High EGFR gene copy number by FISH is frequent in HNSCC and is a poor prognostic indicator. Additional investigation is indicated to determine the biologic significance and implications for EGFR inhibitor therapies in HNSCC.

Objectives/Hypothesis: Idiopathic subglottic stenosis (iSGS) is a rare and potentially life-threatening disease marked by recurrent and progressive airway obstruction frequently requiring repeated surgery to stabilize the airway. Unknown etiology and low disease prevalence have limited the ability to characterize the natural history of iSGS and resulted in variability in surgical management. It is uncertain how this variation relates to clinical outcomes. Study Design: Medical record abstraction. Methods: Utilizing an international, multi-institutional collaborative, we collected retrospective data on patient characteristics, treatment, and clinical outcomes. We investigated variation between and within open and endoscopic treatment approaches and assessed therapeutic outcomes; specifically, disease recurrence and need for tracheostomy at last follow-up. Results: Strikingly, 479 iSGS patients across 10 participating centers were nearly exclusively female (98%, 95% confidence interval [CI], 96.1–99.6), Caucasian (95%, 95% CI, 92.2–98.8), and otherwise healthy (mean age-adjusted Charlson Comorbidity Index 1.5; 95% CI, 1.44–1.69). The patients presented at a mean age of 50 years (95% CI, 48.8–51.1). A total of 80.2% were managed endoscopically, whereas 19.8% underwent open reconstruction. Endoscopic surgery had a significantly higher rate of disease recurrence than the open approach (chi2 = 4.09, P = 0.043). Tracheostomy was avoided in 97% of patients irrespective of surgical approach (95% CI, 94.5–99.8). Interestingly, there were outliers in rates of disease recurrence between centers using similar treatment approaches. Conclusion: Idiopathic subglottic stenosis patients are surprisingly homogeneous. The heterogeneity of treatment approaches and the observed outliers in disease recurrence rates between centers raises the potential for improved clinical outcomes through a detailed understanding of the processes of care.

Human papillomavirus (HPV) is associated with a subset of head and neck squamous cell carcinoma (HNSCC). Between 15% and 35% of HNSCCs harbor HPV DNA. Demographic and exposure differences between HPV-positive (HPV + ) and negative (HPV À ) HNSCCs suggest that HPV + tumors may constitute a subclass with different biology, whereas clinical differences have also been observed. Gene expression profiles of HPV + and HPV À tumors were compared with further exploration of the biological effect of HPV in HNSCC. Thirty-six HNSCC tumors were analyzed using Affymetrix Human 133U Plus 2.0 GeneChip and for HPV by PCR and real-time PCR. Eight of 36 (22%) tumors were positive for HPV subtype 16. Statistical analysis using Significance Analysis of Microarrays based on HPV status as a supervising variable resulted in a list of 91genes that were differentially expressed with statistical significance. Results for a subset of these genes were verified by real-time PCR. Genes highly expressed in HPV + samples included cell cycle regulators (p16 INK4A , p18, and CDC7) and transcription factors (TAF7L, RFC4, RPA2, andTFDP2).The microarray data were also investigated by mapping genes by chromosomal location (DIGMAP). A large number of genes on chromosome 3q24-qter had high levels of expression in HPV + tumors. Further investigation of differentially expressed genes may reveal the unique pathways in HPV + tumors that may explain the different natural history and biological properties of these tumors. These properties may be exploited as a target of novel therapeutic agents in HNSCC treatment.Head and neck cancer remains one of the most devastating cancers in the United States. Development of the vast majority of these tumors has been attributed to use of tobacco and ethanol products, but a significant portion of these tumors are associated with human papillomavirus (HPV; refs. 1, 2). Infection with HPV is associated with malignant and premalignant lesions of the uterine, cervix, vulva, penis, conjunctiva, and upper aerodigestive tract (for review, see ref.3). Over 100 subtypes of HPV have been described in humans, with HPV type 8, 11, 16, and 18 being associated with the majority of human disease. In the cervix, a distinction is made between ''low-risk'' (types 8 and 11) and ''high-risk'' (types 16 and 18) HPV, depending on their association with premalignant and malignant lesions, respectively. Reports of the prevalence of HPV infection in head and neck squamous cell carcinoma (HNSCC) indicate that 15% to 35% of HNSCC may harbor HPV sequences, depending on the detection method used (4). DNA amplification by PCR remains the most sensitive technique to detect HPV, with almost 35% of HNSCCs yielding HPV-specific amplification products, although this result may be biased because of contamination problems associated with PCR. HPV is most commonly found in tonsillar tumors (45-100%; ref. 5) with HPV type 16 (HPV16) being found in the vast majority and HPV18 associated with most others (6).There INK4A alterations are common (50% and ...