Charles S. Coffey

Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss

Head and neck squamous cell carcinoma (HNSCC) is characterized by aggressive behavior with a propensity for metastasis and recurrence. Here we report a comprehensive analysis of the molecular and clinical features of HNSCC that govern patient survival. We find that TP53 mutation is frequently accompanied by loss of chromosome 3p and that the combination of these events is associated with a surprising decrease in survival time (1.9 years versus >5 years for TP53 mutation alone). The TP53-3p interaction is specific to chromosome 3p and validates in HNSCC and pan-cancer cohorts. In human papillomavirus (HPV)-positive tumors, in which HPV inactivates TP53, 3p deletion is also common and is associated with poor outcomes. The TP53-3p event is modified by mir-548k expression, which decreases survival further, and is mutually exclusive with mutations affecting RAS signaling. Together, the identified markers underscore the molecular heterogeneity of HNSCC and enable a new multi-tiered classification of this disease.

Lymph Node Yield as a Predictor of Survival in Pathologically Node Negative Oral Cavity Carcinoma.

Objective Even after a pathologically node-negative (pN0) neck dissection for oral cavity squamous cell carcinoma (SCC), patients may develop regional recurrence. In this study, we (1) hypothesize that an increased number of lymph nodes removed (lymph node yield) in patients with pN0 oral SCC predicts improved survival and (2) explore predictors of survival in these patients using a multivariable model. Study Design Case series with chart review. Setting Administrative database analysis. Subjects and Methods The SEER database was queried for patients diagnosed with all-stage oral cavity SCC between 1988 and 2009 who were determined to be pN0 after elective lymph node dissection. Demographic and treatment variables were extracted. The association of lymph node yield with 5-year all-cause survival was studied with multivariable survival analyses. Results A total of 4341 patients with pN0 oral SCC were included in this study. The 2 highest lymph node yield quartiles (representing >22 nodes removed) were found to be significant predictors of overall survival (22-35 nodes: hazard ratio [HR] = 0.854, P = .031; 36-98 nodes: HR = 0.827, P = .010). Each additional lymph node removed during neck dissection was associated with increased survival (HR = 0.995, P = .022). Conclusion These data suggest that patients with oral SCC undergoing elective neck dissection may experience an overall survival benefit associated with greater lymph node yield. Mechanisms behind the demonstrated survival advantage are unknown. Larger nodal dissections may remove a greater burden of microscopic metastatic disease, diminishing the likelihood of recurrence. Lymph node yield may serve as an objective measure of the adequacy of lymphadenectomy.

Rising incidence of oral tongue cancer among white men and women in the United States, 1973–2012

BACKGROUND Despite significant reductions in tobacco use in the US, oral tongue cancer incidence has reportedly increased in recent years, particularly in young white women. We conducted age-period-cohort analyses to identify birth cohorts that have experienced increased oral tongue cancer incidence, and compared these with trends for oropharyngeal cancer, a cancer caused by human papillomavirus (HPV) that has also recently increased. METHODS We utilized cancer incidence data (1973-2012) from 18 registries maintained by the NCI SEER Program. Incidence trends were evaluated using log-linear joinpoint regression and age-period-cohort modeling was utilized to simultaneously evaluate effects of age, calendar year, and birth year on incidence trends. RESULTS Incidence of oral tongue cancer increased significantly among white women during 1973-2012 (0.6% annual increase, p<0.001) and white men during 2008-2012 (5.1% annual increase, p=0.004). The increase was most apparent among younger white individuals (<50years; annual increase of 0.7% for men [p=0.02] and 1.7% for women [p<0.001] during 1973-2012). Furthermore, the magnitude of the increase during 1973-2012 was similar between young white men and women (2.3 vs. 1.8 cases per million, respectively). Incidence trends for oropharyngeal cancer were similar to trends for oral tongue cancer and similar birth cohorts (born after the 1940s) experienced rising incidence of these cancers (p-value: white men=0.12, white women=0.42), although the magnitude of increase was greater for oropharyngeal cancer. CONCLUSIONS The incidence of oral tongue and oropharyngeal cancer has significantly increased among young white men and women within the same birth cohorts in the US.

Chronic Opioid Use Following Surgery for Oral Cavity Cancer

Importance Opioid misuse and overuse has become an epidemic. Chronic opioid use among oral cavity cancer patients after surgery has not been described. Objectives To assess the prevalence of chronic opioid use in patients undergoing surgery for oral cavity cancer, and evaluate possible associated clinical factors; and the association between opioid use and survival. Design, Setting, and Participants For this retrospective cohort study of patients undergoing surgery for oral cavity cancer a consecutive sample of 99 patients between January 1, 2011, and September 30, 2016, were identified through the institutional cancer registry from a single academic center. Exposures Surgery for oral cavity cancer. Main Outcomes and Measures Chronic opioid use, defined as more than 90 days from surgery. Factors associated with chronic opioid use were investigated by univariable and multivariable logistic regression. The Kaplan-Meier method and Cox proportional hazards model were used to assess overall survival and disease-free survival. Results The mean (SD) patient age was 62.6 (14.3) years; 60 patients (60%) were male. Chronic opioid use was observed in 41 patients (41%). On multivariable logistic regression, preoperative opioid use (odds ratio [OR], 5.6; 95% CI, 2.2-14.3), tobacco use (OR, 2.8; 95% CI, 1.0-8.0), and development of persistence, recurrence, or a second primary tumor (OR, 2.8; 95% CI, 1.0-7.4) were associated with chronic opioid use. Among preoperative opioid users, estimated overall survival (hazard ratio [HR], 3.2; 95% CI, 1.4-7.1) was decreased, and chronic opioid use was associated with decreased disease-free survival (HR, 2.7; 95% CI, 1.1-6.6). Conclusions and Relevance In patients undergoing surgery for oral cavity tumors, the prevalence of chronic opioid use was considerable. Preoperative opioid use, tobacco use, and development of persistence, recurrence, or a second primary tumor were associated with chronic opioid use after surgery, and both preoperative and chronic opioid use were associated with decreased survival.

Mucosal expression of nerve growth factor and brain-derived neurotrophic factor in chronic rhinosinusitis.

Background Allergic rhinitis (AR) is characterized in part by hyperresponsiveness to nonspecific stimuli, a phenomenon that reflects the fundamental role of nasal neural pathways in chronic airway inflammation. Neurotrophins may serve pivotal roles in mediating hyperresponsiveness in allergic airway disease, although the role of such neurogenic mediators in chronic rhinosinusitis (CRS) is not well understood. This study was designed to examine the expression of two potent neurotrophins, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), in CRS. Methods Inferior turbinate and sinus mucosa were obtained from CRS patients with and without nasal polyps (NPs) and from nonallergic controls. Enzyme-linked immunosorbent assay was used for quantitative determination of tissue concentrations of NGF and BDNF. Results Ninety-four tissue samples from 48 patients were included. Mean concentration of NGF in sinus mucosa was significantly higher in CRS than controls. CRS without NPs was associated with a 60% increase in sinus NGF over controls (p < 0.05), and CRS with NPs was associated with a 140% increase (p < 0.05). Mean sinus NGF concentration was significantly elevated in allergic subjects compared with controls (p < 0.01). A similar trend was noted in subjects with nonallergic CRS, although this did not reach significance. Mean BDNF concentration was decreased in CRS compared with controls, with the most significant decrease in patients with polyps (p < 0.05). Mean turbinate concentration of both NGF and BDNF were similar in controls and CRS. Conclusion Increased expression of NGF may contribute to neural hyperresponsiveness in CRS sinus mucosa, particularly those patients with NP and/or allergies. BDNF expression is decreased in CRS sinus mucosa. Alterations in neurogenic inflammation may contribute to the pathophysiology of CRS and provide alternative therapeutic targets.

Predictors of high-risk and low-risk oral HPV infection in the United States

Determine predictors of high‐risk and low‐risk oral HPV infection in the United States.

Cost-Effectiveness Analysis of Elective Neck Dissection in Patients With Clinically Node-Negative Oral Cavity Cancer

Purpose Recently, a large randomized trial found a survival advantage among patients who received elective neck dissection in conjunction with primary surgery for clinically node-negative oral cavity cancer compared with those receiving primary surgery alone. However, elective neck dissection comes with greater upfront cost and patient morbidity. We present a cost-effectiveness analysis of elective neck dissection for the initial surgical management of early-stage oral cavity cancer. Methods We constructed a Markov model to simulate primary, adjuvant, and salvage therapy; disease recurrence; and survival in patients with T1/T2 clinically node-negative oral cavity squamous cell carcinoma. Transition probabilities were derived from clinical trial data; costs (in 2015 US dollars) and health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollar per quality-adjusted life-year (QALY), were calculated with incremental cost-effectiveness ratios less than

Esophageal dilation in head and neck cancer patients: A systematic review and meta‐analysis

100,000/QALY considered cost effective. We conducted one-way and probabilistic sensitivity analyses to examine model uncertainty. Results Our base-case model found that over a lifetime the addition of elective neck dissection to primary surgery reduced overall costs by

A rare case of exclusively oncocytic mucoepidermoid carcinoma with MAML2 translocation

6,000 and improved effectiveness by 0.42 QALYs compared with primary surgery alone. The decrease in overall cost despite the added neck dissection was a result of less use of salvage therapy. On one-way sensitivity analysis, the model was most sensitive to assumptions about disease recurrence, survival, and the health utility reduction from a neck dissection. Probabilistic sensitivity analysis found that treatment with elective neck dissection was cost effective 76% of the time at a willingness-to-pay threshold of

Concordant Oral and Vaginal Human Papillomavirus Infection in the United States.

100,000/QALY. Conclusion Our study found that the addition of elective neck dissection reduces costs and improves health outcomes, making this a cost-effective treatment strategy for patients with early-stage oral cavity cancer.