Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Jul 20;7(7):CD010276.
doi: 10.1002/14651858.CD010276.pub3.

Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions

Tanya Walsh  1 , Richard Macey  1 , Alexander R Kerr  2 , Mark W Lingen  3 , Graham R Ogden  4 , Saman Warnakulasuriya  5
Affiliations
Meta-Analysis

Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions

Tanya Walsh et al. Cochrane Database Syst Rev. .

Abstract

Background: Squamous cell carcinoma is the most common form of malignancy of the oral cavity, and is often proceeded by oral potentially malignant disorders (OPMD). Early detection of oral cavity squamous cell carcinoma (oral cancer) can improve survival rates. The current diagnostic standard of surgical biopsy with histology is painful for patients and involves a delay in order to process the tissue and render a histological diagnosis; other diagnostic tests are available that are less invasive and some are able to provide immediate results. This is an update of a Cochrane Review first published in 2015.

Objectives: Primary objective: to estimate the diagnostic accuracy of index tests for the detection of oral cancer and OPMD, in people presenting with clinically evident suspicious and innocuous lesions.

Secondary objective: to estimate the relative accuracy of the different index tests.

Search methods: Cochrane Oral Health's Information Specialist searched the following databases: MEDLINE Ovid (1946 to 20 October 2020), and Embase Ovid (1980 to 20 October 2020). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were also searched for ongoing trials to 20 October 2020. No restrictions were placed on the language or date of publication when searching the electronic databases. We conducted citation searches, and screened reference lists of included studies for additional references.

Selection criteria: We selected studies that reported the diagnostic test accuracy of the following index tests when used as an adjunct to conventional oral examination in detecting OPMD or oral cavity squamous cell carcinoma: vital staining (a dye to stain oral mucosa tissues), oral cytology, light-based detection and oral spectroscopy, blood or saliva analysis (which test for the presence of biomarkers in blood or saliva).

Data collection and analysis: Two review authors independently screened titles and abstracts for relevance. Eligibility, data extraction and quality assessment were carried out by at least two authors, independently and in duplicate. Studies were assessed for methodological quality using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Meta-analysis was used to combine the results of studies for each index test using the bivariate approach to estimate the expected values of sensitivity and specificity.

Main results: This update included 63 studies (79 datasets) published between 1980 and 2020 evaluating 7942 lesions for the quantitative meta-analysis. These studies evaluated the diagnostic accuracy of conventional oral examination with: vital staining (22 datasets), oral cytology (24 datasets), light-based detection or oral spectroscopy (24 datasets). Nine datasets assessed two combined index tests. There were no eligible diagnostic accuracy studies evaluating blood or salivary sample analysis. Two studies were classed as being at low risk of bias across all domains, and 33 studies were at low concern for applicability across the three domains, where patient selection, the index test, and the reference standard used were generalisable across the population attending secondary care. The summary estimates obtained from the meta-analysis were: - vital staining: sensitivity 0.86 (95% confidence interval (CI) 0.79 to 0.90) specificity 0.68 (95% CI 0.58 to 0.77), 20 studies, sensitivity low-certainty evidence, specificity very low-certainty evidence; - oral cytology: sensitivity 0.90 (95% CI 0.82 to 0.94) specificity 0.94 (95% CI 0.88 to 0.97), 20 studies, sensitivity moderate-certainty evidence, specificity moderate-certainty evidence; - light-based: sensitivity 0.87 (95% CI 0.78 to 0.93) specificity 0.50 (95% CI 0.32 to 0.68), 23 studies, sensitivity low-certainty evidence, specificity very low-certainty evidence; and - combined tests: sensitivity 0.78 (95% CI 0.45 to 0.94) specificity 0.71 (95% CI 0.53 to 0.84), 9 studies, sensitivity very low-certainty evidence, specificity very low-certainty evidence.

Authors' conclusions: At present none of the adjunctive tests can be recommended as a replacement for the currently used standard of a surgical biopsy and histological assessment. Given the relatively high values of the summary estimates of sensitivity and specificity for oral cytology, this would appear to offer the most potential. Combined adjunctive tests involving cytology warrant further investigation. Potentially eligible studies of blood and salivary biomarkers were excluded from the review as they were of a case-control design and therefore ineligible. In the absence of substantial improvement in the tests evaluated in this updated review, further research into biomarkers may be warranted.

PubMed Disclaimer

Conflict of interest statement

Tanya Walsh: none known. I am Statistical Editor for Cochrane Oral Health. Richard Macey: none known. Alexander R Kerr: none known. Mark Lingen: none known. Graham Ogden: none known. Saman Warnakulasuriya: none known. I was a co‐author on three of the included studies but was not involved in selecting or assessing them.

Figures

1
1
Study flow diagram.
2
2
Risk of bias and applicability concerns graph: review authors' judgements about each domain presented as percentages across included studies.
3
3
Risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study.
4
4
Forest plot of tests: cytology, light‐based, vital staining, combined tests that included 63 studies (79 datasets) evaluating 7942 lesions (TP: true positives, FP: false posititves, FN: false negatives, TN: true negatives).
5
5
Summary receiver operating characteristic (SROC) plot of tests: cytology, light‐based, vital staining, and combined tests.
6
6
Summary receiver operating characteristic (SROC) plot of cytology grouped by different techniques.
7
7
Summary receiver operating characteristic (SROC) plot of light‐based index tests grouped by different techniques.
1
1. Test
All
2
2. Test
Vital staining with application method covariate
3
3. Test
Cytology with covariate
4
4. Test
Light‐based with covariate
6
6. Test
Vital staining plus adjunct (light or cytology)
See this image and copyright information in PMC

Update of

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Adil 2017 {published data only}
    1. Adil HA, Yuwanati M, Singh A, Sawant S, Umarji HR. Comparative study on the efficacy of tissue autofluorescence (Visually Enhanced Lesion scope) and toluidine blue as a screening method in oral potentially malignant and malignant lesions. Journal of Medical Sciences (Taiwan) 2017;37(3):91-6.
Allegra 2009 {published data only}
    1. Allegra E, Lombardo N, Puzzo L, Garozzo A. The usefulness of toluidine staining as a diagnostic tool for precancerous and cancerous oropharyngeal and oral cavity lesions [Utilità della colorazione con toluidina nella diagnosi delle lesioni precancerosee cancerose dell’orofaringe e del cavo orale]. ACTA Otorhinolaryngologica Italica 2009;29:187-90. - PMC - PubMed
Amirchaghmaghi 2018 {published data only}
    1. Amirchaghmaghi M, Mohtasham N, Delavarian Z, Shakeri MT, Hatami M, Mosannen Mozafari P. The diagnostic value of the native fluorescence visualization device for early detection of premalignant/malignant lesions of the oral cavity. Photodiagnosis and Photodynamic Therapy 2018;21:19-27. - PubMed
Awan 2011 {published data only}
    1. Awan KH, Morgan PR, Warnakulasuriya S. Evaluation of an autofluorescence based imaging system (VELscope™) in the detection of oral potentially malignant disorders and benign keratoses. Oral Oncology 2011;47:274-7. - PubMed
    1. Awan KH, Morgan PR, Warnakulasuriya S. Utility of chemiluminescence (ViziLite) in the detection of oral potentially malignant disorders and benign keratoses. Journal of Oral Pathology & Medicine 2011;40(7):541-4. - PubMed
Awan 2012 {published data only}
    1. Awan KH, Yang YH, Morgan PR, Warnakulasuriya S. Utility of toluidine blue as a diagnostic adjunct in the detection of potentially malignant disorders of the oral cavity – a clinical and histological assessment. Oral Diseases 2012;18:728-33. - PubMed
Baeten 2018 {published data only}
    1. Baeten J, Johnson A, Sunny S, Suresh A, Birur P, Uma K, et al. Chairside molecular imaging of aberrant glycosylation in subjects with suspicious oral lesions using fluorescently labeled wheat germ agglutinin. Head & Neck 2018;40(2):292-301. - PubMed
Cancela‐Rodriguez 2011 {published data only}
    1. Cancela-Rodriguez P, Cerero-Lapiedra R, Esparza-Gomez G, Llamas-Martinez S, Warnakulasuriya S. The use of toluidine blue in the detection of premalignant and malignant oral lesions. Journal of Oral Pathology & Medicine 2010;40:300-4. - PubMed
Chainani‐Wu 2015 {published data only}
    1. Chainani-Wu N, Madden E, Cox D, Sroussi H, Epstein J, Silverman Jr S. Toluidine blue aids in detection of dysplasia and carcinoma in suspicious oral lesions. Oral Diseases 2015;21:879-85. - PubMed
Chaudhari 2013 {published data only}
    1. Chaudhari A, Hegde-Shetiya S, Shirahatti R, Agrawal D. Comparison of different screening methods in estimating the prevalence of precancer and cancer amongst male inmates of a jail in Maharashtra, India. Asian Pacific Journal of Cancer Prevention 2013;14(2):859-64. - PubMed
Chen 2007 {published data only}
    1. Chen Y-W, Lin J-S, Fong JH-J, Wang I-K, Chou S-J, Wu C-H, et al. Use of methylene blue as a diagnostic aid in early detection of oral cancer and precancerous lesions. British Journal of Oral and Maxillofacial Surgery 2007;45(7):590-1. - PubMed
Cheng 2003a {published data only}
    1. Cheng B, Yang L. The clinical evaluation of Oratest in detecting oral mucosal lesions. West China Journal of Stomatology 2003;21(2):124-6. - PubMed
Cheng 2003b {published data only}
    1. Cheng B, Yang L. The clinical evaluation of Oratest in detecting oral mucosal lesions. West China Journal of Stomatology 2003;21(2):124-6. - PubMed
Chiang 2019 {published data only}
    1. Chiang TE, Lin YC, Li YH, Wu CT, Kuo CS, Chen YW. Comparative evaluation of autofluorescence imaging and histopathological investigation for oral potentially malignant disorders in Taiwan. Clinical Oral Investigations 2019;23(5):2395-402. - PubMed
Delavarian 2010 {published data only}
    1. Delavarian Z, Mohtasham N, Mosannen-Mozaffari P, Pakfetrat A, Shakeri M-T, Ghafoorian-Maddah R. Evaluation of the diagnostic value of a Modified Liquid-Based Cytology using OralCDx Brush in early detection of oral potentially malignant lesions and oral cancer. Medicina Oral, Patologia Oral y Cirugia Bucal 2010;15(5):e671-6. - PubMed
Du 2007 {published data only}
    1. Du GF, Li CZ, Chen HZ, Chen XM, Xiao Q, Cao ZG, et al. Rose bengal staining in detection of oral precancerous and malignant lesions with colorimetric evaluation: a pilot study. International Journal of Cancer 2007;120(9):1958-63. - PubMed
Epstein 2008 {published data only}
    1. 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 Oncology 2008;44:538-44. - PubMed
Farah 2007 {published data only}
    1. Farah CS, McCullough MJ. A pilot case control study on the efficacy of acetic acid wash and chemiluminescent illumination (ViziLite) in the visualisation of oral mucosal white lesions. Oral Oncology 2007;43:820-4. - PubMed
Farah 2012 {published data only}
    1. Farah CS, McIntosh L, Georgiou A, McCullough MJ. Efficacy of tissue autofluorescence imaging (VELscope) in the visualization of oral mucosal lesions. Head & Neck 2012;32(6):856-62. - PubMed
Fontes 2013 {published data only}
    1. Fernandes da Costa Fontes KB, Cunha KSG, Rodrigues FR, da Silva LE, Dias EP. Concordance between cytopathology and incisional biopsy in the diagnosis of oral squamous cell carcinoma. Brazilian Oral Research 2013;27(2):122-7. - PubMed
Ganga 2017 {published data only}
    1. Ganga RS, Gundre D, Bansal S, Shirsat PM, Prasad P, Desai RS. Evaluation of the diagnostic efficacy and spectrum of autofluorescence of benign, dysplastic and malignant lesions of the oral cavity using VELscope. Oral Oncology 2017;75:67-74. - PubMed
Guneri 2011 {published data only}
    1. Guneri P, Epstein JB, Kaya A, Veral A, Kazandy A, Boyacioglu H. The utility of toluidine blue staining and brush cytology as adjuncts in clinical examination of suspicious oral mucosal lesions. Oral and Maxillofacial Surgery 2011;40:155-66. - PubMed
Gupta 2007 {published data only}
    1. Gupta A, Singh M, Ibrahim R, Mehrotra R. Utility of toluidine blue staining and brush biopsy in precancerous and cancerous oral lesions. Acta Cytologica 2007;51(5):788-94. - PubMed
Hanken 2013 {published data only}
    1. Hanken H, Kraatz J, Smeets R, Heiland M, Assaf AT, Blessmann M, et al. The detection of oral premalignant lesions with an autofluorescence based imaging system (VELscope™) - a single-blinded clinical evaluation. Head & Face Medicine 2013;9:23. - PMC - PubMed
Jayasinghe 2020 {published data only}
    1. Jayasinghe RD, Hettiarachchi PVKS, Amugoda D, Kumaraarachchi M, Liyanage RLPR, Siriwardena BSMS, et al. Validity of toluidine blue test as a diagnostic tool for high risk oral potentially malignant disorders - a multicentre study in Sri Lanka. Journal of Oral Biology and Craniofacial Research 2020;10(4):547-51. - PMC - PubMed
Johnson 2019 {published data only}
    1. Johnson A, Baeten J, Patel K, Killian M, Sunny S, Suresh A, et al. Evaluation of a lectin-based imaging system for the chairside detection of oral dysplasia and malignancy. Journal of Oral and Maxillofacial Surgery 2019;77(9):1941-51. - PubMed
Kämmerer 2013 {published data only}
    1. Kämmerer PW, Koch FP, Santoro M, Babaryka G, Biesterfeld S, Brieger J, et al. Prospective, blinded comparison of cytology and DNA-image cytometry of brush biopsies for early detection of oral malignancy. Oral Oncology 2013;49(5):420-6. - PubMed
Kaur 2016 {published data only}
    1. Kaur M, Handa U, Mohan H, Dass A. Evaluation of brush cytology and DNA image cytometry for the detection of cancer of the oral cavity. Diagnostic Cytopathology 2016;44(3):201-5. - PubMed
Koch 2011a {published data only}
    1. Koch FP, Kunkel M, Biesterfeld S. Diagnostic efficiency of differentiating small cancerous and precancerous lesions using mucosal brush smears of the oral cavity - a prospective and blinded study. Clinical Oral Investigations 2011;15:763-9. - PubMed
Koch 2011b {published data only}
    1. Koch FP, Kaemmerer PW. Effectiveness of autofluorescence to identify suspicious oral lesions - a prospective, blinded clinical trial. Clinical Oral Investigations 2011;15:975-82. - PubMed
Leunig 2000 {published data only}
    1. Leunig A, Betz CS, Mehlmann M, Stepp H, Arbogast S, Grevers G, et al. Detection of squamous cell carcinoma of the oral cavity by imaging 5-aminolevulinic acid-induced protoporphyrin IX fluorescence. Laryngoscope 2000;110(1):78-83. - PubMed
Liu 2019 {published data only}
    1. Liu Y, Gao Y, Chen XJ, Hua H. DNA cytometry of exfoliated cells in the diagnosis of oral potential malignant disorders. Beijing Da Xue Xue Bao [Journal of Peking University. Health Sciences] 2019;51(1):16-20. - PMC - PubMed
Ma 2014 {published data only}
    1. Ma J-M, Zhou T-J, Wang R, Shan J, Wu Y-N, Song X-L, et al. Brush biopsy with DNA-image cytometry: a useful and non-invasive method for monitoring malignant transformation of potentially malignant oral disorders. European Archives of Oto-rhino-laryngology 2014;271(12):3291-5. - PubMed
Mashberg 1980 {published data only}
    1. Mashberg A. Re-evaluation of toluidine blue application as a diagnostic adjunct in the detection of asymptomatic oral squamous carcinoma: a continuing prospective study of oral cancer Ill. American Cancer Society 1980;4:758-63. - PubMed
McIntosh 2009 {published data only}
    1. McIntosh L, McCullough MJ, Farah CS. The assessment of diffused light illumination and acetic acid rinse (Microlux/DL) in the visualisation of oral mucosal lesions. Oral Oncology 2009;45:e227-31. - PubMed
Mehrotra 2008 {published data only}
    1. Mehrotra R, Kumar Singh M, Pandya S, Singh M. The use of an oral brush biopsy without computer-assisted analysis in the evaluation of oral lesions: a study of 94 patients. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 2008;106:246-53. - PubMed
Mehrotra 2010 {published data only}
    1. Mehrotra R, Singh M, Thomas S, Nair P, Pandya S, Shakti Nigam N, et al. A cross-sectional study evaluating chemiluminescence and autofluorescence in the detection of clinically innocuous precancerous and cancerous oral lesions. Journal of the American Dental Association 2010;141:151-6. - PubMed
Mehrotra 2011 {published data only}
    1. Mehrotra R, Mishra S, Singh M, Singh M. The efficacy of oral brush biopsy with computer assisted analysis in identifying precancerous and cancerous lesions. Head & Neck Oncology 2011;3(39):1-7. - PMC - PubMed
Mojsa 2012 {published data only}
    1. Mojsa I, Kaczmarzyk T, Zaleska M, Stypulkowska J, Zapala-Pospiech A, Sadecki D. Value of the ViziLite Plus System as a diagnostic aid in the early detection of oral cancer/premalignant epithelial lesions. Journal of Craniofacial Surgery 2012;23(2):162-4. - PubMed
Nagaraju 2010 {published data only}
    1. Nagaraju K, Prasad S, Ashok L. Diagnostic efficiency of toluidine blue with Lugol's iodine in oral premalignant and malignant lesions. Indian Journal of Dental Research 2010;21(2):218-23. - PubMed
Nanayakkara 2016 {published data only}
    1. Nanayakkara PG, Dissanayaka WL, Nanayakkara BG, Amaratunga EA, Tilakaratne WM. Comparison of spatula and cytobrush cytological techniques in early detection of oral malignant and premalignant lesions: a prospective and blinded study. Journal of Oral Pathology & Medicine 2016;45(4):268-74. - PubMed
Navone 2004 {published data only}
    1. Navone R, Marsico A, Reale I, Pich A, Broccoletti R, Pentenero M, et al. Usefulness of oral cytology for the diagnosis of oral squamous dysplasia and carcinoma. Minerva Stomatologica 2003;53(3):77-86. - PubMed
Navone 2008 {published data only}
    1. Navone R, Pentenero M, Rostan I, Burlo P, Marsico A, Broccoletti R, et al. Oral potentially malignant lesions: first-level micro-histological diagnosis from tissue fragments sampled in liquid-based diagnostic cytology. Journal of Oral Pathology & Medicine 2008;37:358-63. - PubMed
Ng 2012 {published data only}
    1. Ng SP, Mann IS, Zed C, Doudkine A, Matisic J. The use of quantitative cytology in identifying high-risk oral lesions in community practice. Oral and Maxillofacial Pathology 2012;114(3):358-64. - PubMed
Onizawa 1999 {published data only}
    1. Onizawa K, Saginoya H, Furuya Y, Yoshida H, Fukuda H. Usefulness of fluorescence photography for diagnosis of oral cancer. Oral and Maxillofacial Surgery 1999;28:206-10. - PubMed
Onofre 2001 {published data only}
    1. Onofre MA, Sposto MR, Navarro CM. Reliability of toluidine blue application in the detection of oral epithelial dysplasia and in situ and invasive squamous cell carcinomas. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 2001;91(5):535-40. - PubMed
Petruzzi 2014 {published data only}
    1. Petruzzi M, Lucchese A, Nardi GM, Lauritano D, Favia G, Serpico R, et al. Evaluation of autofluorescence and toluidine blue in the differentiation of oral dysplastic and neoplastic lesions from non-dysplastic and neoplastic lesions: a cross-sectional study. Journal of Biomedical Optics 2014;19(7):76003. - PubMed
Rahman 2012 {published data only}
    1. Rahman F, Tippu SR, Khandelwal S, Girish KL, Manjunath BC, Bhargava A. A study to evaluate the efficacy of toluidine blue and cytology in detecting oral cancer and dysplastic lesions. Quintessence International 2012;43:51-9. - PubMed
Scheer 2011 {published data only}
    1. Scheer M, Neugebauer J, Derman A, Fuss J, Drebber U, Zoeller JE. Autofluorescence imaging of potentially malignant mucosa lesions. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 2011;111(5):568-77. - PubMed
Scheifele 2004 {published data only}
    1. Scheifele C, Schmidt-Westhausen AM, Dietrich T, Reichart PA. The sensitivity and specificity of the OralCDx technique: evaluation of 103 cases. Oral Oncology 2004;40(8):824-8. - PubMed
Sciubba 1999 {published data only}
    1. Sciubba JJ. Computer-assisted analysis of the oral brush biopsy. Journal of the American Dental Association 1999;130:1445-57. - PubMed
Seijas‐Naya 2012 {published data only}
    1. Seijas-Naya F, García-Carnicero T, Gandara-Vila P, Couso-Folgueiras E, Perez-Sayans M, Gandara-Vila R, et al. Applications of OralCDx methodology in the diagnosis of oral leukoplakia. Medicina Oral, Patologia Oral y Cirugia Bucal 2012;1(17):5-9. - PMC - PubMed
Sharwani 2006a {published data only}
    1. Sharwani A, Jerjes W, Salih V, MacRobert AJ, El-Maaytah M, Khalil HSM, et al. Fluorescence spectroscopy combined with 5-aminolevulinicacid-induced protoporphyrin IX fluorescence in detecting oral premalignancy. Journal of Photochemistry and Photobiology 2006;83:27-33. - PubMed
Sharwani 2006b {published data only}
    1. Sharwani A, Jerjes W, Salih V, Swinson B, Bigio IJ, El-Maaytah M, et al. Assessment of oral premalignancy using elastic scattering spectroscopy. Oral Oncology 2006;42:343-9. - PubMed
Shi 2019 {published data only}
    1. Shi L, Li C, Shen X, Zhou Z, Liu W, Tang G. Potential role of autofluorescence imaging in determining biopsy of oral potentially malignant disorders: a large prospective diagnostic study. Oral Oncology 2019;98:176-9. - PubMed
Shukla 2018 {published data only}
    1. Shukla A, Singh NN, Adsul S, Kumar S, Shukla D, Sood A. Comparative efficacy of chemiluminescence and toluidine blue in the detection of potentially malignant and malignant disorders of the oral cavity. Journal of Oral and Maxillofacial Pathology 2018;22(3):442. - PMC - PubMed
Silverman 1984 {published data only}
    1. Silverman S, Migliorati C, Barbosa J. Toluidine blue staining in the detection of oral precancerous and malignant lesions. Oral Surgery, Oral Medicine, and Oral Pathology 1984;57(4):379-82. - PubMed
Singh 2015 {published data only}
    1. Singh D, Shukla RK. Utility of toluidine blue test in accessing and detecting intraoral malignancies. Indian Journal of Otolaryngology and Head & Neck Surgery 2015;67 (Suppl 1):S47–S50. - PMC - PubMed
Skandarajah 2017 {published data only}
    1. Skandarajah A, Sunny SP, Gurpur P, Reber CD, Ambrosio MVD, Raghavan N, et al. Mobile microscopy as a screening tool for oral cancer in India: a pilot study. PLOS One 2017;12(11):e0188440. - PMC - PubMed
Svirsky 2002 {published data only}
    1. Svirsky JA, Burns JC, Carpenter WM, Cohen DM, Bhattacharyya I, Fantasia JE, et al. Comparison of computer-assisted brush biopsy results with follow-up scalpel biopsy and histology. General Dentistry 2002;50(6):500-3. - PubMed
Trakroo 2015 {published data only}
    1. Trakroo A, Sunil MK, Trivedi A, Garg R, Kulkarni A, Arora S. Efficacy of oral brush biopsy without computer-assisted analysis in oral premalignant and malignant lesions: a study. Journal of International Oral Health 2015;7(3):33-8. - PMC - PubMed
Ujaoney 2012 {published data only}
    1. Ujaoney S, Motwani MB, Degwekar S, Wadhwan V, Zade P, Chaudhary M, et al. Evaluation of chemiluminescence, toluidine blue and histopathology for detection of high risk oral precancerous lesions: a cross-sectional study. BMC Clinical Pathology 2012;12(6):1-7. - PMC - PubMed
Upadhyay 2011 {published data only}
    1. Upadhyay J, Rao NN, Upadhyay RB, Agarwal P. Reliability of toluidine blue vital staining in detection of potentially malignant oral lesions - time to reconsider. Asian Pacific Journal of Cancer Prevention 2011;12:1757-60. - PubMed
Warnakulasuriya 1996 {published data only}
    1. Warnakulasuriya KAAS, Johnson NW. Sensitivity and specificity of OraScan toluidine blue mouthrinse in the detection of oral cancer and precancer. Journal of Oral Pathology and Medicine 1996;25:97-103. - PubMed
Yamamoto 2017 {published data only}
    1. Yamamoto N, Kawaguchi K, Fujihara H, Hasebe M, Kishi Y, Yasukawa M, et al. Detection accuracy for epithelial dysplasia using an objective autofluorescence visualization method based on the luminance ratio. International Journal of Oral Science 2017;9(11):e2. - PMC - PubMed

References to studies excluded from this review

Abram 2019 {published data only}
    1. Abram TJ, Floriano PN, James R, Kerr AR, Thornhill MH, Redding SW, et al. Development of a cytology-based multivariate analytical risk index for oral cancer. Oral Oncology 2019;92:6-11. - PMC - PubMed
Betz 2002 {published data only}
    1. Betz CS, Stepp H, Janda P, Arbogast S, Grevers G, Baumgartner R, et al. A comparative study of normal inspection, autofluorescence and 5-ALA-induced PPIX fluorescence for oral cancer diagnosis. International Journal of Cancer 2002;97(2):245-52. - PubMed
Bhoopathi 2009 {published data only}
    1. Bhoopathi V, Kabani S, Mascarenhas AK. Low positive predictive value of the oral brush biopsy in detecting dysplastic oral lesions. Cancer 2009;115(5):1036-40. - PubMed
Burkhardt 2010 {published data only}
    1. Burkhardt A. A response to “sensitivity and specificity of oral brush biopsy” by Hohlweg-Majert et al. Cancer Investigation 2010;28(5):560-1. - PubMed
CTRI/2020/01/022999 {published data only}
    1. CTRI/2020/01/022999. Usefulness of newly developed light emitting device for screening of precancer and cancer [Validation of novel light emitting device for screening of potential malignant oral disorders and oral cancer]. www.ctri.nic.in/Clinicaltrials/showallp.php?mid1=37933&EncHid=&u... (first received 27 January 2020).
Deuerling 2019 {published data only}
    1. Deuerling L, Gaida K, Neumann H, Remmerbach TW. Evaluation of the accuracy of liquid-based oral brush cytology in screening for oral squamous cell carcinoma. Cancers 2019;11(11):1813. - PMC - PubMed
Driemel 2007 {published data only}
    1. Driemel O, Dahse R, Hakim SG, Tsioutsias T, Pistner H, Reichert TE, et al. Laminin-5 immunocytochemistry: a new tool for identifying dysplastic cells in oral brush biopsies. Cytopathology 2007;18(6):348-55. - PubMed
Driemel 2007b {published data only}
    1. Driemel O, Dahse R, Berndt A, Pistner H, Hakim SG, Zardi L, et al. High-molecular tenascin-C as an indicator of atypical cells in oral brush biopsies. Clinical Oral Investigations 2007;11:93-9. - PubMed
Driemel 2008 {published data only}
    1. Driemel O, Kunkel M, Hullmann M, Kleinsasser N, Staudenmaier R, Muller-Richter U, et al. Performance of conventional oral brush biopsies [Wertigkeit der konventionellen oralen Bürstenbiopsie]. HNO 2008;56:205-10. - PubMed
Ebenezar 2012 {published data only}
    1. Ebenezar J, Ganesan S, Aruna P, Muralinaidu R, Renganathan K, Saraswathy TR. Non-invasive fluorescence excitation spectroscopy for the diagnosis of oral neoplasia in vivo. Journal of Biomedical Optics 2012;17(9):97007. - PubMed
Epstein 1995 {published data only}
    1. Epstein JB, Fatahzadeh M, Matisic J, Anderson G. Exfoliative cytology and electron microscopy in the diagnosis of hairy leukoplakia. Oral Surgery, Oral Medicine, Oral Pathology 1995;79(5):565-9. - PubMed
Gomez Serrano 1989 {published data only}
    1. Gomez Serrano MT, Fernandez JMT, Bravo JM. Toluidine blue solution as diagnostic aid in oropharyngeal cancer [Azul de toludina en enjuagues, como auxiliar diagnóstico de cancer orofaríngeo]. Revista ADM 1989;46(1):29-35. - PubMed
Hedge 2006 {published data only}
    1. Hegde MC, Kamath PM, Shreedharan S, Dannana NK, Raju RM. Supravital staining: its role in detecting early malignancies. Indian Journal of Otolaryngology and Head & Neck Surgery 2006;58(1):31-4. - PMC - PubMed
Hohlwleg‐Majert 2009 {published data only}
    1. Hohlweg-Majert B, Deppe H, Metzger MC, Schumm S, Hoefler H, Kesting MR, et al. Sensitivity and specificity of oral brush biopsy. Cancer Investigation 2009;27:293-7. - PubMed
Jayaprakash 2009 {published data only}
    1. Jayaprakash V, Sullivan M, Merzianu M, Rigual NR, Loree TR, Popat SR, et al. Autofluorescence-guided surveillance for oral cancer. Cancer Prevention Research 2009;11(2):966-74. - PMC - PubMed
Kulapaditharon 1998 {published data only}
    1. Kulapaditharom B, Boonkitticharroen V. Laser-induced fluorescence imaging in localization of head and neck cancers. Annals of Otology, Rhinology & Laryngology 1998;107(3):241-6. - PubMed
Lane 2012 {published data only}
    1. Lane P, Lam S, Follen M, MacAulay C. Oral fluorescence imaging using 405-nm excitation, aiding the discrimination of cancers and precancers by identifying changes in collagen and elastic breakdown and neovascularization in the underlying stroma. Gender Medicine 2012;9(1):S78-82.e8. - PubMed
Levine 1998 {published data only}
    1. Levine TS, Njemenze V, Cowpe JG, Coleman FV. The use of PAPNET automated cytological screening system for the diagnosis of oral squamous carcinoma. Cytopathology 1998;9(6):398-405. - PubMed
Li 2004 {published data only}
    1. Li Y, St John MA, Zhou X, Kim Y, Sinha U, Jordan RC, et al. Salivary transcriptome diagnostics for oral cancer detection. Clinical Cancer Research 2004;10(24):8442-50. - PubMed
Majumder 2006 {published data only}
    1. Majumder SK, Gupta A, Gupta S, Ghosh N, Gupta PK. Multi-class classification algorithm for optical diagnosis of oral cancer. Journal of Photochemistry and Photobiology 2006;85(2):109-17. - PubMed
Mallia 2010b {published data only}
    1. Mallia RJ, Narayanan S, Madhavan J, Sebastian P, Kumar R, Mathews A, et al. Diffuse reflection spectroscopy: an alternative to autofluorescence spectroscopy in tongue cancer detection. Applied Spectroscopy 2010;64(4):409-13. - PubMed
Maraki 2004 {published data only}
    1. Maraki D, Becker J, Boecking A. Cytologic and DNA-cytometric very early diagnosis of oral cancer. Journal of Oral Pathology and Medicine 2004;33:398-404. - PubMed
Maraki 2006 {published data only}
    1. Maraki D, Yalcinkaya S, Pomjanski N, Megahed M, Boecking A, Becker J. Cytologic and DNA-cytometric examination of oral lesions in lichen planus. Journal of Oral Pathology and Medicine 2006;35(4):227-32. - PubMed
Navone 2007 {published data only}
    1. Navone R, Burlo P, Pich A, Pentenero M, Broccoletti R, Marsico A, et al. The impact of liquid-based oral cytology on the diagnosis of oral squamous dysplasia and carcinoma. Cytopathology 2007;18(6):356-60. - PubMed
Navone 2009 {published data only}
    1. Navone R. Cytology of the oral cavity: a re-evaluation. Pathologica 2009;101:6-B. - PubMed
Nieman 2008 {published data only}
    1. Nieman LT, Kan CW, Gillenwater A, Markey MK, Sokolov K. Probing local tissue changes in the oral cavity for early detection of cancer using oblique polarized reflectance spectroscopy: a pilot clinical trial. Journal of Biomedical Optics 2008;13(2):24011-1. - PubMed
Poate 2004 {published data only}
    1. Poate TWJ, Buchanan JAG, Hodgson TA, Speight PM, Barrett AW, Moles DR, et al. An audit of the efficacy of the oral brush biopsy technique in a specialist oral medicine unit. Oral Oncology 2004;40:829-34. - PubMed
Rana 2012 {published data only}
    1. Ranaa M, Zapfb A, Kuehlea M, Gellrichaand NC, Eckardta AM. Clinical evaluation of an autofluorescence diagnostic device for oral cancer detection: a prospective randomized diagnostic study. European Journal of Cancer Prevention 2012;21(5):460-6. - PubMed
Reboires‐Lopez 2012 {published data only}
    1. Reboiras-López MD, Pérez-Sayáns M, Somoza-Martín JM, Gayoso-Diz P, Barros-Angueira F, Gándara-Rey JM, et al. Comparison of the Cytobrush, dermatological curette and oral CDx brush test as methods for obtaining samples of RNA for molecular analysis of oral cytology. Cytopathology 2011;23(3):192-7. - PubMed
Remmerbach 2001 {published data only}
    1. Remmerbach TW, Weidenbach H, Pomjanski N, Knops K, Mathes S, Hemprich A, et al. Cytologic and DNA-cytometric early diagnosis of oral cancer. Analytical Cellular Pathology 2001;22(4):211-21. - PMC - PubMed
Remmerbach 2003 {published data only}
    1. Remmerbach TW, Weidenbach H, Müller C, Hemprich A, Pomjanski N, Buckstegge B, et al. Diagnostic value of nucleolar organizer regions (AgNORs) in brush biopsies of suspicious lesions of the oral cavity. Analytical Cellular Pathology 2003;25(3):139-46. - PMC - PubMed
Remmerbach 2004 {published data only}
    1. Remmerbach TW, Mathes SN, Weidenbach H, Hemprich A, Bocking A. Non-invasive brush biopsy as an innovative tool for early detection of oral carcinomas [Nichtinvasive Bürstenbiopsie als innovative Methodein der Früherkennung des Mundhöhlenkarzinoms]. Mund Kiefer und GesichtsChirurgie 2004;8:229-36. - PubMed
Remmerbach 2007 {published data only}
    1. Remmerbach TW, Hemprich A, Bocking A. [Minimalinvasive Bürstenbiopsie]. Praxis Fortbildung 2007;117:926-40. - PubMed
Remmerbach 2009 {published data only}
    1. Remmerbach TW, Meyer-Ebrecht D, Aach T, Wurflinger T, Bell AA, Schneider TE, et al. Toward a multimodal cell analysis of brush biopsies for the early detection of oral cancer. Cancer Cytopathology 2009;117(3):228-35. - PubMed
Sahu 2017 {published data only}
    1. Sahu A, Gera P, Pai V, Dubey A, Tyagi G, Waghmare M, et al. Raman exfoliative cytology for oral precancer diagnosis. Journal of Biomedical Optics 2017;22(11):1-12. - PubMed
Sandler 1964 {published data only}
    1. Sandler HC. Reliability of oral exfoliative cytology for detection of oral cancer. Journal of the American Dental Association 1964;68:489-99. - PubMed
Schwarz 2009 {published data only}
    1. Schwarz RA, Gao W, Redden Weber C, Kurachi C, Lee JJ, El-Naggar AK, et al. Non-invasive evaluation of oral lesions using depth-sensitive optical spectroscopy. Cancer 2009;115(8):1669-79. - PMC - PubMed
Sekine 2017 {published data only}
    1. Sekine J, Nakatani E, Hideshima K, Iwahashi T, Sasaki H. Diagnostic accuracy of oral cancer cytology in a pilot study. Diagnostic Pathology 2017;12(1):27. - PMC - PubMed
Shklar 1970 {published data only}
    1. Shklar G, Cataldo E, Meyer I. Reliability of cytologic smear in diagnosis of oral cancer. A controlled study. Archives of Otolaryngology 1970;91(2):158-60. - PubMed
Silverman 1992 {published data only}
    1. Silverman S, Migliorati C. Toluidine blue staining and early detection of oral precancerous and malignant lesions. Iowa Dental Journal 1992;78(2):15-6. - PubMed
Simonato 2017 {published data only}
    1. Simonato LE, Tomo S, Miyahara GI, Navarro RS, Villaverde AGJB. Fluorescence visualization efficacy for detecting oral lesions more prone to be dysplastic and potentially malignant disorders: a pilot study. Photodiagnosis and Photodynamic Therapy 2017;17:1-4. - PubMed
Sun 2019 {published data only}
    1. Sun Z, Liu L, Wang C, Qian L, Yang J, Zhao Z, et al. Assessment of the cancerization risk for oral potentially malignant disorders by clinical risk model combined with autofluorescence and brush biopsy with DNA-image cytometry. European Archives of Oto-rhino-laryngology 2019;276(9):2549-57. - PubMed
Swider 1984 {published data only}
    1. Swider M, Nakwer K, Wierzbicki J, Grudzinska J. Toluidine test in the diagnosis of oral cancer. Czasopismo Stomatologiczne 1984;37(9):669-703. - PubMed
Torres‐Rendon 2009 {published data only}
    1. Torres-Rendon A, Stewart R, Craig GT, Wells M, Speight PM. DNA ploidy analysis by image cytometry helps to identify oral epithelial dysplasias with a high risk of malignant progression. Oral Oncology 2009;45:468-73. - PubMed
Uthoff 2018 {published data only}
    1. Uthoff RD, Song B, Sunny S, Patrick S, Suresh A, Kolur T, et al. Point-of-care, smartphone-based, dual-modality, dual-view, oral cancer screening device with neural network classification for low-resource communities. PLOS One 2018;13(12):e0207493. - PMC - PubMed
Wang 2009 {published data only}
    1. Wang CY, Tsai T, Chiang CP, Chen HM, Chen CT. Improved diagnosis of oral premalignant lesions in submucous fibrosis patients with 5-aminolevulinic acid induced PpIX fluorescence. Journal of Biomedical Optics 2009;14(4):044026. - PubMed
Yang 2017 {published data only}
    1. Yang X, Xiao X, Wu W, Shen X, Zhou Z, Liu W, et al. Cytological study of DNA content and nuclear morphometric analysis for aid in the diagnosis of high-grade dysplasia within oral leukoplakia. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 2017;124(3):280-5. - PubMed

References to ongoing studies

CTRI/2018/02/012257 {unpublished data only}
    1. CTRI/2018/02/012257. Oral cancer early detection project, a population based study [Early identification of potentially malignant and malignant lesions using clinical oral examination and VELscope on large population]. www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=22747&EncHid=&a... (first received 28 February 2018).
CTRI/2019/02/017623 {unpublished data only}
    1. CTRI/2019/02/017623. Developing an efficient and cost effective method for screening of oral cancer in India [A pilot study to develop an efficacious oral cancer screening strategy for India]. www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=29546&EncHid=&a... (first received 12 February 2019).
CTRI/2019/11/022167 {published data only}
    1. CTRI/2019/11/022167. Mobile oral cancer screening in limited resource setting [Low-cost mobile oral cancer screening for low resource setting]. www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=37024&EncHid=&a... (first received 27 November 2019).

Additional references

Abram 2016
    1. Abram TJ, Floriano PN, Christodoulides N, James R, Kerr AR, Thornhill MH, et al. 'Cytology-on-a-chip' based sensors for monitoring of potentially malignant oral lesions. Oral Oncology 2016;60:103-11. - PMC - PubMed
AlAli 2020
    1. AlAli AM, Walsh T, Maranzano M. CYFRA 21-1 and MMP-9 as salivary biomarkers for the detection of oral squamous cell carcinoma: a systematic review of diagnostic test accuracy. International Journal of Oral and Maxillofacial Surgery 2020;49(8):973-83. - PubMed
Arduino 2013
    1. Arduino PG, Bagan J, El-Naggar AK, Carrozzo M. Urban legends series: oral leukoplakia. Oral Diseases 2013;19(7):642-59. - PubMed
Bagan 2020
    1. Bagan JV, Bagan-Debon L. Clinical presentation and differential diagnosis of oral cancer. In: Warnakulasuriya S, Greenspan JS, editors(s). Textbook of Oral Cancer. Switzerland: Springer Nature, 2020:47-54.
Bossuyt 2003
    1. Bossuyt, PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM, et al. The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Annals of Internal Medicine 2003;138(1):W1-12. - PubMed
Bravi 2021
    1. Bravi F, Lee YA, Hashibe M, Boffetta P, Conway DI, Ferraroni M, et al. Lessons learned from the INHANCE consortium: an overview of recent results on head and neck cancer. Oral Diseases 2021;27(1):73-93. - PMC - PubMed
Bray 2018
    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians 2018;68(6):394–424. - PubMed
Brinkmann 2011
    1. Brinkmann O, Kastratovic DA, Dimitrijevic MV, Konstantinovic VS, Jelovac DB, Antic J, et al. Oral squamous cell carcinoma detection by salivary biomarkers in a Serbian population. Oral Oncology 2011;47(1):51-5. - PMC - PubMed
Brocklehurst 2013
    1. Brocklehurst P, Kujan O, O’Malley LA, Ogden G, Shepherd S, Glenny AM. Screening programmes for the early detection and prevention of oral cancer. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No: CD004150. [DOI: 10.1002/14651858.CD004150.pub3] - DOI - PMC - PubMed
Buchen 2011
    1. Buchen L. Cancer: missing the mark. Nature 2011;471(7339):428-32. - PubMed
Bulsara 2018
    1. Bulsara VM, Worthington HV, Glenny AM, Clarkson JE, Conway DI, Macluskey M. Interventions for the treatment of oral and oropharyngeal cancers: surgical treatment. Cochrane Database of Systematic Reviews 2018, Issue 12. Art. No: CD006205. [DOI: 10.1002/14651858.CD006205.pub4] - DOI - PMC - PubMed
Cancer Research UK
    1. Cancer Research UK. Oral cancer statistics. www.cancerresearchuk.org/cancer-info/cancerstats/types/oral (accessed 8 April 2011).
Chaturvedi 2019
    1. Chaturvedi AK, Udaltsova N, Engels EA, Katzel JA, Yanik EL, Katki HA, et al. Oral leukoplakia and risk of progression to oral cancer: a population-based cohort study. Journal of the National Cancer Institute 2020;112(10):1047-54. - PMC - PubMed
Chi 2015
    1. Chi AC, Day TA, Neville BW. Oral cavity and oropharyngeal squamous cell carcinoma - an update. CA: a Cancer Journal for Clinicians 2015;65(5):401-21. - PubMed
Chu 2006
    1. Chu H, Cole SR. Bivariate meta-analysis for sensitivity and specificity with sparse data: a generalized linear mixed model approach (letter to the Editor). Journal of Clinical Epidemiology 2006;59(12):1331-2. - PubMed
de Pauli Paglioni 2020
    1. Pauli Paglioni M, Migliorati CA, Schausltz Pereira Faustino I, Linhares Almeida Mariz BA, Oliveira Corrêa Roza AL, Agustin Vargas P, et al. Laser excision of oral leukoplakia: does it affect recurrence and malignant transformation? A systematic review and meta-analysis. Oral Oncology 2020;109:104850. [DOI: ] - PubMed
Dinnes 2016
    1. Dinnes J, Mallett S, Hopewell S, Roderick PJ, Deeks JJ. The Moses–Littenberg meta-analytical method generates systematic differences in test accuracy compared to hierarchical meta-analytical models. Journal of Clinical Epidemiology 2016;80:77-87. - PMC - PubMed
Divani 2009
    1. Divani S, Exarhou M, Theodorou LN, Georgantzis D, Skoulakis H. Advantages and difficulties of brush cytology in the identification of early oral cancer. Archive of Oncology 2009;17(1-2):11-2.
Dost 2014
    1. Dost F, Lê Cao K, Ford PJ, Ades C, Farah CS. Malignant transformation of oral epithelial dysplasia: a real-world evaluation of histopathologic grading. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 2014;117(3):343-52. - PubMed
ERO‐FDI 2019
    1. Perks A, Forna DA, Barreira E, Fricain JC, Monteiro L, Diniz Freitas M, et al. Oral Cancer Prevention. European Regional Organization of the Federation Dentaire Internationale (FDI), 2019.
Farah 2019
    1. Farah CS, Shearston K, Nguyen AP, Kujan O. Oral carcinogenesis and malignant transformation. In: Brennan PA, Aldridge T, Dwivedi RC, editors(s). Premalignant Conditions of the Oral Cavity. Singapore: Springer Singapore, 2019:27-66.
Fedele 2009
    1. Fedele S. Diagnostic aids in the screening of oral cancer. Head and Neck Oncology 2009;1:5. - PMC - PubMed
Ferlay 2010
    1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. International Journal of Cancer 2010;127(12):2893-917. - PubMed
Fitzpatrick 2014
    1. Fitzpatrick SG, Hirsch SA, Gordon SC. The malignant transformation of oral lichen planus and oral lichenoid lesions: a systematic review. Journal of the American Dental Association 2014;145(1):45-56. - PubMed
Furness 2011
    1. Furness S, Glenny AM, Worthington HV, Pavitt S, Oliver R, Clarkson JE, et al. Interventions for the treatment of oral cavity and oropharyngeal cancer: chemotherapy. Cochrane Database of Systematic Reviews 2011, Issue 4. Art. No: CD006386. [DOI: 10.1002/14651858.CD006386.pub3] - DOI - PubMed
Ganly 2012
    1. Ganly I, Patel S, Shah J. Early stage squamous cell cancer of the oral tongue - clinicopathologic features affecting outcome. Cancer 2012;118(1):101-11. - PubMed
Garg 2005
    1. Garg AX, Adhikari NK, McDonald H, Rosas-Arellano MP, Devereaux PJ, Beyene J, et al. Effects of computerized clinical decision support systems on practitioner performance and patient outcomes: a systematic review. JAMA 2005;293(10):1223-38. - PubMed
Giuliani 2019
    1. Giuliani M, Troiano G, Cordaro M, Corsalini M, Gioco G, Lo Muzio L, et al. Rate of malignant transformation of oral lichen planus: a systematic review. Oral Diseases 2019;25(3):693-709. - PubMed
Glenny 2010
    1. Glenny AM, Furness S, Worthington HV, Conway DI, Oliver R, Clarkson JE, et al. Interventions for the treatment of oral cavity and oropharyngeal cancer: radiotherapy. Cochrane Database of Systematic Reviews 2010, Issue 12. Art. No: CD006387. [DOI: 10.1002/14651858.CD006387.pub2] - DOI - PMC - PubMed
González‐Moles 2019
    1. González-Moles MÁ, Ruiz-Ávila I, González-Ruiz L, Ayén Á, Gil-Montoya JA, Ramos-García P. Malignant transformation risk of oral lichen planus: a systematic review and comprehensive meta-analysis. Oral Oncology 2019;86:121-30. - PubMed
Harbord 2009
    1. Harbord RM, Whiting P. Metandi: meta-analysis of diagnostic accuracy using hierarchical logistic regression. Stata Journal 2009;9(2):211-29.
Holmstrup 2006
    1. Holmstrup P, Vedtofte P, Reibel J, Stoltze K. Long-term treatment outcome of oral premalignant lesions. Oral Oncology 2006;42(5):461-74. - PubMed
IARC 2012
    1. World Health Organization, International Agency for Research on Cancer (IARC). Personal habits and indoor combustions. Lyon (France): IARC Monographs on the Evaluation of Carcinogenic Risks to Humans; 2012. Volume 100E; I2012. - PMC - PubMed
Idrees 2021
    1. Idrees M, Kujan O, Shearston K, Farah CS. Oral lichen planus has a very low malignant transformation rate: a systematic review and meta-analysis using strict diagnostic and inclusion criteria. Journal of Oral Pathology & Medicine 2021;50(3):287-98. - PubMed
Jin 2016
    1. Jin LJ, Lamster IB, Greenspan JS, Pitts NB, Scully C, Warnakulasuriya S. Global burden of oral diseases: emerging concepts, management and interplay with systemic health. Oral Diseases 2016;22(7):609-19. - PubMed
Kerr 2020
    1. Kerr AR. Diagnostic adjuncts for oral cavity squamous cell carcinoma and oral potentially malignant disorders. In: Warnakulasuriya S, Greenspan JS, editors(s). Textbook of Oral Cancer. Switzerland: Springer Nature, 2020:99-118.
Kreimer 2020
    1. Kreimer AR, Chaturvedi AK, Alemany L, Anantharaman D, Bray F, Carrington M, et al. Summary from an international cancer seminar focused on human papillomavirus (HPV)-positive oropharynx cancer, convened by scientists at IARC and NCI. Oral Oncology 2020;108:104736. - PMC - PubMed
Landis 1977
    1. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977;33(1):159-74. - PubMed
Lee 2009
    1. Lee JM, Garon E, Wong DT. Salivary diagnostics. Orthodontics and Craniofacial Research 2009;12(3):206-11. - PMC - PubMed
Leeflang 2008
    1. Leeflang MM, Deeks JJ, Gatsonis C, Bossuyt PM, Cochrane Diagnostic Test Accuracy Working Group. Systematic reviews of diagnostic test accuracy. Annals of Internal Medicine 2008;149(12):889-97. - PMC - PubMed
Leston 2010
    1. Seoane Lestón J, Diz Dios P. Diagnostic clinical aids in oral cancer. Oral Oncology 2010;46(6):418-22. - PubMed
Li 2006
    1. Li Y, Elashoff D, Oh M, Sinha U, St John MA, Zhou X, et al. Serum circulating human mRNA profiling and its utility for oral cancer detection. Journal of Clinical Oncology 2006;24(11):1754-60. - PubMed
Lim 2003
    1. Lim K, Moles DR, Speight PM. Opportunistic screening for oral cancer and precancer in general dental practice: results of a demonstration study. British Dental Journal 2003;194:497–502. - PubMed
Lingen 2008
    1. Lingen MW, Kalmar JR, Karrison T, Speight PM. Critical evaluation of diagnostic aids for the detection of oral cancer. Oral Oncology 2008;44(1):10-22. - PMC - PubMed
Lingen 2017
    1. Lingen MW, Tampi MP, Urquhart O, Abt E, Agrawal N, Chaturvedi AK, et al. Adjuncts for the evaluation of potentially malignant disorders in the oral cavity: diagnostic test accuracy systematic review and meta-analysis - a report of the American Dental Association. Journal of the American Dental Association 2017;148(11):797-813. - PMC - PubMed
Liu 2006
    1. Liu JL, Wyatt JC, Deeks JJ, Clamp S, Keen J, Verde P, et al. Systematic reviews of clinical decision tools for acute abdominal pain. Health Technology Assessment 2006;10(47):1-167. - PubMed
Liu 2016
    1. Liu D, Zhao X, Zeng X, Dan H, Chen Q. Non-invasive techniques for detection and diagnosis of oral potentially malignant disorders. Tohoku Journal of Experimental Medicine 2016;238(2):165-77. - PubMed
Locca 2020
    1. Locca O, Sollecito TP, Alawi F, Weinstein GS, Newman JG, De Virgilio A, et al. Potentially malignant disorders of the oral cavity and oral dysplasia: a systematic review and meta-analysis of malignant transformation rate by subtype. Head & Neck 2020;42(3):539-55. - PubMed
Lodi 2006
    1. Lodi G, Sardella A, Bez C, Demarosi F, Carrassi A. Interventions for treating oral leukoplakia. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No: CD001829. [DOI: 10.1002/14651858.CD001829.pub3] - DOI - PubMed
Lodi 2016
    1. Lodi G, Franchini R, Warnakulasuriya S, Varoni EM, Sardella A, Kerr AR, et al. Interventions for treating oral leukoplakia to prevent oral cancer. Cochrane Database of Systematic Reviews 2016, Issue 7. Art. No: CD001829. [DOI: 10.1002/14651858.CD001829.pub4] - DOI - PMC - PubMed
Macaskill 2011
    1. Macaskill P, Gatsonis C, Deeks JJ, Harbord RM, Takwoingi Y. Chapter 10: Analysing and presenting results. In: Deeks JJ, Bossuyt PM, Gatsonis C, editor(s). Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy Version 1.0. The Cochrane Collaboration, 2011. Available from methods.cochrane.org/sdt/handbook-dta-reviews.
Madhura 2020
    1. Madhura MG, Rao RS, Patil S, Fageeh HN, Alhazmi A, Awan KH. Advanced diagnostic aids for oral cancer. Disease-a-month 2020;66(12):101034. [DOI: 10.1016/j.disamonth.2020.101034] - DOI - PubMed
McRae 2020
    1. McRae MP, Modak SS, Simmons GW, Trochesset DA, Kerr AR, Thornhill MH, et al. Point-of-care oral cytology tool for the screening and assessment of potentially malignant oral lesions. Cancer Cytopathology 2020;128(3):207-20. - PMC - PubMed
Mehanna 2009
    1. 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):1600-9. - PubMed
Miranda‐Filho 2020
    1. Miranda-Filho A, Bray F. Global patterns and trends in cancers of the lip, tongue and mouth. Oral Oncology 2020;102:104551. [DOI: 10.1016/j.oraloncology.2019.104551] - DOI - PubMed
NICE 2016
    1. National Institute for Health and Care Excellence (NICE). Head and neck cancers - recognition and referral. cks.nice.org.uk/topics/head-neck-cancers-recognition-referral/ 2016.
Nikitakis 2018
    1. Nikitakis NG, Pentenero M, Georgaki M, Poh CF, Peterson DE, Edwards P, et al. Molecular markers associated with development and progression of potentially premalignant oral epithelial lesions: current knowledge and future implications. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 2018;125(6):650-69. - PubMed
Ogden 1994
    1. Ogden GR, Cowpe JG, Chisholm DM, Lane EB. DNA and keratin analysis of oral exfoliative cytology in the detection of oral cancer. Oral Oncology, European Journal of Cancer 1994;30B:405-8. - PubMed
Ogden 2015
    1. Ogden GR, Scully C, Warnakulasuriya S, Speight P. Oral cancer: two cancer cases in a career? British Dental Journal 2015;218:439. - PubMed
Ogden 2020
    1. Ogden GR. Factors affecting survival for oral cancer. In: Warnakulasuriya S, Greenspan JS, editors(s). Textbook of Oral Cancer. Switzerland: Springer Nature, 2020:327-42.
Omar 2015
    1. Omar E. Current concepts and future of non-invasive procedures for diagnosing oral squamous cell carcinoma - a systematic review. Head & Face Medicine 2015;11:6. - PMC - PubMed
Park 2009
    1. Park NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E, et al. Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clinical Cancer Research 2009;15(17):5473-7. - PMC - PubMed
Parkin 2001
    1. Parkin DM. Global cancer statistics in the year 2000. Lancet Oncology 2001;2(9):533-43. - PubMed
Patton 2008
    1. Patton LL, Epstein JB, Kerr AR. Adjunctive techniques for oral cancer examination and lesion diagnosis: a systematic review of the literature. Journal of the American Dental Association 2008;139(7):896-905. - PubMed
Petti 2003
    1. Petti S. Pooled estimate of world leukoplakia prevalence: a systematic review. Oral Oncology 2003;39(8):770-80. - PubMed
Purkayastha 2018
    1. Purkayastha M, McMahon A, Gibson J, Conway DI. Is detecting oral cancer in general dental practices a realistic expectation? A population-based study using population linked data in Scotland. British Dental Journal 2018;225:241-6. - PubMed
Reitsma 2005
    1. Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. Journal of Clinical Epidemiology 2005;58(10):982-90. - PubMed
Rethman 2010
    1. Rethman MP, Carpenter W, Cohen EE, Epstein J, Evans CA, Flaitz CM, et al. Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas. Journal of the American Dental Association 2010;141(5):509-20. - PubMed
Review Manager 2020 [Computer program]
    1. Review Manager 5 (RevMan 5). Version 5.4. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2020.
Rusthoven 2010
    1. Rusthoven KE, Raben D, Song JI, Kane M, Altoos TA, Chen C. Survival and patterns of relapse in patients with oral tongue cancer. Journal of Oral and Maxillofacial Surgery 2010;68(3):584-9. - PubMed
Schünemann 2020
    1. Schünemann HJ, Mustafa RA, Brozek J, Steingart KR, Leeflang M, Murad MH, et al. Study design, risk of bias, and indirectness in rating the certainty across a body of evidence for test accuracy. Journal of Clinical Epidemiology 2020;122:129-41. - PubMed
Schünemann 2020a
    1. Schünemann HJ, Mustafa RA, Brozek J, Steingart KR, Leeflang M, Murad MH, et al. GRADE guidelines: 21 part 2. Test accuracy: inconsistency, imprecision, publication bias, and other domains for rating the certainty of evidence and presenting it in evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 2020;122:142-52. - PubMed
Seoane 2016
    1. Seoane J, Alvarez-Novoa P, Gomez I, Takkouche B, Diz P, Warnakulasiruya S, et al. Early oral cancer diagnosis: the Aarhus statement perspective. A systematic review and meta-analysis. Head & Neck 2016;38 Suppl 1:E2182-9. - PubMed
Shaw 2020
    1. Shaw RJ, O’Connell JE, Bajwa M. Basic surgical principles and techniques. In: Warnakulasuriya S, Greenspan JS, editors(s). Textbook of Oral Cancer. Switzerland: Springer Nature, 2020:253-82.
Shi 2019
    1. Shi L, Li C, Shen X, Zhou Z, Liu W, Tang G. Potential role of autofluorescence imaging in determining biopsy of oral potentially malignant disorders: a large prospective diagnostic study. Oral Oncology 2019;98:176-9. - PubMed
Shield 2017
    1. Shield KD, Ferlay J, Jemal A, Sankaranarayanan R, Chaturvedi AK, Bray F, et al. The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012. CA: a Cancer Journal for Clinicians 2017;67(1):51-6. - PubMed
Speight 2017
    1. Speight PM, Epstein J, Kujan O, Lingen MW, Nagao T, Ranganathan K, et al. Screening for oral cancer - a perspective from the Global Oral Cancer Forum. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 2017;123(6):680-7. - PubMed
Takwoingi 2016
    1. Takwoingi Y. Meta-analysis of test accuracy studies in Stata: a bivariate model approach. Version 1.1. methods.cochrane.org/sdt/ 2016.
Tang 2000
    1. Tang JL, Liu JL. Misleading funnel plot for detection of bias in meta-analysis. Journal of Clinical Epidemiology 2000;53(5):477-84. - PubMed
Thompson 2017
    1. Thomson PJ, Goodson ML, Smith DR. Profiling cancer risk in oral potentially malignant disorders - a patient cohort study. Journal of Oral Pathology & Medicine 2017;46(10):888-95. - PubMed
Tiwari 2019
    1. Tiwari L, Kujan O, Farah CS. Optical fluorescence imaging in oral cancer and potentially malignant disorders: a systematic review. Oral Diseases 2020;26(3):491-510. - PubMed
Walsh 2013
    1. Walsh T, Liu JLY, Brocklehurst P, Glenny AM, Lingen M, Kerr AR, et al. Clinical assessment to screen for the detection of oral cavity cancer and potentially malignant disorders in apparently healthy adults. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No: CD010173. [DOI: 10.1002/14651858.CD010173.pub2] - DOI - PMC - PubMed
Warnakulasuriya 2007
    1. Warnakulasuriya S, Johnson NW, Waal I. Nomenclature and classification of potentially malignant disorders of the oral mucosa. Journal of Oral Pathology and Medicine 2007;36(10):575-80. - PubMed
Warnakulasuriya 2009
    1. Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncology 2009;45(4-5):309-16. - PubMed
Warnakulasuriya 2011
    1. Warnakulasuriya S, Kovacevic T, Madden P, Coupland VH, Sperandio M, Odell E, et al. Factors predicting malignant transformation in oral potentially malignant disorders among patients accrued over a 10-year period in South East England. Journal of Oral Pathology and Medicine 2011;40(9):677-83. - PubMed
Warnakulasuriya 2016
    1. Warnakulasuriya S, Ariyawardana A. Malignant transformation of oral leukoplakia: a systematic review of observational studies. Journal of Oral Pathology and Medicine 2016;45(3):155-6. - PubMed
Warnakulasuriya 2020
    1. Warnakulasuriya S, Greenspan JS. Epidemiology of oral and oropharyngeal cancers. In: Warnakulasuriya S, Greenspan JS, editors(s). Textbook of Oral Cancer. Springer Nature: Switzerland, 2020:5-22.
Whiting 2011
    1. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Annals of Internal Medicine 2011;155(8):529-36. - PubMed
Wyatt 1995
    1. Wyatt JC, Altman DG. Commentary: prognostic models: clinically useful or quickly forgotten? BMJ 1995;311(7019):1539-41.

References to other published versions of this review

Liu 2012
    1. Liu JLY, Walsh T, Kerr AR, Lingen M, Brocklehurst P, Ogden G, et al. Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No: CD010276. [DOI: 10.1002/14651858.CD010276] - DOI - PMC - PubMed
Macey 2015
    1. Macey R, Walsh T, Brocklehurst P, Kerr AR, Liu JLY, Lingen MW, et al. Diagnostic tests for oral cancer and potentially malignant disorders in patients presenting with clinically evident lesions. Cochrane Database of Systematic Reviews 2015, Issue 5. Art. No: CD010276. [DOI: 10.1002/14651858.CD010276.pub2] - DOI - PMC - PubMed

Publication types