Assignment 2C – Priscilla Kaljanac
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Evidence-informed decision-making
Oral Health Question
In adult clients, does the use of adjunctive diagnostic aids result in more accurate
detection of precancerous and cancerous oral lesions than conventional intra/extra oral
examination alone?
Introduction
While conventional oral examination (COE) may be useful, it does not identify all
potentially premalignant lesions. A variety of adjunctive techniques are available to
assist in the screening of healthy patients for cancer/precancer. This analysis critically
examines the literature associated with oral cancer screening adjuncts such as brush
biopsy, toluidine blue, chemilumescence, and fluorescence, to determine its efficacy in
primary care settings.
The studies were assessed according to the following criteria: Results should be
compared to the “gold standard,” histological scalpel biopsy and evaluation by an expert
in oral pathology. Studies should be randomized and blinded. The population should
represent general clinical practice (low-risk). The study should use primary care
examiners who are most likely to perform the screening in practice. The test should
distinguish cancer/precancer from other conditions, and lastly, the study should provide
sufficient detail about the sample, the test, and how it was analyzed and interpreted.
Brush Biopsy
A study by Svirsky et al.1 analyzed oral brush biopsy with scalpel biopsies. A major
strength of this study is that general dentists performed the initial examination and brush
biopsy. A major weakness of this study is that those with negative brush biopsies did
not receive a scalpel biopsy; therefore there was no comparison for these patients.
There is also insufficient information on sampled lesions, which may bias calculations of
sensitivity and specificity. The lack of control and documentation of sample selection
limits the utility of this study.
Christian2 investigated the utility of the brush biopsy by screening low-risk dentists and
dental hygienists at an ADA meeting. Participants with abnormal but asymptomatic oral
lesions underwent a brush biopsy, but of the seven lesions that were abnormal by brush
biopsy, only four had scalpel biopsy. Strengths of this study include a large sample size,
a low-risk study population, and evaluation of innocuous lesions (which this technology
is designed to identify) rather than visually suspicious lesions. However, this study also
fails to perform scalpel biopsies on all subjects, skewing calculation of sensitivity and
specificity.
Systematic reviews3,4 and Cochrane systematic reviews5,6 agree that oral brush biopsy
shows promise, but further quality studies need to be conducted. This should include
studies in primary care settings with subjects having innocuous lesions that are fully
controlled with scalpel biopsy.
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Toluidine Blue (TB)
A systematic review by Gray et al.7 identified 77 publications on TB. However, only 14 of
these evaluated TB’s ability to identify oral cancers that would not have been diagnosed
by COE. Most of the studies8,9,10 analyzed here and within systematic reviews3-7,11,12
were not RCTs, none were conducted in a primary care setting, and most studies were
case series conducted by specialists on high-risk populations, usually with known
suspicious lesions. Other problems with current studies3-11 are differing methods among
studies, and the rare use of scalpel biopsy as a gold standard.
Su et al.10 was the only RCT found. It showed significantly more (5%) premalignant
lesions than the control group, but was conducted on high-risk population (smoking,
betel nut chewing). A positive is that dentists in primary practice evaluated participants,
and results were compared to scalpel biopsy.
All studies8,9,10 and systematic reviews3-7,11,12 fail to show that toluidine blue is effective
as a screening test among low-risk individuals in a primary care setting. Until more
studies are conducted, especially among low-risk individuals, the high rate of false
positives and the low specificity in staining dysplasia likely outweigh the potential
benefits of detecting additional cancers.
Chemiluminescence
Chemiluminescence is another method intended to enhance the identification of oral
mucosal abnormalities. Ram and Sair13 examined 40 patients with a previous history of
oral cancer/premalignancy by chemiluminescence. Weaknesses are the small sample
size, lesions examined were suspicious not innocuous, and 1/3 of the lesions did not
undergo scalpel biopsy. Other recent multi-center chemiluminsence studies14,15 involving
patients with a history of previously-detected oral mucosal lesions reported significant
improvements in either the brightness, sharpness and texture did not significantly
improve lesion detection compared to COE. These studies did not compare findings to
scalpel biopsy.
Only Mehrotra et al.16 compared chemiluminescence screening results with histologic
findings in innocuous lesions from COE, but was unable to identify any lesions that were
not already apparent during COE.
Systematic reviews3-6,10,11 conclude that no current studies are able to demonstrate that
chemiluminescence helps in differentiating cancerous/precancerous lesions from benign
lesions. This is because the published studies suffer from numerous experimental
design issues, especially failing to compare to scalpel biopsy.
Fluorescence
Lane et al.17 studied 44 patients who had a history of cancer/precancer with
fluorescence and COE. Scalpel biopsies were also obtained. Fluorescence
demonstrated 98% sensitivity and 100% specificity for discriminating cancer/precancer
from normal mucosa. However, all cancer/precancer were also observed with COE.
Major strengths of this study: directly compared to scalpel biopsy, and the high degree of
sensitivity and specificity. The weaknesses: small sample size (n = 44), and the majority
of the lesions were the suspicious type.
Assignment 2C – Priscilla Kaljanac
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A case series study by Poh et al.18 demonstrated that fluorescence can identify lesions
that cannot be seen under COE. This is a major improvement in oral cancer screening.
Strength is that all three lesions appear to be innocuous. A major weakness is that rather
than an RCT, the study is anecdotal observations from individual cases.
While results are promising, information on fluorescence to identify
premalignancy/malignancy in innocuous lesions or to reveal lesions undetectable under
COE is limited, and requires additional well-designed clinical trials screening lower-risk
populations (without a history of cancer/precancer) and in patients seen by primary care
providers.
Conclusion
None of the studies were able to establish the utility of adjunctive techniques in primary
care settings for use by primary practitioners. They could not determine whether they
result in increased visualisation or identification of oral cancer in primary care settings.
However there may be use for these adjunctive techniques in secondary settings to
improve visualisation and detection. For these reasons, more multi-centre studies that
examine the utility of adjunctive techniques for use by non-specialists in primary care
settings are needed.
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References
1. Svirsky JA, Burns JC, Carpenter WM, Cohen DM, Bhattacharyya, JE, Fantasia JE, et
al. Comparison of computer-assisted brush biopsy results with follow up scalpel
biopsy and histology. Gen Dent 2002;50(6):500–3.
2. Christian DC. Computer-assisted analysis of oral brush biopsies at an oral cancer
screening program. J Am Dent Assoc 2002;133(3):357-62.
3. Lingen MW, Kalmar JR, Karrison T, Speight PM. Critical evaluation of diagnostic aids
for the detection of oral cancer. Oral Oncol. 2008 Jan;44(1):10-22.
4. Patton LL, Epstein JB, Kerr AR. Adjunctive techniques for oral cancer examination
and lesion diagnosis: A systematic review of the literature. Am Dent Assoc
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5. Brocklehurst P, Kujan O, Glenny AM, Oliver R, Sloan P, Ogden G, Shepherd S.
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7. Gray M, Gold L, Burls A, Elley K. The clinical effectiveness of toluidine blue dye as an
adjunct to oral cancer screening in general dental practice: A west midlands
development and evaluation service report. Birmingham, England: Development
and Evaluation Service, Department of Public Health and Epidemiology,
University of Birmingham; 2000. Avalable from:
www.rep.bham.ac.uk/2000/toludine_blue.pdf” Accessed April 5, 2011.
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12. Fedele S. Diagnostic aids in the screening of oral cancer. Head Neck Oncol. 2009
Jan 30;1:5.
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13. 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
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14. Epstein JB, Gorsky M, Lonky S, Silverman Jr S, Epstein JD, Bride M. The efficacy of
oral lumenoscopy (ViziLite) in visualizing oral mucosal lesions. Spec Care Dent
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15. 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.
16. Mehrotra R, Singh M, Thomas S, Nair P, Pandya S, Nigam NS, Shukla P. A crosssectional study evaluating chemiluminescence and autofluorescence in the
detection of clinically innocuous precancerous and cancerous oral lesions. J Am
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17. Lane PM, Gilhuly T, Whitehead P, Zeng H, Poh CF, Ng S, et al. Simple device for
the direct visualization of oral-cavity tissue fluorescence. J Biomed Opt
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18. Poh CF, Williams PM, Zhang L, Laronde DM, Lane P, MacAulay C, et al. Direct
fluorescence visualization of clinically occult highrisk oral premalignant disease
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