Can saliva-based HPV tests establish cancer risk and guide patient management?

Source: Oral and Maxillofacial Pathology doi:10.1016 Author: Mark W. Lingen, DDS, PhD Section Editor, Oral and Maxillofacial Pathology Head and neck squamous cell carcinoma (HNSCC) is the 6th most common malignancy in the world today.1 Despite numerous advances in treatment, the 5-year survival rate has remained modest. This poor outcome is due to several factors, including delayed diagnosis. Therefore, improved early detection and effective prevention strategies are critical components for management of this malignancy. The etiology of classical HNSCC has been attributed to chronic exposure to tobacco and alcohol.2 In addition, there is now sufficient evidence to support the contention that high-risk forms of the human papillomavirus (HPV) are a major causative factor for HNSCC of the tonsil, base of tongue, and oropharynx.3-8 The increasing importance of HPV in oropharyngeal HNSCC has raised considerable concern and uncertainty among healthcare professionals and patients. For example, I am often asked to describe the clinical features of HPV-associated premalignant lesions. Unfortunately, to my knowledge, the clinical spectrum of HPV-associated premalignant disease has not been adequately described. Furthermore, because this subset of HNSCC often develops in hard to- examine locations, such as tonsillar crypts, it can be exceedingly difficult to even identify the carcinomas. In the absence of such information, how can clinicians identify patients that are at increased risk for harboring an HPV-associated premalignant lesions or HNSCC? Recently, a large commercial diagnostic lab began offering a saliva-based test for the identification of oral HPV infections. As a result of this new offering, I [...]

Epidermal growth factor receptor regulates beta-catenin location, stability, and transcriptional activity in oral cancer

Source: 7thspace.com/headlines Author: staff Many cancerous cells accumulate beta-catenin in the nucleus. We examined the role of epidermal growth factor receptor (EGFR) signaling in the accumulation of beta-catenin in the nuclei of oral cancer cells. Results: We used two strains of cultured oral cancer cells, one with reduced EGFR expression (OECM1 cells) and one with elevated EGFR expression (SAS cells), and measured downstream effects, such as phosphorylation of beta-catenin and GSK-3beta, association of beta-catenin with E-cadherin, and target gene regulation. We also studied the expression of EGFR, beta-catenin, and cyclin D1 in 112 samples of oral cancer by immunostaining. Activation of EGFR signaling increased the amount of beta-catenin in the nucleus and decreased the amount in the membranes. EGF treatment increased phosphorylation ofbeta-catenin (tyrosine) and GSK-3beta(Ser-9), resulting in a loss of beta-catenin association with E-cadherin. TOP-FLASH and FOP-FLASH reporter assays demonstrated that the EGFR signal regulates beta-catenin transcriptional activity and mediates cyclin D1 expression. Chromatin immunoprecipitation experiments indicated that the EGFR signal affects chromatin architecture at the regulatory element of cyclin D1, and that the CBP, HDAC1, and Suv39h1 histone/chromatin remodeling complex is involved in this process. Immunostaining showed a significant association between EGFR expression and aberrant accumulation of beta-catenin in oral cancer. Conclusions: EGFR signaling regulates beta-catenin localization and stability, target gene expression, and tumor progression in oral cancer. Moreover, our data suggest that aberrant accumulation of beta-catenin under EGFR activation is a malignancy marker of oral cancer. Author: Chien-Hsing LeeHsing-Wen HungPei-Hsin HungYi-Shing Shieh Source: Molecular Cancer 2010, 9:64

Absence Of CLP protein can be indicative of oral cancer

Source: www.sciencedaily.com Author: staff Human calmodulin-like protein (CLP) is found in many cell types including breast, thyroid, prostate, kidney, and skin. The protein can regulate many cell activities and has a highly specific expression. Gaining an understanding about the expression of CLP in oral epithelial cells and its possible downregulation (or lack of production) in cancer may be a potentially valuable marker in early detection of oral cancer. A new study in the Journal of Prosthodontics found that CLP is expressed in normal human oral muscosal cells and that downregulation of this protein may be an indicator of malignancy or cancer. Michael D. Brooks, DMD, MS, Richard D. Bennett, PhD, Emanuel E. Strehler, PhD, Thomas J. Sebo, MD, PhD, Stephen E. Eckert, DDS, MS, and Alan B. Carr, DMD, MS used a method of staining oral skin cells to see if they expressed this protein. A breast tissue sample that was known to have this protein was used as a basis for comparison. Normal cells in the mouth also possessed CLP. In malignancy or cancer, the same type of skin cells no longer expressed this protein. In the areas of cancerous cells, a decrease in CLP occurred. There was a sharp contrast in staining quality and clarity between benign and malignant tissue. In the majority of the cancerous regions, a complete lack of CLP was noted. This may be significant because calmodulin-like protein could be a marker for normal healthy oral cavity cells and diminished or complete loss of the [...]

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