Cross validated serum small extracellular vesicle microRNAs for the detection of oropharyngeal squamous cell carcinoma.

BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is often diagnosed at an advanced stage because the disease often causes minimal symptoms other than metastasis to neck lymph nodes. Better tools are required to assist with the early detection of OPSCC. MicroRNAs (miRNAs, miRs) are potential biomarkers for early head and neck squamous cell cancer diagnosis, prognosis, recurrence, and presence of metastatic disease. However, there is no widespread agreement on a panel of miRNAs with clinically meaningful utility for head and neck squamous cell cancers. This could be due to variations in the collection, storage, pre-processing, and isolation of RNA, but several reports have indicated that the selection and reproducibility of biomarkers has been widely affected by the methods used for data analysis. The primary analysis issues appear to be model overfitting and the incorrect application of statistical techniques. The purpose of this study was to develop a robust statistical approach to identify a miRNA signature that can distinguish controls and patients with inflammatory disease from patients with human papilloma virus positive (HPV +) OPSCC. METHODS: Small extracellular vesicles were harvested from the serum of 20 control patients, 20 patients with gastroesophageal reflux disease (GORD), and 40 patients with locally advanced HPV + OPSCC. MicroRNAs were purified, and expression profiled on OpenArray™. A novel cross validation method, using lasso regression, was developed to stabilise selection of miRNAs for inclusion in a prediction model. The method, named StaVarSel (for Stable Variable Selection), was used to derive a diagnostic biomarker signature. RESULTS: A standard cross validation approach was unable to produce a biomarker signature with good cross validated predictive capacity. In contrast, StaVarSel produced a regression model containing 11 miRNA ratios with potential clinical utility. Sample permutations indicated that the estimated cross validated prediction accuracy of the 11-miR-ratio model was not due to chance alone. CONCLUSIONS: We developed a novel method, StaVarSel, that was able to identify a panel of miRNAs, present in small extracellular vesicles derived from blood serum, that robustly cross validated as a biomarker for the detection of HPV + OPSCC. This approach could be used to derive diagnostic biomarkers of other head and neck cancers.

Reviewing indications for panendoscopy in the investigation of head and neck squamous cell carcinoma.

BACKGROUND: The role of panendoscopy in the modern investigation of head and neck cancer is changing with the development of improved radiological techniques, in-office biopsy capabilities and the low rate of synchronous primary tumours. This study aimed to review the indications for panendoscopy in the investigation of newly diagnosed head and neck cancer. METHOD: A retrospective review was conducted of 186 patients with newly diagnosed head and neck cancer, between January 2014 and December 2015, at two tertiary centres. RESULTS: Obtaining a tissue diagnosis was the most common indication for panendoscopy (65 per cent), followed by surgical planning including transoral robotic surgery suitability assessment (22.6 per cent), and the investigation of carcinoma of an unknown primary (11.3 per cent). Two synchronous primary tumours were identified, generating a yield of 1.1 per cent. CONCLUSION: Panendoscopy remains integral in the assessment of transoral robotic surgery suitability. Refining indications for modern panendoscopy could reduce the need for this procedure in this cohort of patients.

A systematic review of validated sinus surgery simulators.

BACKGROUND: Simulation provides a safe and effective opportunity to develop surgical skills. A variety of endoscopic sinus surgery (ESS) simulators has been described in the literature. Validation of these simulators allows for effective utilisation in training. OBJECTIVE OF REVIEW: To conduct a systematic review of the published literature to analyse the evidence for validated ESS simulation. SEARCH STRATEGY: Pubmed, Embase, Cochrane and Cinahl were searched from inception of the databases to 11 January 2017. EVALUATION METHOD: Twelve thousand five hundred and sixteen articles were retrieved of which 10 112 were screened following the removal of duplicates. Thirty-eight full-text articles were reviewed after meeting search criteria. Evidence of face, content, construct, discriminant and predictive validity was extracted. RESULTS: Twenty articles were included in the analysis describing 12 ESS simulators. Eleven of these simulators had undergone validation: 3 virtual reality, 7 physical bench models and 1 cadaveric simulator. Seven of the simulators were shown to have face validity, 7 had construct validity and 1 had predictive validity. None of the simulators demonstrated discriminate validity. CONCLUSION: This systematic review demonstrates that a number of ESS simulators have been comprehensively validated. Many of the validation processes, however, lack standardisation in outcome reporting, thus limiting a meta-analysis comparison between simulators.

Validation of virtual-reality-based simulations for endoscopic sinus surgery.

BACKGROUND: Virtual reality (VR) simulators provide an alternative to real patients for practicing surgical skills but require validation to ensure accuracy. Here, we validate the use of a virtual reality sinus surgery simulator with haptic feedback for training in Otorhinolaryngology - Head & Neck Surgery (OHNS). METHODS: Participants were recruited from final-year medical students, interns, resident medical officers (RMOs), OHNS registrars and consultants. All participants completed an online questionnaire after performing four separate simulation tasks. These were then used to assess face, content and construct validity. anova with post hoc correlation was used for statistical analysis. RESULTS: The following groups were compared: (i) medical students/interns, (ii) RMOs, (iii) registrars and (iv) consultants. Face validity results had a statistically significant (P < 0.05) difference between the consultant group and others, while there was no significant difference between medical student/intern and RMOs. Variability within groups was not significant. Content validity results based on consultant scoring and comments indicated that the simulations need further development in several areas to be effective for registrar-level teaching. However, students, interns and RMOs indicated that the simulations provide a useful tool for learning OHNS-related anatomy and as an introduction to ENT-specific procedures. CONCLUSIONS: The VR simulations have been validated for teaching sinus anatomy and nasendoscopy to medical students, interns and RMOs. However, they require further development before they can be regarded as a valid tool for more advanced surgical training.