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      Exciting new advances in oral cancer diagnosis: avenues to early detection

      review-article
      1 , , 2 , 3
      Head & Neck Oncology
      BioMed Central
      Oral Cancer, Diagnosis, Brush Biopsy, DNA, Saliva, Biomarkers, Spectroscopy

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          Abstract

          The prognosis for patients with oral squamous cell carcinoma remains poor in spite of advances in therapy of many other malignancies. Early diagnosis and treatment remains the key to improved patient survival. Because the scalpel biopsy for diagnosis is invasive and has potential morbidity, it is reserved for evaluating highly suspicious lesions and not for the majority of oral lesions which are clinically not suspicious. Furthermore, scalpel biopsy has significant interobserver and intraobserver variability in the histologic diagnosis of dysplasia. There is an urgent need to devise critical diagnostic tools for early detection of oral dysplasia and malignancy that are practical, noninvasive and can be easily performed in an out-patient set-up. Diagnostic tests for early detection include brush biopsy, toluidine blue staining, autofluorescence, salivary proteomics, DNA analysis, biomarkers and spectroscopy. This state of the art review critically examines these tests and assesses their value in identifying oral squamous cell carcinoma and its precursor lesions.

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          Most cited references49

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          Effect of screening on oral cancer mortality in Kerala, India: a cluster-randomised controlled trial.

          Oral cancer is common in men from developing countries, and is increased by tobacco and alcohol use. We aimed to assess the effect of visual screening on oral cancer mortality in a cluster-randomised controlled trial in India. Of the 13 clusters chosen for the study, seven were randomised to three rounds of oral visual inspection by trained health workers at 3-year intervals and six to a control group during 1996-2004, in Trivandrum district, Kerala, India. Healthy participants aged 35 years and older were eligible for the study. Screen-positive people were referred for clinical examination by doctors, biopsy, and treatment. Outcome measures were survival, case fatality, and oral cancer mortality. Oral cancer mortality in the study groups was analysed and compared by use of cluster analysis. Analysis was by intention to treat. Of the 96,517 eligible participants in the intervention group, 87,655 (91%) were screened at least once, 53,312 (55%) twice, and 29,102 (30%) three times. Of the 5145 individuals who screened positive, 3218 (63%) complied with referral. 95,356 eligible participants in the control group received standard care. 205 oral cancer cases and 77 oral cancer deaths were recorded in the intervention group compared with 158 cases and 87 deaths in the control group (mortality rate ratio 0.79 [95% CI 0.51-1.22]). 70 oral cancer deaths took place in users of tobacco or alcohol, or both, in the intervention group, compared with 85 in controls (0.66 [0.45-0.95]). The mortality rate ratio was 0.57 (0.35-0.93) in male tobacco or alcohol users and 0.78 (0.43-1.42) in female users. : Oral visual screening can reduce mortality in high-risk individuals and has the potential of preventing at least 37,000 oral cancer deaths worldwide.
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            Salivary transcriptome diagnostics for oral cancer detection.

            Oral fluid (saliva) meets the demand for noninvasive, accessible, and highly efficient diagnostic medium. Recent discovery that a large panel of human RNA can be reliably detected in saliva gives rise to a novel clinical approach, salivary transcriptome diagnostics. The purpose of this study is to evaluate the diagnostic value of this new approach by using oral squamous cell carcinoma (OSCC) as the proof-of-principle disease. Unstimulated saliva was collected from patients (n = 32) with primary T1/T2 OSCC and normal subjects (n = 32) with matched age, gender, and smoking history. RNA isolation was done from the saliva supernatant, followed by two-round linear amplification with T7 RNA polymerase. Human Genome U133A microarrays were applied for profiling human salivary transcriptome. The different gene expression patterns were analyzed by combining a t test comparison and a fold-change analysis on 10 matched cancer patients and controls. Quantitative polymerase chain reaction (qPCR) was used to validate the selected genes that showed significant difference (P < 0.01) by microarray. The predictive power of these salivary mRNA biomarkers was analyzed by receiver operating characteristic curve and classification models. Microarray analysis showed there are 1,679 genes exhibited significantly different expression level in saliva between cancer patients and controls (P < 0.05). Seven cancer-related mRNA biomarkers that exhibited at least a 3.5-fold elevation in OSCC saliva (P < 0.01) were consistently validated by qPCR on saliva samples from OSCC patients (n = 32) and controls (n = 32). These potential salivary RNA biomarkers are transcripts of IL8, IL1B, DUSP1, HA3, OAZ1, S100P, and SAT. The combinations of these biomarkers yielded sensitivity (91%) and specificity (91%) in distinguishing OSCC from the controls. The utility of salivary transcriptome diagnostics is successfully demonstrated in this study for oral cancer detection. This novel clinical approach could be exploited to a robust, high-throughput, and reproducible tool for early cancer detection. Salivary transcriptome profiling can be applied to evaluate its usefulness for other major disease applications as well as for normal health surveillance.
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              Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value.

              Several recent studies have indicated that cells at the invasive tumour margins often are different from cells within other parts of various human cancers. In this work, we have studied all squamous cell carcinomas of the floor of the mouth registered in Norway during the years 1963-1972 (N = 96). Borderline cases and cases given no treatment were excluded. Of the remaining 79 cases, biopsy specimens acceptable for histological grading were obtained from 61 patients. Only the most invasive margins of the tumours were histologically graded independently by two pathologists according to a multifactorial grading system. The results confirmed our previous findings that grading of invasive tumour margins is an independent prognostic factor in Cox's multivariate survival analysis (P less than 0.01). Inter-observer agreement was calculated by kappa statistics, and good agreement was obtained (kappa = 0.63). Neither agreement nor prognostic value was improved after calibration of the pathologists. Conventional Borders' grading of the whole biopsy had no prognostic value (P less than 0.38). We conclude that invasive cell grading may be of value for treatment planning of oral cancers, and that further studies of the deep, invasive parts of oral and other cancers are needed in order to obtain a better understanding of tumour cell invasion and metastasis.
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                Author and article information

                Journal
                Head Neck Oncol
                Head & Neck Oncology
                BioMed Central
                1758-3284
                2011
                28 July 2011
                : 3
                : 33
                Affiliations
                [1 ]Department of Pathology, Moti Lal Nehru Medical College, Lowther Road Allahabad, 211001 India
                [2 ]Department of Biochemistry and Coordinator-Chair, Center of Bioinformatics, University of Allahabad, Allahabad, 211001 India
                [3 ]Present Address: Department of Biochemistry, University of Bologna, Italy
                Article
                1758-3284-3-33
                10.1186/1758-3284-3-33
                3170277
                21798030
                4cf29268-f659-40c2-871c-3685cb9b5513
                Copyright ©2011 Mehrotra and Gupta; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 July 2011
                : 28 July 2011
                Categories
                Review

                Oncology & Radiotherapy
                spectroscopy,oral cancer,diagnosis,dna,biomarkers,brush biopsy,saliva
                Oncology & Radiotherapy
                spectroscopy, oral cancer, diagnosis, dna, biomarkers, brush biopsy, saliva

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