BACKGROUND Human papillomavirus (HPV) is a well-established prognostic marker for oropharyngeal squamous cell cancer (OPSCC). Because of the limited numbers of women and nonwhites in studies to date, sex and racial/ethnic differences in prognosis have not been well explored. In this study, survival differences were explored by the tumor HPV status among 1) patients with OPSCCs by sex and race and 2) patients with nonoropharyngeal (non-OP) head and neck squamous cell cancers (HNSCCs). METHODS This retrospective, multi-institution study included OPSCCs and non-OP HNSCCs of the oral cavity, larynx, and nasopharynx diagnosed from 1995 to 2012. Race/ethnicity was categorized as white non-Hispanic, black non-Hispanic, Asian non-Hispanic, and Hispanic of any race. Tumors were centrally tested for p16 overexpression and the presence of HPV by HPV16 DNA and high-risk HPV E6/E7 messenger RNA in situ hybridization. Kaplan-Meier and Cox proportional hazards models were used to evaluate overall survival (OS). RESULTS The study population included 239 patients with OPSCC and 621 patients with non-OP HNSCC with a median follow-up time of 3.5 years. After adjustments for the tumor HPV status, age, current tobacco use, and stage, the risk of death was lower for women versus men with OPSCC (adjusted hazard ratio, 0.55; P =.04). The results were similar with p16. In contrast, for non-OP HNSCCs, HPV positivity, p16 positivity, and sex were not associated with OS. CONCLUSIONS For OPSCC, there are differences in survival by sex, even after the tumor HPV status has been taken into account. For non-OP HNSCC, the HPV status and the p16 status are not of prognostic significance.

The ESS is a major determinant of HR-QoL and should be considered as a measurement of treatment efficacy in HHT-related epistaxis.

Objective/Purpose Laryngotracheal stenosis (LTS) is a chronic fibrotic disease characterized by fibroblast proliferation, collagen deposition, and matrix remodeling in the lamina propria of the larynx and/or trachea. Current medical therapies are limited by a poor understanding of the effector cell’s (fibroblasts) cellular biology and metabolism. The purpose of this study is to compare cellular proliferation, function, and metabolism between normal and LTS-derived fibroblasts in vitro. Methods Human biopsies of normal and iatrogenic LTS tissue (n=7) were obtained and fibroblasts were isolated and cultured in vitro. Cellular proliferation, cellular histology, gene expression and metabolic analyses were performed. Statistical analyses comparing normal and scar-derived fibroblasts were performed. Results LTS fibroblast proliferation rate, cellular surface area, and collagen-1 expression were increased compared to normal fibroblasts. Cellular metabolic analysis of LTS-derived fibroblasts demonstrated reduced oxidative phosphorylation and increased glycolysis/oxidative phosphorylation ratio compared with normal fibroblasts. Conclusion Human iatrogenic LTS-derived fibroblasts demonstrated aberrant behavior when compared with normal fibroblasts. A Warburg-like effect was revealed suggesting human iatrogenic LTS fibroblasts drive their proliferation with aerobic glycolysis. The distinct metabolism suggests metabolic inhibitors could reduce fibroblast hyperplasia and hypertrophy in LTS and fibrosis in general.

4. Laryngoscope, 126:1029-1032, 2016.

4. Laryngoscope, 128:398-402, 2018.

Objectives 1) Develop a novel method for serial assessment of gene and protein expression in laryngotracheal stenosis (LTS) 2) Assess cytokine expression and determine an immunophenotype in LTS. Study Design A matched comparison of endolaryngeal brush-biopsy samples from laryngotracheal scar and normal airway. Setting Tertiary care hospital, 2015–2016 Methods Brush-biopsy specimens of laryngotracheal scar and normal trachea were obtained from seventeen LTS patients at the time of OR dilation and were used for protein and RNA extraction. Gene expression of the TH1 cytokine Interferon-ϒ (INF-ϒ), TH2 cytokine Interleukin (IL) – 4, Transforming Growth Factor – β, and Collagen-1 (Coll1) was quantified using quantitative RT-PCR. Cytokine analysis was performed with flow cytometry using a cytometric bead array. Results LTS specimens demonstrated a 13.68 fold increase in Coll1 gene expression compared to normal (p<0.001, n=17). Additionally, IL-4 gene expression showed a 3.76-fold increase (p<0.001, n=17) in LTS scar. When stratified into iatrogenic LTS (iLTS) and idiopathic subglottic stenosis (iSGS) cohorts INF-ϒ gene expression was significantly increased in iSGS (p=0.011). Soluble cytokine measurements were below the limit of detection for reliable quantification and thus could not be assessed. Conclusions Brush biopsies from LTS samples can be successfully utilized for RNA extraction and demonstrate the expected increase in Coll1 gene expression associated with LTS. Preliminary gene expression suggests abnormal collagen production may be mediated by the TH2 cytokine IL-4, and that increased INF-ϒ expression may represent a key difference between iLTS and iSGS. Further analysis of soluble cytokines is needed to confirm these findings.

Objectives Determine the effect of endoscopic skull base surgery (ESBS) on long‐term olfactory outcomes after surgery. Methods An English‐language search was conducted using the Cochrane, MEDLINE, Scopus, and Embase databases from January 2000 to October 2017 for adult patients undergoing ESBS with subjective and objective olfaction outcomes. Two authors independently examined articles to identify those meeting inclusion criteria. Studies examining objective olfactory outcomes after ESBS were included in the meta‐analysis. A random‐effects meta‐analysis of patients undergoing sellar and parasellar ESBS was conducted to compare preoperative and postoperative olfactory outcomes using the University of Pennsylvania Smell Identification Test (UPSIT) and Cross‐Cultural Smell Identification Test (CCSIT). Results Among 339 eligible articles, 29 articles met inclusion criteria. Twenty‐five of these focused on sellar and parasellar tumors. Individual articles not meeting criteria for meta‐analysis were qualitatively reported. Meta‐analysis showed there was no difference in preoperative and postoperative olfactory function after sellar and parasellar ESBS based on the UPSIT (five studies, mean difference [MD] = −1.03; 95% CI: −3.98, 1.93; P = .50) and the CCIST (three studies, MD = −0.77; 95% CI: −3.03, 1.49; P = .50). A pooled overall meta‐analysis revealed similar results (eight studies, effect size = −0.30; 95% CI: −0.79, 0.18; P = .22). However, heterogeneity for all meta‐analyses was high (I2 > 95%, P < .01), suggesting significant variation in the included studies. Conclusions Based on published objective olfaction outcomes after sellar and parasellar ESBS, there was no significant difference between preoperative and postoperative olfaction. Further prospective studies using validated objective measures of olfaction are required to improve our understanding on this subject. Level of Evidence 2a Laryngoscope, 129:1998–2007, 2019

The current analysis provides external validation for both staging systems in an independent and heterogeneously treated patient population. Although the MDACC staging system is an improvement over the AJCC-7ed, the ICON-S stage provides superior stratification of overall and progression-free survival, thereby supporting its use as the updated AJCC staging system for OPC. Cancer 2017;123:1768-1777. © 2017 American Cancer Society.