through PubMed to identify systematic reviewsthat addressed the four clinical questions. (For informationabout the clinical questions and detailed methods, see Appendix1 in the supplemental data to the online version of this articleat “http://jada.ada.org“.) On the basis of the inclusion and exclusioncriteria, they identified five systematic reviews.27–31They conducted a second search to identify clinical studiespublished after the last search date within the systematic reviews.They identified four additional clinical studies.32–35Appendix 1 in the supplemental data online (found at “http://jada.ada.org“)provides a detailed description of the search methodology andthe inclusion and exclusion criteria, as well as a list of excludedpublications.

Data synthesis and critical appraisal. The panel performed a qualitative synthesis of data from theincluded studies in a narrative format. For the included studies,they performed quality assessment of the individual articlesby using standard U.S. Preventive Services Task Force methodologyfor determining internal and external validity.36 (For informationabout the quality assessment, see Appendix 2 of the supplementaldata to the online version of this article at “http:jada.ada.org“.)The panel asked Drs. Patton and Epstein, authors of a systematicreview of adjunctive screening devices, to update the resultsof their systematic review with data from the three includedclinical studies of screening devices.32,33,35 (For informationabout the update, see Appendix 3 of the supplementaldata tothe online version of this article at “http:jada.ada.org“.)

Grading evidence statements and clinical recommendations. On the basis of the included studies, the panel developed evidencestatements and graded them according to a system developed byShekelle and colleagues37 (Table 2Go). The panel developed clinicalrecommendations based on its interpretation of this evidence.They classified clinical recommendations according to the strengthof the evidence that formed the basis for the recommendation,again by using a system modified from that of Shekelle and colleagues.37 The classification of the recommendation directly reflectsthe level of scientific evidence that supports the recommendation.

 

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 TABLE 2 Grading evidence statements and clinical recommendations.*

 

Process for developing clinical recommendations. When the panel was unable to reach a consensus when translatingevidence into clinically relevant recommendations, it used amajority vote to make final determinations.

Review process. The panel submitted its clinical recommendations for commentto both internal and external scientific experts and organizations.After reviewing all submitted remarks, the panel revised itsrecommendations where appropriate. (For information about theexternal reviewers, see Appendix 4 of the supplemental datato the online version of this article at “http:jada.ada.org“.)The ADA Council on Scientific Affairs approved the final clinicalrecommendations.

Role of the funding source. The work of this panel was commissioned by the Council on ScientificAffairs and was funded jointly by the ADA and CDC.

Oral Cancer DISCUSSION

 

The panel came to the following conclusions on the basis ofthe evidence. The corresponding grade of evidence appears inparentheses.

– While stage of cancer at diagnosis has an impact ontreatment decisions and resultant health outcomes, community-basedscreening by means of visual and tactile examination in thegeneral adult population intended to detect early and advancedoral cancers may not alter disease-specific mortality30 (Ib). 

– Community-based screening by means of visual and tactileexamination may decrease oral cancer–specific mortalityamong people who use tobacco, alcohol or both30 (Ib). 

–Screening by means of visual and tactile examinationmay resultin detection of oral cancers at early stages of development(stages I and II)30,34 (Ib). 

– In asymptomatic patientsseeking dental care, thereis insufficient evidence to determinewhether screening by meansof visual and tactile examinationto detect potentially malignantand malignant lesions altersdisease-specific mortality28 (III). 

– There is insufficientevidence that commercial devicesbased on autofluorescence enhancevisual detection of potentiallymalignant lesions beyond thatachieved through a conventionalvisual and tactile examination27 (III). 

– There is insufficient evidence that commercialdevicesbased on tissue reflectance enhance visual detectionof potentiallymalignant lesions beyond that achieved througha conventionalvisual and tactile examination27 (III). 

–There is insufficient evidence to assess the validityof transepithelialcytology of seemingly innocuous mucosal lesions27 (III). 

–In suspicious mucosal lesions with high potential formalignancy,transepithelial cytology has validity in identifyingdisaggregateddysplastic cells27 (III). 

 

A conclusion of “insufficient evidence” does not necessarilymean that the intervention is or is not effective, but insteadmeans that the panel did not find sufficient evidence to supporta recommendation.

Table 3Go is a summary of the expert panel’s conclusions.The boxGo (page 516) presents the panel’s recommendationsfor research.

 

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 TABLE 3 Recommendations of the American Dental Association Council on Scientific Affairs Expert Panel on Screening for Oral Squamous Cell Carcinomas,* based on evidence.

 

 

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 BOX Recommendations for research.

 

Rationale for recommendations: oral cancer screening. Screening by means of examination can detect potentially malignantand malignant lesions at an early stage.30,34 Yet just as clinicalfeatures alone cannot reliably distinguish between benign andmalignant lesions,38,39 neither can the clinician accuratelypredict the likelihood or rate of progression to cancer (malignanttransformation) for a given potentially malignant lesion onthe basis of routine biopsy, histopathological examination anddiagnosis.40 Further complicating matters is the relativelylow prevalence of potentially malignant and malignant oral mucosallesions in the general U.S. population. In relatively rare diseases,only a small proportion of lesions that yield positive screeningresults will be true positives, even when the clinician usesa screening test with high sensitivity and specificity.

Researchers who conducted a randomized controlled trial (RCT)in India suggested that screening by means of visual and tactileexamination to detect potentially malignant lesions may notlower the disease-specific mortality rate in the general adultpopulation, even in a country such as India, which has a higherprevalence rate of oral cancer than does the United States.41The evidence also suggested that a community-based screeningprogram (that is, examination of a target group of people whoseparticipation is solicited via invitation) that identified peoplewith early and advanced stages of the disease in the generaladult population may not lower mortality rates. However, membersof the panel questioned the applicability of this evidence toasymptomatic patients seeking dental care in the United States.

Successful translation of oral cancer screening regimes intoreduced mortality requires that patients receive confirmatorydiagnosis, have continual access to a health care delivery systemand complete a curative treatment regimen. In the India-basedRCT, only 63 percent of the patients whose screenings (by trainedhealth care workers) yielded positive results for leukoplakias,erythroplakias, submucous fibrosis or oral cancer complied withreferral to a physician for confirmation and, if warranted,surgical biopsy.41 Furthermore, in that study, a greater percentageof the cases were diagnosed in stages III and IV of the diseaseas compared with those diagnosed in stages I and II.42 Of the122 patients whose cancer was diagnosed in early stages (stagesI and II), only five were “low-risk” patients (nonusers of tobaccoand alcohol).42 Although these articles did not provide treatmentdetails, the panel contacted the authors to obtain additionalinformation. The authors reported that one-third of patientswho complied with referral did not receive care with intentto treat (Dr. R. Sankaranarayanan and Dr. R. Muwonge, electroniccommunication, Sept. 10, 2009). The lower IR of oral cancerin the United States makes it difficult to perform a similarRCT in this country, which may explain in part the paucity ofU.S. data supporting a positive health outcome resulting fromoral cancer screening.

The extent (stage) of cancer at diagnosis guides treatment.But members of the panel found insufficient evidence to determinewhether screening favorably altered disease-specific outcomes—includingtreatment-related morbidity (such as esthetics, speech and swallowing)—oraffected patients’ quality of life, either positivelyor negatively. Furthermore, in the routine setting of asymptomaticpatients’ seeking dental care, there is insufficient evidenceto determine whether screening by means of visual and tactileexamination to detect potentially malignant and malignant lesionsalters disease-specific mortality.

A disease-screening regimen should include a comparison of therisks of intervention and nonintervention, and the benefitsof intervention and nonintervention. For example, a screeningprogram may fail to detect a disease that otherwise might besuccessfully treated. Screening also may reveal highly aggressivelife-threatening cancers whose outcome may not have been changedby early detection—that is, for which treatment wouldbe futile. In addition, screenings may falsely identify nondiseasedsites as diseased and may detect disease that, if undetected,might not ever interfere with a patient’s life. The lattertwo scenarios can result in needless worry, unnecessary interventionsand wasted resources.

In the context of the limited evidence available, the panelmembers agreed that for oral squamous cell carcinomas, the evidencesuggests that routine oral screenings (consisting of visualand tactile examinations) of asymptomatic patients can detectsome potentially dangerous lesions at earlier stages. This suggeststhe potential for less invasive treatments with less attendantmorbidity and improved mortality—if one makes the plausibleassumption that a number of these early lesions would have progressedhad there been no intervention. As noted previously, however,there is insufficient evidence in this context to determinewhether early detection and treatment alter disease-specificoutcomes, such as morbidity or mortality, or whether screeningaffects patients’ quality of life, either positively ornegatively. Yet, despite the likelihood of biases inherent inthis comparison, the five-year survival rate of patients withearly-stage oral squamous cell carcinomas (stages I and II)is higher than that of patients with cancers detected at later,more advanced stages.

In light of the lack of evidence regarding the effects of routinescreening of asymptomatic dental patients on morbidity or mortalityin the United States, the panel weighed the potential benefitsand the potential risks of such screening in making its recommendations.The panel agreed that routine screening might extend the livesof some patients but also might have associated risks for manyothers. Applying their clinical experiences and professionaljudgment to the available evidence, the majority of the panelmembers concurred that the potential life-saving benefits forthe smaller percentage of patients with treatable malignantlesions was more important than the potential physical and psychologicalharms incurred by the higher percentage of patients with benignor nonprogressive lesions. Because of these considerations,the majority of the panel members stressed the need for cliniciansto remain alert for signs of potential malignancy when performinga routine visual and tactile examination in dental patients,especially those with a history of tobacco and heavy alcoholuse.

Recognizing the need to minimize false-positive screening results,the panel suggested that clinicians follow up with patientswithin seven to 14 days after first removing or treating anypotential cause(s) of lesions to confirm persistence or progressionof lesions, especially in lesions that initially appeared innocuous.Because many oral soft-tissue lesions are transient and willresolve if the suspected etiologic factor is removed or treated(for example, eliminating a local irritant or dental trauma),limiting biopsies to only those lesions that persist may improvescreening accuracy. When a clinician observes a persistent orprogressive lesion, he or she may consider prompt referral toa dental or medical provider with advanced training and experiencein diagnosis of oral mucosal disease before performing tissuebiopsy. This will further limit possible morbidity associatedwith false-positive results. However, should a clinician suspectpotential malignancy in a mucosal abnormality on initial examination,he or she may want to perform a biopsy immediately or ensurethat the patient receives prompt evaluation (and possible biopsy)by a dental or medical care provider who has advanced trainingand experience in diagnosis of oral mucosal disease.

When a definitive diagnosis is needed, a clinician should performa surgical biopsy with subsequent specimen processing and histopathologicalexamination.43 The panel also suggested that clinicians understandand clearly communicate to the patient the benefits of earlydiagnosis and the potential risks to assist the patient in healthcare decision making.44

Visualization devices. In studies published thus far, researchers have evaluated ViziLite,ViziLite Plus and VELscope. There is no published evidence regardingthe utility of MicroLux/DL, Orascoptic DK or Identafi 3000.Overall, there is insufficient evidence that the commerciallyavailable devices based on tissue reflectance (ViziLite andViziLite Plus) and autofluorescence (VELscope) improve the detectionof potentially malignant lesions beyond that of a conventionalvisual and tactile examination.

Clinicians should be aware that understanding the etiology ofcancer along with the differences in clinical presentation ofother similar abnormalities remains of primary importance.

 

Two studies of ViziLite showed the device to have high sensitivitybut low specificity when researchers confirmed its findingsthrough histopathological examination.45,46 There is some evidencethat VELscope may improve the determination of surgical marginsand selection of the optimal biopsy site in large or multifocallesions or during surgery.47,48 The manufacturer has extrapolatedthis evidence to suggest that this device could help identifypotentially malignant lesions that may not be readily apparentor visible to the naked eye.24 However, to our knowledge, nopeer-reviewed publications support this claim. Overall, visualizationaids may affect a lesion’s appearance in terms of brightness,texture and delineation of margins and in patients with previouslydetected lesions,20,49,50 but they have not been shown to enhancethe practitioner’s ability to identify potentially malignantlesions specifically or to identify lesions not visible undernormal operatory lighting. Furthermore, there is insufficientevidence that these devices improve patient compliance or aidin patient education.

As mentioned earlier, a visual examination cannot identify specificallythe small proportion of lesions that exhibit early cancerouschanges. Using currently available visualization aids does notallow a clinician to overcome this limitation. Clinicians shouldbe aware that understanding the etiology of cancer along withthe differences in clinical presentation of other similar abnormalitiesremains of primary importance. Use of these devices can be associatedwith an increased risk of false-positive findings.22 The panelfound insufficient evidence to make a recommendation for oragainst general dentists’ use of these devices in theirpatients.

Transepithelial cytology of disaggregated cells (Oral CDx BrushTest). While results of the Oral CDx BrushTest may help the practitioneridentify the presence of atypical cells in seemingly innocuousmucosal lesions, clinicians must note that atypical findingsfrequently are obtained when this test is performed on inflammatoryor reactive lesions. Receiving an “atypical” test result ismore common when the BrushTest is used on an inappropriate typeof lesion, such as a pigmented mucosal lesion. Application ofthe BrushTest to common mucosal abnormalities that may mimicprecancerous changes clinically, such as reactive frictionalkeratosis, without observation during a follow-up examinationseven to 14 days after initial detection also raises the probabilityof receiving an “atypical” result. These results (essentiallyfalse positives) may lead, in turn, to unwarranted referralof the patient for further evaluation by a dental or medicalcare provider with advanced training and experience in diagnosisof oral mucosal disease; they may even trigger tissue biopsiesthat otherwise might have been deemed unnecessary by practitionerswho have advanced training and experience in diagnosis of oralmucosal disease. Thus, there is insufficient evidence to supporta recommendation for or against the use of Oral CDx BrushTestin seemingly innocuous mucosal lesions.22

In clinically suspicious lesions, the Oral CDx BrushTest hasvalidity in identifying disaggregated dysplastic cells.22 Despitethis, the panel members believe that clinically suspicious lesionsshould be biopsied immediately for a diagnosis. On the otherhand, the panel members believe that the Oral CDx BrushTestmay prove useful for patients in specific clinical situations.These might include patients who have multiple lesions throughoutthe oral cavity and no history of oral cancer (as an alternativeto multiple scalpel biopsies); noncompliant patients who areunlikely to return for follow-up care or comply with an immediatereferral for further evaluation by a dental or medical careprovider who has advanced training and experience in diagnosisof oral mucosal disease51; adults who have physical and intellectualdisabilities or a complex medical status who cannot safely toleratea surgical procedure or who have severe access-to-care restraints;and those who have a history of previously treated upper aerodigestivetract cancer.

Stand-alone use of toluidine blue. Toluidine blue (also known as tolonium chloride) is a vitaldye that differentially stains abnormal tissues, including thosethat are premalignant and malignant in nature. While not approvedby the U.S. Food and Drug Administration for use as a stand-aloneadjunct for oral cancer detection in the United States, toluidineblue is used widely in other parts of the world as a means ofassessing mucosal abnormalities for evidence of possible malignantor premalignant changes.

In people with a history of oral cancer or people older than50 years who smoke and drink, toluidine blue may assist dentalor medical care providers who have advanced training and experiencein diagnosis of oral mucosal disease in the clinical assessmentof potentially malignant lesions. However, there is insufficientevidence to recommend for or against the stand-alone use oftoluidine blue to enhance the identification of potentiallymalignant lesions in the general population.

Oral Cancer FUTURE TECHNOLOGIES

 

A number of promising new technologies have been proposed toimprove the effectiveness of early oral cancer detection, includingthe use of saliva as an oral cancer screening platform; theuse of cytology plus ploidy analysis; loss-of-heterozygosityanalysis; identification of bacterial markers in biofilms; identificationof individual or multiple protein biomarkers revealed via tissuebiopsies; the use of in vivo molecular probes and paints; andthe use of other imaging modalities. We have not reviewed thesetechnologies in this article.

Oral Cancer CONCLUSION

 

These recommendations are intended to help practitioners withissues related to assessment and detection of oral cancer. Theyshould not be viewed as rigid guidelines or standards of care,but as evidence-based recommendations to be used together witheach practitioner’s professional judgment and experiencein the context of the needs or informed preferences of the individualpatient. Although the panel formulated these recommendationson the basis of careful review of published scientific evidence,the panel acknowledges that the current literature related tooral cancer screening is not robust. Additional well-designedepidemiologic studies and prospective controlled clinical trialsare needed. Regarding screening adjuncts, the panel found insufficientevidence to support recommendations for or against the use oflight-based technologies compared with conventional operatorylighting alone. While the OralCDx BrushTest has demonstratedvalidity as an adjunct to lesion assessment in specific clinicalsituations, practitioners must remember that the diagnosticgold standard for oral cancers and potentially malignant lesionscontinues to be histopathological examination of surgical biopsyspecimens.

Screening for oral cancer is only one component of a thoroughoral examination and evaluation that includes obtaining a patienthistory and an oral cancer risk assessment. When a mucosal lesionis noted, re-evaluation in seven to 14 days to confirm lesionpersistence can reduce the potential for errors in clinicaldiagnosis. Similarly, the clinician can reduce the risk of performingunnecessary biopsies by obtaining an opinion by a dental ormedical care provider who has advanced training and experiencein diagnosis of oral cancer and its precursor lesions.

 

Oral Cancer FOOTNOTES

 

Dr. Rethman is a periodontist in Honolulu; an adjunct assistantprofessor, College of Dentistry, The Ohio State University,Columbus; and an adjunct assistant professor, Baltimore Collegeof Dental Surgery, University of Maryland. He also is the chair,American Dental Association Council on Scientific Affairs.

 

Dr. Carpenter is a professor and the chair, Department of Pathologyand Medicine, Arthur A. Dugoni School of Dentistry, Universityof the Pacific, San Francisco. He also represented the AmericanDental Association Council on Access, Prevention and InterprofessionalRelations on the expert panel.

 

Dr. Cohen is an associate professor, Department of Medicine,University of Chicago Medical Center.

 

Dr. Epstein is a professor, Department of Oral Medicine andDiagnostic Sciences, College of Dentistry; a professor, Departmentof Otolaryngology—Head and Neck Surgery, College of Medicine;and a professor, Cancer Center, University of Illinois at Chicago.

 

Dr. Evans is the associate dean for prevention and public healthsciences, College of Dentistry, University of Illinois at Chicago.

 

Dr. Flaitz is a professor, Department of Diagnostic Sciences,and a professor, Department of Pediatric Dentistry, Universityof Texas Dental Branch at Houston.

 

Dr. Graham maintains a private practice in orthodontics in Teaneck,N.J., and is a senior attending dentist in orthodontics, Departmentof Dentistry, Montefiore Medical Center, Bronx, N.Y. He alsois the immediate past chair, American Dental Association Councilon Dental Practice, and represented the Council on the expertpanel.

 

Dr. Hujoel is a professor, Department of Dental Public HealthSciences, School of Dentistry, University of Washington, Seattle.

 

Dr. Kalmar is a professor, Division of Oral and MaxillofacialSurgery, Pathology and Anesthesiology, College of Dentistry,The Ohio State University, Columbus. He also represented theAcademy of Oral and Maxillofacial Pathology on the expert panel.

 

Dr. Koch is a professor, Department of Otolaryngology–Headand Neck Surgery, Johns Hopkins Medicine, Baltimore. He alsorepresented the American Head and Neck Society on the expertpanel.

 

Dr. Lambert is the chief of staff, Department of Veterans AffairsMedical Center, Boise, Idaho. He also represented the AmericanAssociation of Oral and Maxillofacial Surgeons on the expertpanel.

 

Dr. Lingen is an associate professor, Department of Pathology,University of Chicago Medical Center. He also represented theAmerican Dental Association Council on Scientific Affairs onthe expert panel.

 

Dr. Oettmeier maintains a private practice in general dentistryin Leawood, Kansas. He also represented the American DentalAssociation Council on Dental Benefits Programs on the expertpanel.

 

Dr. Patton is a professor and the interim chair, Departmentof Dental Ecology, School of Dentistry, University of NorthCarolina at Chapel Hill.

 

Dr. Perkins maintains a private practice in general dentistryin Bristol, Conn. He also represented the American Dental AssociationCouncil on Education and Licensure on the expert panel.

 

Dr. Reid is the chief, Modifiable Risk Factors Branch, Epidemiologyand Genetics Research Program, Division of Cancer Control andPopulation Sciences, National Cancer Institute, Bethesda, Md.

 

Dr. Sciubba is a retired professor and director of dental andoral medicine, School of Medicine, Johns Hopkins University,Baltimore, and a member of the consulting staff, The MiltonJ. Dance Head & Neck Center, Greater Baltimore Medical Center.

 

Dr. Tomar is a professor, Department of Community Dentistryand Behavioral Science, College of Dentistry, University ofFlorida, Gainesville. He also is the president, American Associationof Public Health Dentistry.

 

Dr. Wyatt maintains a private practice in general dentistryin College Park, Ga., and is an assistant professor of oralrehabilitation, School of Dentistry, Medical College of Georgia,Atlanta. He also represented the National Dental Associationon the expert panel.

 

Dr. Aravamudhan is the assistant director, Center for Evidence-BasedDentistry, Division of Science, American Dental Association,211 E. Chicago Ave., Chicago, Ill. 60611, e-mail “aravamudhank@ada.org“.Address reprint requests to Dr. Aravamudhan.

 

Dr. Frantsve-Hawley is the director, Research Institute andCenter for Evidence-Based Dentistry, Division of Science, AmericanDental Association, Chicago.

 

Dr. Cleveland is a dental officer, Surveillance, Investigations,and Research Branch, Division of Oral Health, Centers for DiseaseControl and Prevention, Chamblee, Ga.

 

Dr. Meyer is the director, Division of Science, and the seniorvice president, Science and Professional Affairs, American DentalAssociation, Chicago.

 

Disclosures. Dr. Carpenter has received compensation from OralCDx Laboratories, Suffern, N.Y., for lectures he has presented.Dr. Epstein is conducting an ongoing study with Zila Pharmaceuticals,Phoenix, served on the company’s medical advisory boarduntil 2007 and has given presentations supported by the company.Dr. Flaitz is a research investigator in a clinical trial fundedby Trimira, Houston, investigating the use of the Identafi 3000for the detection of oral lesions, and is a funded presenterfor educating the public about this new device; she was a fundedlecturer for Oral CDx Laboratories; she received “in kind” productsto assist in teaching and for continuing education programsfrom Oral CDx BrushTest (CDx Laboratories), ViziLite (Zila Pharmaceuticals),Identafi 3000 (Trimira), MicroLux/DL (AdDent, Danbury, Conn.)and VELscope (LED Dental, Burnaby, British Columbia, Canada).Dr. Sciubba has received compensation from Oral CDx Laboratoriesfor lectures he has presented. Dr. Wyatt has lectured for andwas compensated financially by LED Dental.

 

The work of the American Dental Association Council on ScientificAffairs Expert Panel on Screening for Oral Squamous Cell Carcinomaswas supported in part by the Centers for Disease Control andPrevention, Atlanta.

 

The findings and conclusions in this report are those of theauthors and do not necessarily represent the official positionof the Centers for Disease Control and Prevention.

 

The American Dental Association Council on Scientific Affairsand this expert panel thank Jane McGinley, RDH, MBA, manager,fluoridation and preventive health activities, American DentalAssociation, Chicago, for her contribution to this project.

Oral Cancer REFERENCES

  • Jermal A, Siegel R, Ward D, Hao Y, Xu J, Thun M. Cancer statistics, 2009. CA Cancer J Clin 2009;59(4):225–249.[Abstract/Free Full Text]
  • Hoffman HT, Karnell LH, Funk GF, Robinson RA, Menck HR. The National Cancer Data Base report on cancer of the head and neck. Arch Otolaryngol Head Neck Surg 1998;124(9):951–962.[Abstract/Free Full Text]
  • Horner MJ, Ries LAG, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2006. Bethesda, Md.: National Cancer Institute; 2009. “http://seer.cancer.gov/csr/1975_2006/“. Accessed March 8, 2010.
  • Termine N, Panzarella V, Falaschini S, et al. HPV in oral squamous cell carcinoma vs head and neck squamous cell carcinoma biopsies: a meta-analysis (1988–2007). Ann Oncol 2008;19(10):1681–1690.[Abstract/Free Full Text]
  • Hobbs CG, Sterne JA, Bailey M, Heyderman RS, Birchall MA, Thomas SJ. Human papillomavirus and head and neck cancer: a systematic review and meta-analysis. Clin Otolaryngol 2006;31(4):259–266.[Medline]
  • Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev 2005;14(2): 467–475.[Abstract/Free Full Text]
  • Ragin CC, Taioli E. Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer 2007;121(8):1813–1820.[Medline]
  • Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 2008;100(4): 261–269.[Abstract/Free Full Text]
  • Sciubba JJ. Oral cancer and its detection: history-taking and the diagnostic phase of management. JADA 2001;132(11 suppl):12S–18S.[Abstract/Free Full Text]
  • Pelucchi C, Gallus S, Garavello W, Bosetti C, La Vecchia C. Cancer risk associated with alcohol and tobacco use: focus on upper aero-digestive tract and liver. Alcohol Res Health 2006;29(3):193–198.[Medline]
  • Centers for Disease Control and Prevention. Alcohol: frequently asked questions. Atlanta: Centers for Disease Control and Prevention; 2008. “www.cdc.gov/alcohol/faqs.htm#10“. Accessed March 10, 2010.
  • Shaha AR, Hoover EL, Mitrani M, Marti JR, Krespi YP. Synchronicity, multicentricity, and metachronicity of head and neck cancer. Head Neck Surg 1988;10(4):225–228.[Medline]
  • Panosetti E, Luboinski B, Mamelle G, Richard JM. Multiple synchronous and metachronous cancers of the upper aerodigestive tract: a nine-year study. Laryngoscope 1989;99(12):1267–1273.[Medline]
  • Erkal HS, Mendenhall WM, Amdur RJ, Villaret DB, Stringer SP. Synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites. J Clin Oncol 2001;19(5):1358–1362.[Abstract/Free Full Text]
  • Jansisyanont P, Pazoki A, Ord RA. Squamous cell carcinoma of the tongue after bone marrow transplantation in a patient with Fanconi’s anemia. J Oral Maxillofac Surg 2000;58(12):1454–1457.[Medline]
  • Alter BP, Giri N, Savage SA, Rosenberg PS. Cancer in dyskeratosis congenita. Blood 2009;113(26):6549–6557.[Abstract/Free Full Text]
  • Vinarsky V, Fine RL, Assaad A, et al. Head and neck squamous cell carcinoma in FAMMM syndrome. Head Neck 2009;31(11):1524–1527.[Medline]
  • Thomson PJ. Field change and oral cancer: new evidence for widespread carcinogenesis? Int J Oral Maxillofac Surg 2002;31(3):262–266.[Medline]
  • Zila Pharmaceuticals. How VizilitePlus Works. “www.vizilite.com/about/“. Accessed April 5, 2010.
  • Huber MA, Bsoul SA, Terezhalmy GT. Acetic acid wash and chemiluminescent illumination as an adjunct to conventional oral soft tissue examination for the detection of dysplasia: a pilot study. Quintessence Int 2004;35(5):378–384.[Medline]
  • Orascoptic, a Kerr Company. Three in One Diagnostic Kit. “www.orascoptic.com/index/orascoptic-products-diagnostic-orascopticdk-2“. Accessed April 5, 2010.
  • AdDent. MicroLux Diagnostic System. “www.addent.com/docs/MicroluxDiagnosticSystemIllustrationsandText-Nov09.pdf“. Accessed April 5, 2010.
  • Velscope. Fluorescence Visualization Technology. “www.velscope.com/pdf/guides/LED%200101%20VELscope%20Single-sheet%20Product%20Brochure%20(N.A.)_G.pdf“. Accessed April 5, 2010.
  • Trimira. How it Works: Identafi 3000 Ultra Multispectral Oral Cancer Screening. “www.trimira.net/identafi“. Accessed April 5, 2010.
  • OralCDx BrushTest. Test with Confidence. “www.sopreventable.com/What2Test.htm“. Accessed April 5, 2010.
  • OralCDx BrushTest. How to Do the BrushTest “www.sopreventable.com/How2Use.htm“. Accessed April 5, 2010.
  • Patton LL, Epstein JB, Kerr AR. Adjunctive techniques for oral cancer examination and lesion diagnosis: a systematic review of the literature. JADA 2008;139(7):896–905.[Abstract/Free Full Text]
  • Speight PM, Palmer S, Moles DR, et al. The cost-effectiveness of screening for oral cancer in primary care. Health Technol Assess 2006; 10(14):1–144, iii–iv.[Medline]
  • Patton LL. The effectiveness of community-based visual screening and utility of adjunctive diagnostic aids in the early detection of oral cancer. Oral Oncol 2003;39(7):708–723.[Medline]
  • Kujan O, Glenny AM, Oliver RJ, Thakker N, Sloan P. Screening programmes for the early detection and prevention of oral cancer. Cochrane Database Syst Rev 2006;3:CD004150.[Medline]
  • Rosenberg D, Cretin S. Use of meta-analysis to evaluate tolonium chloride in oral cancer screening. Oral Surg Oral Med Oral Pathol 1989;67(5):621–627.[Medline]
  • Gupta A, Singh M, Ibrahim R, Mehrotra R. Utility of toluidine blue staining and brush biopsy in precancerous and cancerous oral lesions. Acta Cytol 2007;51(5):788–794.[Medline]
  • Rosen IB, Cornish M, Edelson J. Detection of early oral cancer by toluidine blue. J Can Dent Assoc (Tor) 1971;37(9):347–349.[Medline]
  • Santana JC, Delgado L, Miranda J, Sánchez M. Oral Cancer Case Finding Program (OCCFP). Oral Oncol 1997;33(1):10–12.[Medline]
  • Mehrotra R, Singh M, Thomas S, et al. A cross-sectional study evaluating chemiluminescence and autofluorescence in the detection of clinically innocuous precancerous and cancerous oral lesions. JADA 2010;141(2):151–156.[Abstract/Free Full Text]
  • U.S. Department of Health and Human Services. Procedure Manual, U.S. Preventive Services Task Force. “www.ahrq.gov/clinic/uspstf08/methods/procmanual.htm“. Accessed April 5, 2010.
  • Shekelle PG, Woolf SH, Eccles M, Grimshaw J. Clinical guidelines: developing guidelines. BMJ 1999;318(7183):593–596.[Free Full Text]
  • Napier SS, Speight PM. Natural history of potentially malignant oral lesions and conditions: an overview of the literature. J Oral Pathol Med 2008;37(1):1–10.[Medline]
  • Kujan O, Oliver RJ, Khattab A, Roberts SA, Thakker N, Sloan P. Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation. Oral Oncol 2006;42(10): 987–993.[Medline]
  • Mehanna HM, Rattay T, Smith J, McConkey CC. Treatment and follow-up of oral dysplasia: a systematic review and meta-analysis. Head Neck 2009;31(12):1600–1609.[Medline]
  • Sankaranarayanan R, Ramadas K, Thomas G, et al; Trivandrum Oral Cancer Screening Group. Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial. Lancet 2005;365(9475):1927–1933.[Medline]
  • Subramanian S, Sankaranarayanan R, Bapat B, et al. Cost-effectiveness of oral cancer screening: results from a cluster randomized controlled trial in India. Bull World Health Organ 2009;87(3):200–206.[Medline]
  • Melrose RJ, Handlers JP, Kerpel S, Summerlin DJ, Tomich CJ; American Academy of Oral and Maxillofacial Pathology. The use of biopsy in dental practice: the position of the American Academy of Oral and Maxillofacial Pathology. Gen Dent 2007;55(5):457–461.[Medline]
  • Speight PM, Zakrzewska J, Downer MC. Screening for oral cancer and precancer. Eur J Cancer B Oral Oncol 1992;28B(1):45–48.
  • Ram S, Siar CH. Chemiluminescence as a diagnostic aid in the detection of oral cancer and potentially malignant epithelial lesions. Int J Oral Maxillofac Surg 2005;34(5):521–527.[Medline]
  • Epstein JB, Silverman S Jr, Epstein JD, Lonky SA, Bride MA. Analysis of oral lesion biopsies identified and evaluated by visual examination, chemiluminescence and toluidine blue. Oral Oncol 2008; 44(6):538–544.[Medline]
  • Poh CF, Zhang L, Anderson DW, et al. Fluorescence visualization detection of field alterations in tumor margins of oral cancer patients. Clin Cancer Res 2006;12(22):6716–6722.[Abstract/Free Full Text]
  • Lane PM, Gilhuly T, Whitehead P, et al. Simple device for the direct visualization of oral-cavity tissue fluorescence. J Biomed Opt 2006;11(2):024006.[Medline]
  • Kerr AR, Sirois DA, Epstein JB. Clinical evaluation of chemiluminescent lighting: an adjunct for oral mucosal examinations. J Clin Dent 2006;17(3):59–63.[Medline]
  • Epstein JB, Gorsky M, Lonky S, Silverman S Jr., Epstein JD, Bride M. The efficacy of oral lumenoscopy (ViziLite) in visualizing oral mucosal lesions. Spec Care Dentist 2006;26(4):171–174.[Medline]
  • Lingen MW, Kalmar JR, Karrison T, Speight PM. Critical evaluation of diagnostic aids for the detection of oral cancer. Oral Oncol 2008;44(1):10–22.[Medline]