John K. Joe

Molecular Classification Identifies a Subset of Human Papillomavirus–Associated Oropharyngeal Cancers With Favorable Prognosis

PURPOSE We sought to determine the prevalence of biologically relevant human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OSCC). Retinoblastoma (Rb) downregulation by HPV E7 results in p16 upregulation. We hypothesized that p16 overexpression in OSCC defines HPV-induced tumors with favorable prognosis. METHODS Using real-time polymerase chain reaction for HPV16, we determined HPV16 viral load in a cohort of 79 OSCCs annotated with long-term patient follow-up. A tissue microarray including these cases was also analyzed for p53, p16, and Rb utilizing in situ quantitative protein expression analysis. Seventy-seven tumors were classified into a three-class model on the basis of p16 expression and HPV-DNA presence: class I, HPV-, p16 low; class II, HPV+, p16 low; and class III, HPV+, p16 high. RESULTS Sixty-one percent of OSCCs were HPV16+; HPV status alone was of no prognostic value for local recurrence and was barely significant for survival times. Overall survival was improved in class III (79%) compared with the other two classes (20% and 18%; P = .0095). Disease-free survival for the same class was 75% versus 15% and 13% (P = .0025). The 5-year local recurrence was 14% in class III versus 45% and 74% (P = .03). Only patients in class III had significantly lower p53 and Rb expression (P = .017 and .001, respectively). Multivariable survival analysis confirmed the prognostic value of the three-class model. CONCLUSION Using this system for classification, we define the molecular profile of HPV+ OSCC with favorable prognosis, namely HPV+/p16 high (class III). This study defines a novel classification scheme that may have value for patient stratification for clinical trials testing HPV-targeted therapies.

Presence of a tracheotomy tube and aspiration status in early, postsurgical head and neck cancer patients

We sought to investigate the effects, if any, that the presence of a tracheotomy tube has on aspiration status in early, postsurgical head and neck cancer patients.

Documentation of Variations in Sinonasal Anatomy by Intraoperative Nasal Endoscopy

Objectives: Functional endoscopic sinus surgery (FESS) requires a thorough understanding of the variability in sinonasal anatomy. Previous reports have relied primarily on anatomic studies of cadaveric specimens or skulls, or on radiographic analysis. Relatively few comparative anatomic data have been accumulated with endoscopic examination of living patients.

β-Catenin Functions Mainly as an Adhesion Molecule in Patients with Squamous Cell Cancer of the Head and Neck

Background: β-catenin, depending on subcellular localization, plays a dual role in carcinogenesis: as a signaling factor (in the nucleus) and as an adhesion molecule (in cell membrane). In this study, we sought to determine the role of β-catenin in head and neck carcinogenesis. Methods: First, we studied the incidence of mutations of β-catenin in a cohort of 60 head and neck squamous cell cancers (HNSCC). We subsequently evaluated the protein expression levels of β-catenin in a cohort of oropharyngeal squamous cell cancer tissue microarray using a novel in situ method of quantitative protein analysis and correlated those with cyclin D1 levels and clinical and pathologic data. Results: The mean follow-up time for survivors was 45 months and for all patients was 35 months. We found no mutations in the cohort of 60 HNSCC. β-catenin displayed primarily membranous expression pattern. Patients with high tumor-node-metastasis stage were more likely to have high expression of β-catenin (P = 0.040). Patients with low β-catenin expression had a local recurrence rate of 79% compared with 29% for patients with high β-catenin tumors (P = 0.0021). Univariate Cox regression revealed a hazard ratio for low β-catenin tumors of 3.6 (P = 0.004). Kaplan-Meier analysis showed that patients with low β-catenin expressing tumors trended toward worse 5-year disease-free survival (P = 0.06). In multivariate analysis, only β-catenin expression status was an independent prognostic factor (P = 0.044) for local recurrence. Tumors with high β-catenin had low cyclin D1 and vice versa (P = 0.007). Conclusions: The absence of activating β-catenin mutations combined with the inverse correlation between β-catenin levels with cyclin D1 levels and outcome suggest that β-catenin mainly functions as an adhesion and not signaling molecule in HNSCC.

Effect of Tracheotomy Tube Occlusion on Upper Esophageal Sphincter and Pharyngeal Pressures in Aspirating and Nonaspirating Patients

Abstract The biomechanics of the pharyngeal swallow in patients with a tracheotomy tube were investigated with manometry. Upper esophageal sphincter (UES) and pharyngeal pressure recordings were made with and without occlusion of the tracheotomy tube. Criteria for selection were ability to tolerate tracheotomy tube occlusion for both 5 minutes prior to and during the first manometric analysis, absence of surgery to the upper aerodigestive tract other than tracheotomy, and no history of oropharyngeal cancer or stroke. Aspiration was determined objectively by fiberoptic endoscopic evaluation of swallowing (FEES) immediately prior to manometric recording. Eleven adult individuals with tracheotomy participated; 7 swallowed successfully and 4 exhibited aspiration on FEES. The results indicated no significant effect of tracheotomy tube occlusion on UES or pharyngeal pressures in either aspirating or nonaspirating patients. It was concluded that the biomechanics of the swallow as determined by UES and pharyngeal manometric pressure measurements were not changed significantly by tracheotomy tube occlusion in aspirating or nonaspirating patients. These results support previous observations that subjects either aspirated or swallowed successfully regardless of tracheotomy tube occlusion status.

Septectomy and septal dermoplasty for the treatment of severe transfusion-dependent epistaxis in patients with hereditary hemorrhagic telangiectasia and septal perforation.

Background Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by abnormal angiogenesis with resultant telangiectasia formation in mucocutaneous tissues, visceral organs, and the central nervous system. The most common manifestation of HHT is epistaxis resulting from trauma to thin-walled telangiectasias. Many patients with HHT experience worsened epistaxis due to the presence of a septal perforation. Septal perforation in HHT patients results from aggressive noncartilage sparing treatments such as monopolar cauterization. Although the mainstay of treatment for patients with severe transfusion-dependent HHT remains to be septal dermoplasty (SD), patients with a septal perforation are less likely to have a successful outcome. In this small subset of patients, septectomy (ST) combined with SD is proposed to eliminate this variable to improve skin graft uptake and therefore outcome. This study reviews the indications, procedure, and outcome of nine patients with severe transfusion-dependent HHT and septal perforation who underwent the combined procedure of SD/ST. Methods Nine HHT patients with severe transfusion-dependent epistaxis and septal perforation underwent SD/ST at our institution over a 5-year period. Quality of life, including number of daily events of epistaxis, and transfusion requirements were determined before and after surgery. Technical aspects of the procedure as well as complications were reviewed. Results The combined procedure of SD/ST resulted in a long-lasting subjective improvement in quality of life for all patients. Similarly, transfusion requirements were reduced from 22.61 to 9.57 (p < 0.05). There were no complications or increased morbidity from the procedure. Conclusion Combined SD/ST is a safe and effective treatment for HHT patients with transfusion-dependent epistaxis and septal perforation.

Efficacy of Adjunctive Cricopharyngeus Myotomy in Supraglottic Laryngectomy

This study investigates prospectively the effect of concurrent cricopharyngeus myotomy (CPM) on swallowing following horizontal supraglottic laryngectomy (SL) using fiberoptic, radiographic, and manometric evaluations and suggests possible mechanisms regarding the role of CPM following SL. Six patients undergoing horizontal SL between 1995 and 1997 were enrolled in a prospective evaluation with a followup of 0.5–2.25 years. Three patients underwent concurrent CPM and three did not. Fiberoptic, radiographic, and manometric assessments were performed postoperatively. Although mean resting pressures at the upper esophageal sphincter were reduced significantly by myotomy (12 mm Hg) compared with nonmyotomized patients (57 mm Hg), p < 0.01, no rehabilitative advantage was observed in the former group. In fact, of the myotomized patients, two required feeding gastrostomy tubes with resumption of an oral diet in one year and in two months, respectively, while the nonmyotomized patients were all capable of resuming a full oral diet within four weeks. It appears that CPM provides no rehabilitative advantage in patients undergoing SL.