Purpose: The goal of this study was to examine the effect of tobacco use on disease recurrence (local/ regional recurrence, distant metastasis, or second primary) among patients with human papillomavirus (HPV)-positive squamous cell carcinoma of the oropharynx (SCCOP) following a complete response to chemoradiation therapy.Experimental Design: Between 1999 and 2007, 124 patients with advanced SCCOP (86% with stage IV) and adequate tumor tissue for HPV analysis who were enrolled in one of two consecutive University of Michigan treatment protocols were prospectively included in this study. Patients were categorized as never-, former, or current tobacco users. The primary end points were risk of disease recurrence and time to recurrence; secondary end points were disease-specific survival and overall survival.Results: One hundred and two patients (82.3%) had HPV-positive tumors. Over two thirds (68%) of patients with HPV-positive tumors were tobacco users. Among HPV-positive patients, current tobacco users were at significantly higher risk of disease recurrence than never-tobacco users (hazard ratio, 5.2; confidence interval, 1.1-24.4; P = 0.038). Thirty-five percent of HPV-positive ever tobacco users recurred compared with only 6% of HPV-positive never users and 50% of HPV-negative patients. All HPV-negative patients were tobacco users and had significantly shorter times to recurrence (P = 0.002), and had reduced disease-specific survival (P = 0.004) and overall survival (P < 0.001) compared with HPV-positive patients. Compared with HPV-positive never-tobacco users, those with a tobacco history showed a trend for reduced disease-specific survival (P = 0.064) but not overall survival (P = 0.221).Conclusions: Current tobacco users with advanced, HPV-positive SCCOP are at higher risk of disease recurrence compared with never-tobacco users. Clin Cancer Res; 16(4); 1226-35. ©2010 AACR.Head and neck squamous cell carcinoma is the eighth most common malignancy worldwide (1) and represents ∼5% of new cancer diagnoses worldwide annually (2). Over the past three decades, there has been a steady increase in the incidence of tonsil and tongue squamous cell carcinomas (3, 4). Recent evidence has identified high-risk human papillomavirus (HPV), particularly HPV-16, as a causative agent for a subset of head and neck squamous cell carcinomas, accounting for over 50% of squamous cell carcinomas of the oropharynx (SCCOP) in the United States (5-9). HPV-positive SCCOP has a distinct risk factor profile (6) and oncogenic mechanism (10, 11), and likely portends a more favorable prognosis than HPV-negative SCCOP (5,7,(12)(13)(14)(15)(16)(17). Despite its effect on prognosis, tumor HPV status has not yet been used to alter therapeutic management. The most popular current treatment for advanced SCCOP, regardless of HPV status, involves concurrent chemoradiation Authors' Affiliations:

Objective To determine whether baseline hearing loss increases cognitive decline and risk for all-cause dementia in a population of elderly individuals. Study design Longitudinal cohort study Setting Community-based, outpatient Patients Men and women aged 65 years or older without dementia at baseline Intervention(s) All subjects completed the Modified Mini-Mental Status Exam (3MS-R) at baseline and over 3 triennial follow-up visits. Hearing loss (HL) at baseline was based on observation of hearing difficulties during testing or interview. Incident dementia was determined by clinical assessment and expert consensus. Main outcome measure(s) Dementia and 3MS-R score. Results At baseline 4,463 subjects were without dementia, 836 of whom had HL. Of those with HL, 16.3% developed dementia, compared to 12.1% of those without HL (p<0.001). Mean time to dementia was 10.3 years in the HL group vs. 11.9 years for non-HL (Log Rank test p<0.001). In Cox regression analyses controlling for gender, presence of APOE- ε4 allele, education, and baseline age, and cardiovascular risk factors, HL was an independent predictor of developing dementia (Hazard ratio = 1.27, p=0.026 (95% CI = 1.03, 1.56). Linear mixed models controlling for similar covariates showed HL was associated with faster decline on the 3MS-R, at a rate of 0.26 points/year worse than those without HL. Conclusions Elderly individuals with HL have an increased rate of developing dementia and more rapid decline on 3MS-R scores than their non-hearing impaired counterparts. These findings suggest that hearing impairment may be a marker for cognitive dysfunction in adults age 65 and older.

Objectives: Analysis of outcomes of a cohort of patients with esthesioneuroblastoma. Design: Retrospective cohort analysis. Setting: Patients presenting with esthesioneuroblastoma from 1994 to 2006 in a tertiary care academic medical center. Patients: Fifteen consecutive patients diagnosed as having esthesioneuroblastoma were treated during this time period using a subcranial resection. The mean follow-up is 75 months (range, 2 to 240 mos). Results: The overall survival was 100% and the overall disease-free survival was 49% and 24% at 5 and 15 years, respectively. Patients treated with radiation therapy following surgical resection had a 5-and 15-year disease-free survival of 83.3% compared with a 5-and 15-year disease-free survival of 26.7% and 0%, respectively, for patients whose initial treatment was surgery alone. The mean time to recurrence was 82.1 months. None of the patients had a decrease in Karnofsky Performance Score following subcranial resection. Conclusions: Patients with esthesioneuroblastoma whose initial treatment consists of surgical resection followed by radiation therapy have a longer disease-free survival than patients treated with surgery alone. However, initial treatment modality did not have an effect on survival. Long-term, close follow-up is necessary to identify recurrences, which can be treated with a high degree of success.

Objectives To determine if the various imaging modalities for distant metastasis(DM) diagnosis alters life expectancy in head and neck squamous cell carcinoma(HNSCC). Study Design Retrospective Methods 170 patients (mean age 59.1; M:F 135:35) with HNSCC who developed DM were reviewed. The main outcome measures were the method of DM diagnosis and time from DM diagnosis to death while controlling for clinical parameters (age, gender, tobacco status, primary tumor site, initial TNM classification, number and site of DM, administration of palliative chemotherapy). Results Tumor subsites were: 40 oral cavity, 75 oropharynx, 36 larynx, 10 hypopharynx, 1 nasopharynx, 8 unknown primary. 16.5% (28/170) of patients had distant metastasis at presentation; the remaining 142 patients were diagnosed with DM at a median of 324 days from diagnosis. Although patients diagnosed with DM by PET scan were more likely to have multiple DM sites(p=0.0001), there were no differences in life expectancy in patients who were diagnosed with or without PET scan(median 185 vs 165 days,p=0.833). There were no differences in life expectancy based on age, gender, site of primary tumor, or number/site of DM. The use of palliative chemotherapy resulted in a significantly longer life expectancy (median 285 vs 70 days; p=0.001). Conclusions Although PET scan is more likely to diagnose multiple DM sites, there was no difference in life expectancy. Patients that are symptomatic from their distant metastasis have a worse life expectancy, and palliative chemotherapy was able to increase life expectancy, even in patients who were symptomatic from the distant metastasis.