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