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


      , 1 , 2 , 3

      Head & Neck Oncology

      BioMed Central

      Oral Cancer, Diagnosis, Brush Biopsy, DNA, Saliva, Biomarkers, Spectroscopy

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          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 references 49

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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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              Oral cancer diagnosis by mechanical phenotyping.

              Oral squamous cell carcinomas are among the 10 most common cancers and have a 50% lethality rate after 5 years. Despite easy access to the oral cavity for cancer screening, the main limitations to successful treatment are uncertain prognostic criteria for (pre-)malignant lesions. Identifying a functional cellular marker may represent a significant improvement for diagnosis and treatment. Toward this goal, mechanical phenotyping of individual cells is a novel approach to detect cytoskeletal changes, which are diagnostic for malignant change. The compliance of cells from cell lines and primary samples of healthy donors and cancer patients was measured using a microfluidic optical stretcher. Cancer cells showed significantly different mechanical behavior, with a higher mean deformability and increased variance. Cancer cells (n approximately 30 cells measured from each patient) were on average 3.5 times more compliant than those of healthy donors [D(normal) = (4.43 +/- 0.68) 10(-3) Pa(-1); D(cancer) = (15.8 +/- 1.5) 10(-3) Pa(-1); P < 0.01]. The diagnosis results of the patient samples were confirmed by standard histopathology. The generality of these findings was supported by measurements of two normal and four cancer oral epithelial cell lines. Our results indicate that mechanical phenotyping is a sensible, label-free approach for classifying cancer cells to enable broad screening of suspicious lesions in the oral cavity. It could in principle be applied to any cancer to aid conventional diagnostic procedures.

                Author and article information

                Head Neck Oncol
                Head & Neck Oncology
                BioMed Central
                28 July 2011
                : 3
                : 33
                [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
                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.


                Oncology & Radiotherapy

                spectroscopy, oral cancer, diagnosis, dna, biomarkers, brush biopsy, saliva


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