ABSTRACT
BACKGROUND: A large number of oral squamous cell carcinomas (OSCCs) are believed to be preceded by oral potentially malignant disorders (OPMD) that have an increased likelihood of malignant transformation compared to clinically normal mucosa. This study was performed to identify differentially expressed genes between OPMDs that underwent malignant transformation (MT) and those that did not, termed "non-transforming" (NT) cases. METHODS: Total RNA was extracted from formalin-fixed paraffin-embedded tissue biopsies of 20 OPMD cases with known clinical outcomes (10 MT vs. 10 NT). Samples were assessed for quantity, quality and integrity of RNA prior to sequencing. Analysis for differential gene expression between MT and NT was performed using statistical packages in R. Genes were considered to be significantly differentially expressed if the False Discovery Rate corrected P-value was < 0.05. RESULTS: RNA yield was variable but RNA purity was good (A260/A280 > 1.90). Analysis of RNA-Sequencing outputs revealed 41 genes (34 protein-coding; 7 non-coding) that were significantly differentially expressed between MT and NT cases. The log2 fold change for the statistically significant differentially expressed genes ranged from -2.63 to 2.48, with 23 protein-coding genes being downregulated and 11 protein-coding genes being upregulated in MT cases compared to NT cases. CONCLUSION: Several candidate genes that may play a role in malignant transformation of OPMD have been identified. Experiments to validate these candidates are underway. It is anticipated that this work will contribute to better understanding of the etiopathogenesis of OPMD and development of novel biomarkers.
Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Biopsy , Carcinoma, Squamous Cell/genetics , Cell Transformation, Neoplastic/genetics , Gene Expression , Humans , Mouth Neoplasms/geneticsABSTRACT
PURPOSE: Diagnostic tonsillectomy is rarely an oncologic operation owing to close or positive margins. The standard of care is for further treatment to the primary site, typically with adjuvant radiotherapy. METHODS: 14 patients with close or positive margins following a diagnostic tonsillectomy underwent transoral robotic surgery (TORS) and lateral oropharyngectomy; five patients with the longest follow-up had their excision specimens examined with a step serial sectioning technique (SSS). RESULTS: Conventional histopathological examination of the TORS resection specimens did not demonstrate residual carcinoma in 13 patients, confirmed by examination using SSS in 5 patients. There were no post-operative complications or long-term functional deficit. Seven patients received surgery alone with 100% overall and disease specific survival, respectively (median follow-up 27.5 months; range 5.2-50.4). CONCLUSIONS: This prospective study suggests that TORS lateral oropharyngectomy alone is an oncologically safe treatment when close or positive margins are identified on diagnostic tonsillectomy in HPV-positive SCC.
Subject(s)
Carcinoma, Squamous Cell/surgery , Oropharyngeal Neoplasms/surgery , Papillomavirus Infections/pathology , Pharyngectomy , Robotic Surgical Procedures , Tonsillectomy , Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Epithelial Cells/pathology , Female , Humans , Male , Margins of Excision , Middle Aged , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/virology , Papillomavirus Infections/complications , Prospective Studies , Radiotherapy, AdjuvantABSTRACT
BACKGROUND: Osteoradionecrosis of the jaw (ORNJ) is a well-recognized complication of radiotherapy. The purpose of this study was to assess predictive factors for the development of ORNJ. METHODS: A retrospective study of 325 patients with head and neck squamous cell carcinoma (HNSCC) treated at one institution between January 1, 1999, and December 31, 2008, was conducted. Outcome measure was the presence/absence of ORNJ. Time to event was recorded and Cox proportional hazard regression analysis was used to determine statistically significant predictive factors. RESULTS: Fifty-nine patients had ORNJ. Statistical analysis using Cox regression analysis identified several statistically significant variables: dentoalveolar surgery; peri-resective surgery of the jaw; continued tobacco usage after radiotherapy, diabetes mellitus type 2 (DM2); and total radiation dose. CONCLUSION: Patients at greater risk of developing ORNJ can be identified and measures can be instituted to reduce its incidence and expedite management when it does occur.