|Ahead of print publication
Efficacy of oral brush biopsy in the early detection of oral cancer and oral potentially malignant disorders - a systematic review
Department of Diagnostic Oral Sciences, Riyadh Elm University, Riyadh, Saudi Arabia
|Date of Submission||28-Feb-2021|
|Date of Decision||07-Sep-2021|
|Date of Acceptance||05-Nov-2021|
|Date of Web Publication||08-Jan-2022|
Department of Diagnostic Oral Sciences, Riyadh Elm University, P.O. Box: 84891, Riyadh: 11681
Source of Support: None, Conflict of Interest: None
Introduction: Oral cancer is one of the most prevalent cancers in South East Asian countries due to increased consumption of tobacco products and alcohol and ranks sixth among the malignancies worldwide. Several screening modalities such as toluidine blue, Lugol's iodine staining, exfoliative cytology, and biopsy are being used to detect suspicious oral potentially malignant disorders (PMDs) at an early stage. Oral brush biopsy is a painless and less invasive technique that uses variations of a small brush to collect cells from all three layers of epithelium. The technique is non-invasive and promises to be an adjunct to the gold-standard histopathological examination and diagnosis of oral PMD.
Aim: The aim of this systematic review was to compile studies pertaining to diagnostic utility of oral brush biopsy with or without computer-assisted cytological analysis in the screening of innocuous oral PMDs for early detection of cancerous changes.
Materials and Methods: Computerized literature search was performed to select eligible articles from the following databases: PubMed (MEDLINE), GOOGLE SCHOLAR, and SCIENCE DIRECT using specific keywords. The search was limited to articles published as full text in English, which were screened by two reviewers for eligibility.
Results and Discussion: Six studies satisfied our inclusion criteria and found oral brush biopsy as a moderately reliable screening tool for early detection of dysplastic changes in oral PMDs. For oral brush biopsy, sensitivity and specificity obtained were 97.7% and 84.5%, respectively, in the detection of high-grade dysplasia.
Conclusion: Brush cytology using a cytobrush is a reliable adjunct to histopathology in detecting oral premalignant and malignant oral lesions. Specificity and sensitivity of the technique requires further investigative clinical studies.
Keywords: Biopsy, brush, diagnosis, oral cancer, oral CDx®, potentially malignant disorders
|How to cite this URL:|
Shenoy M. Efficacy of oral brush biopsy in the early detection of oral cancer and oral potentially malignant disorders - a systematic review. Saudi J Oral Sci [Epub ahead of print] [cited 2022 Jan 23]. Available from: https://www.saudijos.org/preprintarticle.asp?id=335314
| Introduction|| |
Oral cancer is a major economic and clinical burden for the developing countries and ranks sixth to eighth among malignancies worldwide. In India, oral cancer accounts for 40% of all cancers and is more commonly in males due to habitual use of tobacco products and alcohol consumption which are the known evidence-based contributing factors for cancer development and progression. Several oral potentially malignant disorders (OPMDs) such as leukoplakia, oral submucous fibrosis, erythroplakia, and oral lichen planus have the potential to transform into malignancy. Among this prevalence of leukoplakia has been reported to be 2.6%, with a high rate of malignant transformation that varies between 1.36 and 2.9%. Prognosis is further complicated by the high rate of second primary tumors in these patients, which is thought to be the result of “field cancerization” in the upper aerodigestive tract. Early detection of neoplastic changes in the oral cavity is the best method to improve patient survival rates. A current method of clinical oral cancer diagnosis based on visual examination of the oral cavity relies heavily on clinical expertise in recognizing early neoplastic changes. However, discerning premalignant and early malignant lesions from common benign inflammatory conditions by visual examination is difficult, even for experienced practitioners.
Early detection of suspicious precancerous lesions and conditions could be done by various diagnostic methods such as exfoliative cytology, brush biopsy, incisional, and excisional biopsy. Computer-assisted transepithelial sample analysis known as Oral CDx® brush biopsy is a minimally invasive painless technique that uses specially designed small cytobrush to collect cells of all epithelial layers and serve as a promising substitute to invasive scalpel biopsies. Published literature reviews on this technique applied to oral PMDs are not many. The rationale behind this review was to evaluate the diagnostic efficacy of oral brush biopsy as an adjunct to the gold standard of histopathological diagnosis for early detection of dysplastic changes in oral PMDs and to reduce the risk of malignant transformation. The aim of this systematic review was to evaluate the published literature on the diagnostic efficacy of oral brush biopsy and subsequent computer-assisted analysis CDx® in oral cancer detection.
| Materials and Methods|| |
Literature search strategy
A systematic review of the scientific literature was done on the topic. The electronic retrieval systems and databases searched for relevant articles were PubMed (MEDLINE), GOOGLE SCHOLAR, and SCIENCE DIRECT. Database of indexed journals was searched using keywords such as oral cancer, histopathological diagnosis, PMDs, brush biopsy, and oral CDx®. The inclusion criteria were the use of oral brush biopsy with and without computer-assisted analysis for early diagnosis of OSCC or OPMDs and English language publications reporting primary studies (The exclusion criteria were case reports, reviews, and studies in other languages.).
[Figure 1] shows that the initial computerized search strategy yielded 406 titles. In the first selection two reviewers with 10 years' experience in the field, screened the articles by reading titles and abstracts of the retrieved publications and 326 were discarded because these articles did not fulfill the inclusion criteria. Any conflicting views were resolved by mutual discussion between reviewers. Out of those 326 articles, 202 were excluded as these were case reports, review articles, and in vitro studies. The remaining 80 articles that fulfilled the eligibility criteria were read in full. Among these 80 articles, 74 were excluded due to lack of adequate data and discrepancy in outcome, leaving only 6 studies that met our inclusion criteria. Later, each reviewer performed screening of eligible articles individually and obtained the full text of final eligible studies for the systematic review.
On the basis of studies characteristics of title of the paper, authors' information, year of study, geographical location, characteristics of the participants, aim and objectives, study design, results and statistical analysis, results, conclusion, and references cited, two reviewers independently extracted data using the standard data extraction designed form. Studies focusing on the diagnostic efficacy of oral brush biopsy as a screening method for oral cancer detection were analyzed for bias by the reviewers. Differences between the reviewers were resolved by mutual discussion. [Table 1] describes the characteristics of the included studies.
| Results|| |
All the six studies found oral brush biopsy as a reliable screening tool for early detection of dysplastic changes in oral PMDs and confirmation of definitive diagnosis by incisional/excisional biopsy as essential.
[Table 2] summarizes the design and results of the six eligible studies on the diagnostic utility of oral brush biopsy with or without computer-assisted cytological analysis in screening of oral cancer.,,,,, Reddy et al. found sensitivity of oral brush biopsy at 43.5% and a specificity of 81.25% with a positive predictive value of 58.3% for 60 patients with clinically diagnosed oral leukoplakia. In another study by Trakroo et al. cytopathological and histopathological scores of premalignant and malignant lesions were compared for 50 patients with premalignant lesions and conditions, P < 0.05 which was statistically significant. Both studies suggested that oral brush biopsy is a promising adjunct to definitive histopathological diagnosis of oral PMDs and oral cancer at an early stage. Swati et al. found that modified oral brush biopsy had higher specificity (68.42%) and sensitivity (81.69%) than exfoliative cytology with specificity of 86.48% and sensitivity of 48.57% making it a reliable screening tool for patients with oral precancerous lesions. Velleuer et al. found diagnostic effectiveness of oral brush biopsy in the detection of high-grade oral epithelial dysplasia in 30 patients with clinical visible oral lesions, and sensitivity and specificity obtained were 97.7% and 84.5%, respectively.
|Table 2: Summary of diagnostic utility of oral brush biopsy with or without computer assisted cytological analysis in screening of oral cancer|
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[Table 3] shows data on the diagnostic accuracy of included studies for oral brush biopsy in the detection of oral PMDs and oral cancer. Write something short about the data !!! Study by Trakroo et al., showed less number of references cited with positive likelihood of 93.10%.
Based on the analysis of data from six studies, oral brush biopsy appears an accurate test in identifying suspicious oral premalignant and malignant lesions, even if minimally suspicious. Very limited studies have been conducted in literature in this domain, and to this consideration future investigatory studies should be performed to validate the diagnostic utility of oral brush biopsy in comparison to other chair-side diagnostic aids in early detection of oral cancer.
Risk of Bias Assessment across individual studies
[Table 4] shows that all studies demonstrated low-risk bias using COCHRANE BIAS TOOL.,,,,, All studies showed low-risk bias for randomization whereas high-risk bias was found for allocation concealment and blinding of participants. No inadequacy towards outcome data was observed for all studies.
| Discussion|| |
Dental clinicians encounter various oral mucosal lesions in routine practice that may present as diagnostic dilemmas. Suspicious oral lesions require scalpel biopsy, incisional or excisional to rule out mild, moderate, and severe dysplasia. Lesions with moderate or severe dysplasia should be referred to cancer specialist; however, it is difficult to perform invasive initial biopsy as a screening tool for detection of dysplasia in all suspected oral PMDs. To the above consideration, adjunctive chair-side diagnostic aids that include toluidine blue and Lugol's iodine vital staining, exfoliative and oral brush cytology, and light-based detection systems, have been used with variable success rates.
Oral brush biopsy is a painless, minimally invasive technique that uses specially designed brush to obtain transepithelial specimen and has been found to have higher diagnostic accuracy than exfoliative cytology in early detection of oral cancer. Moreover, it serves as a non-invasive substitute to scalpel biopsy to rule out dysplasia in patients with suspicious oral lesions. Recently computer-based cytological analysis, oralCDx® brush biopsy is becoming popular for obtaining transepithelial samples that are subsequently analyzed using an image analysis system. Several studies have reported high sensitivity and specificity of oralCDx® in the detection of dysplasia in oral PMDs when compared to scalpel biopsy.,,,,,
In this context, oral brush biopsy was used in six eligible studies based on the inclusion and exclusion criteria that suggested it to be a reliable diagnostic test in the detection of oral cancer at an early stage. Parameters to be analyzed in the smear (brush biopsy samples) include enlarged nuclei, nuclear pleomorphism, nucleocytoplasmic ratio, number of nuclei, binucleation, keratinization, hyperchromatism, mitotic figures, and discrepancy in nuclear cytoplasmic ratio. Based on these, a classification was proposed for cytological analysis as follows: class 0; inadequate specimen, class 1; no abnormal or atypical cells, class 2; Atypical cells but no evidence of malignancy, class 3; cytology suggestive of, but not conclusive for malignancy, class 4; strongly suggestive for malignancy, class 5; conclusive for malignancy. Among these, classes 3 to 5 were considered positive whereas class 1 and 2 as negative.
On analysis of diagnostic accuracy of studies, Velleuer et al. found sensitivity and specificity of oral brush biopsy as 97.7% and 84.5%, respectively in diagnosis of high-grade dysplasia associated with suspicious oral PMDs. Swati et al. found higher specificity (68.42%) and sensitivity (81.69%) of modified oral brush biopsy when compared to exfoliative cytology with specificity (86.48%) and sensitivity (48.57%). Trakroo et al. suggested it to be a useful and reliable diagnostic adjunct to microscopic analysis. They reported statistically significant differences between cytopathological and histopathological scores of premalignant and malignant lesions (P < 0.05).
Studies have documented higher diagnostic accuracy of oral brush biopsy than scalpel biopsy, however, in some cases, biopsy is mandatory especially if oral lesion exhibits clinical features of malignancy, such as a rapidly enlarging mass, chronic nonhealing ulceration, or presence of induration on palpation. Oral PMDs such as erosive or ulcerative oral lichen planus, non-homogeneous ulcerative leukoplakia, erythroplakia may exhibit surface ulceration or erythema, and scalpel biopsy should be done to arrive at an accurate diagnosis. Contrary to this, scalpel biopsy is invasive and is not recommended in medically compromised patients with hematological disorder, coronary artery disease, renal and hepatic impairment which necessitates consultation with a physician to prevent complications. In these situations, oral brush biopsy should be carried out due to its potential advantages of being painless, non-invasive technique, and assists the clinician in the detection of malignant changes at an early stage. Oral brush biopsy may be useful in patients with multiple oral lesions, where the patient refuses to give written informed consent. Studies included in this systematic review suggested oral brush biopsy as a promising screening modality for innocuous oral PMDs, however, further studies should be conducted to substantiate the findings.,,,,,
| Conclusion|| |
Oral brush biopsy can be a useful screening tool before the initiation of scalpel biopsy, and this procedure was found to be well accepted by the patients. However, in future studies using deoxyribonucleic acid (DNA) flow cytometry should be conducted to enhance the appearance of lesions for early diagnosis of oral cancer and potentially malignant disorders.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]