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:

BACKGROUND: Extracapsular spread (ECS) in cervical lymph node metastases from head and neck squamous cell carcinoma (SCC) is regarded as an adverse prognostic factor and is often used to select patients who may benefit from adjuvant therapy. The prognostic value of ECS was evaluated for patients with oropharyngeal SCC (OPC; with known p16/human papillomavirus [HPV] status) and for patients with SCC of the oral cavity (OCC). METHODS: Disease-specific survival (DSS) was assessed among SCC patients with cervical lymph node metastases (n 5 347, including 133 patients with OPC and 214 patients with OCC). All patients were treated surgically between 1983 and 2009. ECS status was determined by pathologists at the time of initial pathologic evaluation and confirmed for this study. HPV status of patients with OPC was determined via immunohistochemistry for p16 and in situ hybridization. RESULTS: Among OCC patients, ECS was a significant, independent factor influencing DSS. For OCC patients with ECS, 3-year DSS was 45% (95% confidence interval [CI], 36%-56%); for those without ECS, 3-year DSS was 71% (95% CI, 62%-81%; P 5.0018). The effect of ECS was independent of the number of positive lymph nodes as well as other clinical, pathologic, and treatment variables. Of the 133 OPC patients, 76 (57%) were p16-positive and 57 (43%) were p16-negative. ECS status did not correlate with DSS among p16-positive or p16-negative OPC patients. CONCLUSION: ECS was not associated with worse DSS in p16-positive or p16-negative OPC patients.

Background-Human papillomavirus (HPV) has been detected in keratinizing nasopharyngeal carcinomas (NPCs), however the relationship between HPV and EBV among whites with nonkeratinizing NPCs remains unclear. The HPV, p16, and EBV status was examined in current University of Michigan NPC patients.