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Table 2 Analysis of studies addressing key questions 1, 2, 3 or 4 that met the inclusion criteria

From: Current concepts and future of noninvasive procedures for diagnosing oral squamous cell carcinoma - a systematic review

Study

Study or biopsy type(s)

Quality score

Type of study

Care setting

Country conducted in

Funded by

Number of patients enrolled

Epstein et al. 1997 [10]

Toluidine blue

7

Prospective

Department of Dentistry, British Columbia Cancer Agency

Canada

British Columbia Cancer Agency

-

Bouquot et al. 1986 [11]

Toluidine blue

6.5

Prospective

-

USA

-

23,616

Martin et al. 1998 [23]

Toluidine blue

6.3

-

Department of Oral and Facial Surgery, Sunderland Royal Hospital

UK

-

-

Scheifele et al. 2004 [24]

OralCDx® technique

6.4

Prospective

Department of Oral Surgery and Dental Radiology, Zentrum für Zahnmedizin, Campus Virchow, Charité--Universitätsmedizin Berlin

Germany

-

103

Sciubba 1999 [26]

OralCDx® technique

7.3

Prospective

Department of Dental Medicine, Long Island Jewish Medical Center

USA

U.S. Collaborative OralCDx® Study Group

945

Gupta et al. 2007 [26]

Oral brush biopsy

5.8

Prospective

Department of Pathology, Moti Lal Nehru Medical College, Allahabad University

India

-

96

Poate et al. 2004 [28]

Oral brush biopsy

7.5

Prospective

Oral Medicine, Division of Maxillofacial Diagnostic, Medical and Surgical Sciences, Eastman Dental Institute for Oral Health Care Sciences

UK

-

112

Weigum et al. 2010 [29]

Nanobiochip, exfoliative cytology

7.7

Prospective

Department of Dental Diagnostic Science, University of Texas Health Science Center

USA

National Institute for Dental and

Craniofacial Research

52

Jokerst et al. 2010 [31]

Nanobiochip

6.6

Prospective

Stanford University School of Medicine

USA

-

-

Wei et al. 2009 [32]

Saliva biomarkers

7.5

Prospective

University of California, Los Angeles School of Dentistry and Dental Research Institute

USA

NIH/National Institute of Dental and Craniofacial Research

-

Floriano et al. 2009 [33]

Saliva-based nanobiochip tests

7.6

Prospective

Department of Chemistry and Biochemistry, University of Texas

USA

National Institute of Dental and Craniofacial Research

41

Liu et al. 2009 [34]

Saliva biomarkers

7.5

Prospective

Department of Mechanical Engineering and Applied Mechanics,

USA

University of Pennsylvania Institute for Translational Medicine and Therapeutics

-

Zimmermann et al. 2007 [36]

Saliva biomarkers

7.8

Prospective

School of Dentistry and Dental Research Institute, University of California

USA

National Institute of Health

-

Xie et al. 2008 [37]

Saliva biomarkers

7

Prospective

Department of Biochemistry, Molecular Biology, and Biophysics, School of Dentistry, University of Minnesota

USA

-

-

Sugimoto et al. 2010 [39]

Saliva biomarkers

8

Prospective

UCLA Medical Center

USA

National Institute of Health

215

Hu et al. 2008 [41]

Saliva biomarkers

7.6

Prospective

Oral Biology and Medicine Division and Dental Research Institute, School of Dentistry, University of California

USA

U.S. Public Health Service

64

Rosin et al. 2000 [44]

Biomarkers; genetic

7.7

Prospective

British Columbia Cancer Agency/Cancer Research Centre

Canada

National Cancer Institute of Canada, Canadian Cancer Society

116

Boyle et al. 1993 [48]

Biomarkers; genetic

7.6

Prospective

Department of Oral Surgery, Johns Hopkins University

USA

-

102

Rosas et al. 2001 [50]

Biomarkers; genetic

7.9

Prospective

Department of Otolaryngology, Head and Neck Surgery, Johns Hopkins University School of Medicine

USA

National Institute of Dental and Craniofacial Research (NIH)

30

Chien et al. 1990 [52]

Biomarkers; genetic

7.5

Prospective

Department of Obstetrics and Gynaecology, First Affiliated Hospital, Human Medical University

China

-

92

Handschel et al. 2007 [54]

Biomarkers; genetic

6.9

Prospective

Department for Cranio- and Maxillofacial Surgery, Heinrich-Heine-University

Germany

-

-

Hasselmann et al. 2001 [55]

Saliva biomarkers; clinical chemistry

6.4

Prospective

Department of Dermatology, Saarland University Hospital

Germany

-

-

Ratajczak et al. 2006 [56]

Biomarkers; cellular

7.2

Prospective

James Graham Brown Cancer Center, University of Louisville

USA

Stem Cell Biology Program

-

García et al. 2008 [57]

Biomarkers; genetic

7.5

Prospective

Department of Medical Oncology, Hospital Universitario Puerta de Hierro

Spain

Ministerio de Educación y Ciencia and the Fundación de Investigación Médica Mutua Madrileña

-

Skog et al. 2008 [59]

Biomarkers; genetic

7.5

Prospective

Department of Neurology, Massachusetts General Hospital, and Neuroscience Program, Harvard Medical School

USA

Wenner-Gren Foundation Stiftelsen Olle Engkvist Byggmästare, Brain Tumor Society, and American Brain Tumor Association

-

Shpitzer et al. 2009 [63]

Saliva biomarkers

7.8

Prospective

Department of Otorhinolaryngology, Rabin Medical Center, Petah Tiqva and Sackler Faculty of Medicine

-

-

19

Vairaktaris et al. 2008 [64]

Saliva biomarkers

7.5

Prospective

Department of Oral and Maxillofacial Surgery, University of Athens Medical School, Attikon Hospital

Greece

-

152

St John et al. 2004 [64]

Saliva biomarkers

7.7

Prospective

School of Medicine, UCLA

USA

National Institutes of Health, UCLA Jonsson Cancer Center

32

Rhodus et al. 2005 [66]

Saliva biomarkers

7.6

Prospective

Department of Oral Medicine, University of Minnesota

USA

-

13

Arellano-Garcia et al. 2008 [67]

Saliva biomarkers

7.5

Prospective

School of Dentistry, Oral Biology and Medicine Division, Dental Research Institute, University of California

USA

U.S. Public Health Service

19

Betz et al. 2002 [111]

Optical biopsy

7.9

Prospective

Department of Oto-Rhino-Laryngology/Head and Neck Surgery, Ludwig Maximilians University

Germany

Wilhelm Sander Foundation

85

Leunig et al. 2000 [112]

Optical biopsy

7.5

Prospective

Department of Otorhinolaryngology--Head and Neck Surgery, University of Munich

Germany

Wilhelm Sander Foundation

8

Betz et al. 1999 [101]

Optical biopsy

7.7

Prospective

Department of Oto-Rhino-Laryngology/Head & Neck Surgery, Ludwig Maximilian University

Germany

Wilhelm Sander Foundation

49

Kulbersh et al. 2007 [103]

Optical biopsy

7.5

Prospective

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Alabama

USA

American Cancer Society, University of Alabama at Birmingham Comprehensive Cancer Center Core Grant NIH

33 Models

Ebenezar et al. 2012 [113]

Optical biopsy

7.3

Prospective

Anna University, Department of Medical Physics

India

-

25

Duraipandian et al. 2012 [118]

Optical biopsy

7.8

Prospective

National University of Singapore, Department of Bioengineering, Faculty of Engineering, Optical Bioimaging Laboratory

Singapore

National University of Singapore

2748

Guze et al. 2014 [133]

Optical biopsy

7.8

Prospective

Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Divisions of Oral Medicine, Dana-Farber Cancer Institute and Brigham and Women’s Hospital

USA

-

18

Krishnakumar et al. 2013 [125]

Optical biopsy

7.5

Prospective

Department of Physics, Annamalai University

India

-

-

Sahu et al. 2013 [126]

Optical biopsy

7

-

Chilakapati lab, ACTREC, Tata Memorial Centre

India

Advanced Centre for Treatment Research and Education in Cancer

70

Singh et al. 2013 [128]

Optical biopsy

7.3

Prospective

Chilakapati lab, ACTREC, Tata Memorial Centre

India

Advanced Centre for Treatment Research and Education in Cancer

84

Singh et al. 2012 [127]

Optical biopsy

7.5

Prospective

Advanced Centre for Treatment Research and Education in Cancer, Chilakapati Laboratory

India

Advanced Centre for Treatment Research and Education in Cancer

104 subjects

Deshmukh et al. 2011 [129]

Optical biopsy

7

Prospective

Chilakapati Laboratory

India

Advanced Center for Treatment Research and Education in Cancer

10

Oliveira et al. 2006 [130]

Optical biopsy

7.2

Prospective

Grupo de Optica Biomédica, Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba

Brazil

-

123 spectra

Malini et al. 2006 [131]

Optical biopsy

7.5

Prospective

Center for Laser Spectroscopy, Manipal Academy of Higher Education

India

Government of India

216 spectra

Krishna et al. 2004 [132]

Optical biopsy

6.8

Prospective

Center for Laser Spectroscopy, Manipal Academy of Higher Education

India

Government of India

-

Jerjes et al. 2004 [135]

Optical biopsy

7.5

Prospective

Department of Oral and Maxillofacial Surgery, University College London Hospitals

UK

Eastman Dental Institute, UCL, UCLH Head and Neck Centre

13

Sharwani et al. 2006 [140]

Optical biopsy

7.6

Prospective

Oral and Maxillofacial Surgery, Eastman Dental Institute

UK

Eastman Dental Institute, UCL, UCLH Head and Neck Centre, London, UK

25

Mourant et al. 2000 [137]

Optical biopsy

7

Prospective

Los Alamos National Laboratory, Bioscience Division

USA

-

-

Mourant et al. 1998 [138]

Optical biopsy

7.2

Prospective

Chemical Sciences and Technology Division, Los Alamos National Laboratory

USA

-

-

Lovat et al. 2006 [139]

Optical biopsy

7.8

Prospective

National Medical Laser Centre, Department of Surgery, Royal Free and University College Medical School, University College

UK

National Cancer Institute

181

A’Amar et al. 2013 [144]

Optical biopsy

7.5

Prospective

Department of Biomedical Engineering, Boston University

USA

-

42

Denkçeken et al. 2013 [145]

Optical biopsy

6.9

Prospective

Biomedical Optics Research Unit, Department of Biophysics, Faculty of Medicine, Akdeniz University

Turkey

Biomedical Optics Research Unit

10

Qi et al. 2012 [143]

Optical biopsy

7.7

Prospective

Department of Surgery and Cancer, Imperial College London

UK

ERC grant (China Scholarship Council)

-

Upile et al. 2012 [142]

Optical biopsy

7.8

Prospective

Head & Neck Unit, University College London Hospitals

UK

Eastman Dental Institute, UCL, UCLH Head and Neck Centre

73

Canpolat et al. 2012 [141]

Optical biopsy

7.6

Prospective

Department of Biophysics, School of Medicine, Akdeniz University

Turkey

-

28

Lau et al. 2009 [146]

Optical biopsy

7.9

Prospective

Massachusetts Institute of Technology, George R. Harrison Spectroscopy Laboratory

USA

National Institutes of Health

-

Müller et al. 2003 [136]

Optical biopsy

7.9

Prospective

Massachusetts Institute of Technology

USA

National Institutes of Health

91 tissue sites from 15 patients

Amelink et al. 2004 [147]

Optical biopsy

7.5

Prospective

Department of Radiation Oncology, Erasmus Medical Centre

The Netherlands

Dutch Technology Foundation STW, Applied Science Division of NWO and the Technology Program of the Ministry of Economic Affairs

-

Sterenborg et al. 2009 [148]

Study type(s) or biopsy

7.6

Prospective

Center for Optical Diagnostics and Therapy, Erasmus Medical Centre

The Netherlands

Dutch Technology Foundation STW, Applied Science Division of NWO and the Technology Program of the Ministry of Economic Affairs

21

de Visscher et al. 2012 [150]

Study type(s) or biopsy

7.5

Prospective

University Medical Centre Groningen, Department of Oral and Maxillofacial Surgery, Division of Oncology

The Netherlands

Dutch Technology Foundation STW, Applied Science Division of NWO and the Technology Program of the Ministry of Economic Affairs

54 male Wistar rats

Amelink et al. 2011 [149]

 

7.7

Prospective

Centre for Optical Diagnostics and Therapy, Department of Radiation Oncology, Erasmus Medical Centre

The Netherlands

Dutch Technology Foundation STW, Applied Science Division of NWO and the Technology Program of the Ministry of Economic Affairs

18

Karakullukcu et al. 2011 [151]

Study type(s) or biopsy

7.6

Prospective

The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Department of Head and Neck Oncology and Surgery

The Netherlands

Dutch Technology Foundation STW, Applied Science Division of NWO and the Technology Program of the Ministry of Economic Affairs

-

Kanick et al. 2008 [152]

Study type(s) or biopsy

7.5

Prospective

Erasmus Medical Centre, Department of Radiation Oncology, Centre for Optical Diagnostics and Therapy

The Netherlands

Dutch Technology Foundation STW, Applied Science Division of NWO and the Technology Program of the Ministry of Economic Affairs

-

Adalsteinsson et al. 1998 [174]

Study type(s) or biopsy

7.5

Prospective

Department of Radiology, Stanford University

USA

-

12

El-Sayed et al. 2002 [175]

Study type(s) or biopsy

7.8

Prospective

Cancer Care Manitoba

Canada

Cancer Care Manitoba

135

Maheshwari et al. 2000 [176]

Study type(s) or biopsy

7.6

Prospective

Department of Radiology, University of North Carolina

USA

University of North Carolina

37

Mukherji et al. 1997 [177]

Study type(s) or biopsy

7.8

Prospective

Department of Radiology, University of North Carolina School of Medicine

USA

-

49

Kunkel et al. 2003 [178]

Biochemical

7.8

Prospective

Department of Oral and Maxillofacial Surgery, University Hospital Mainz

Germany

-

118