William W. Shockley

Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression.

The prognostication of head and neck squamous cell carcinoma (HNSCC) is largely based upon the tumor size and location and the presence of lymph node metastases. Here we show that gene expression patterns from 60 HNSCC samples assayed on cDNA microarrays allowed categorization of these tumors into four distinct subtypes. These subtypes showed statistically significant differences in recurrence-free survival and included a subtype with a possible EGFR-pathway signature, a mesenchymal-enriched subtype, a normal epithelium-like subtype, and a subtype with high levels of antioxidant enzymes. Supervised analyses to predict lymph node metastasis status were approximately 80% accurate when tumor subsite and pathological node status were considered simultaneously. This work represents an important step toward the identification of clinically significant biomarkers for HNSCC.

Molecular subtypes in head and neck cancer exhibit distinct patterns of chromosomal gain and loss of canonical cancer genes.

Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal heterogeneous disease. Beyond the role of human papilloma virus (HPV), no validated molecular characterization of the disease has been established. Using an integrated genomic analysis and validation methodology we confirm four molecular classes of HNSCC (basal, mesenchymal, atypical, and classical) consistent with signatures established for squamous carcinoma of the lung, including deregulation of the KEAP1/NFE2L2 oxidative stress pathway, differential utilization of the lineage markers SOX2 and TP63, and preference for the oncogenes PIK3CA and EGFR. For potential clinical use the signatures are complimentary to classification by HPV infection status as well as the putative high risk marker CCND1 copy number gain. A molecular etiology for the subtypes is suggested by statistically significant chromosomal gains and losses and differential cell of origin expression patterns. Model systems representative of each of the four subtypes are also presented.

Use, accuracy, and implications for patient management of [18F]-2-fluorodeoxyglucose-positron emission/computerized tomography for head and neck tumors.

Objectives/Hypothesis: Positron emission tomography (PET) has shown promise for early detection and accurate staging of cancer patients. A limited number of studies suggest PET/computed tomography (CT) may improve these variables; however, no published study has specifically evaluated clinical outcomes with PET/CT for head and neck (HN) tumors. The current study evaluates the use, accuracy, and implications for patient management of PET/CT scans in patients with HN tumors.

Oral and plunging ranulas: What is the most effective treatment?

Preferred treatment of oral/plunging ranulas remains controversial. We present our experience with ranulas at the University of North Carolina (UNC) and review the literature.

The ability of tumor volume to predict local control in surgically treated squamous cell carcinoma of the supraglottic larynx

Pretreatment CT volumetric measurement of the primary tumor has been shown to be a predictor of local control in patients with laryngeal carcinoma treated with radiation therapy (RT) alone. A direct association has been demonstrated between tumor volume of supraglottic squamous cell carcinoma (SGSCCA) and local control. However, the association between tumor volume of SGSCCA and local control has not been investigated in patients treated surgically. The purpose of this study was to determine the relationship between SGSCCA tumor volume and local control in patients treated surgically.

Orbital osteology: a study of the surgical landmarks.

This study was conducted to re‐examine the osteological anatomy of the orbit. Previous studies examined dried human skulls; this study looks at cadaveric specimens in a population that more closely resembles the population in the United States. Measurements were made of the bony orbit to define safe distances for surgical intervention and to identify distances to intraorbital fissures, canals, and foramina. Safe distances to the optic nerve were identified by subtracting 5 mm from the shortest measured specimen. The safe distances were as follows: medial quadrant, 29 mm; inferior quadrant, 39 mm; superior quadrant, 38 mm; and lateral quadrant, 36 mm. Staying close to the bony wall, not exceeding these parameters, and careful identification of anatomical structures should keep the surgeon from inadvertent damage to the intraorbital structures.

Clear cell odontogenic carcinoma: A comprehensive analysis of treatment strategies

Odontogenic neoplasms of predominately clear cells are unusual. They represent a diagnostic dilemma, and as a result, treatment strategies are diverse. Our goal is to present two new cases, summarize reported cases of clear cell odontogenic carcinoma (CCOC), assess potential risk factors for recurrence, and propose definitive surgical and therapeutic strategies.

Scar Revision Techniques: Z-Plasty, W-Plasty, and Geometric Broken Line Closure

This article addresses the use of scar revision surgery as it relates to the use of Z-plasty, W-plasty, and geometric broken line closure. Each of these techniques is discussed in detail and the author provides perspectives regarding the indications, advantages, and limitations of each procedure. The surgeon should be experienced with each of these and apply these methods as appropriate. As with any technique, careful preoperative planning along with meticulous execution will lead to optimal results.

High XRCC1 Protein Expression Is Associated with Poorer Survival in Patients with Head and Neck Squamous Cell Carcinoma

Purpose: We evaluated X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) protein in head and neck squamous cell carcinoma (HNSCC) patients in association with outcome. Experimental Design: XRCC1 protein expression was assessed by immunohistochemical (IHC) staining of pretreatment tissue samples in 138 consecutive HNSCC patients treated with surgery (n = 31), radiation (15), surgery and radiation (23), surgery and adjuvant chemoradiation (17), primary chemoradiation (51), and palliative measures (1). Results: Patients with high XRCC1 expression by IHC (n = 77) compared with patients with low XRCC1 expression (n = 60) had poorer median overall survival (OS; 41.0 months vs. OS not reached, P = 0.009) and poorer progression-free survival (28.0 months vs. 73.0 months, P = 0.031). This association was primarily due to patients who received chemoradiation (median OS of high- and low-XRCC1 expression patients, 35.5 months and not reached respectively, HR 3.48; 95% CI: 1.44–8.38; P = 0.006). In patients treated with nonchemoradiation modalities, there was no survival difference by XRCC1 expression. In multivariable analysis, high XRCC1 expression and p16INK4a-positive status were independently associated with survival in the overall study population (HR = 2.62; 95% CI: 1.52–4.52; P < 0.001 and HR = 0.21; 95% CI: 0.06–0.71; P = 0.012, respectively) and among chemoradiation patients (HR = 6.02; 95% CI: 2.36–15.37; P < 0.001 and HR = 0.26; 95% CI: 0.08–0.92, respectively; P = 0.037). Conclusions: In HNSCC, high XRCC1 protein expression is associated with poorer survival, particularly in patients receiving chemoradiation. Future validation of these findings may enable identification of HNSCC expressing patients who benefit from chemoradiation treatment. Clin Cancer Res; 17(20); 6542–52. ©2011 AACR.

Different cellular p16 INK4a localisation may signal different survival outcomes in head and neck cancer

Background:Recently, the management of head and neck squamous cell carcinoma (HNSCC) has focused considerable attention on biomarkers, which may influence outcomes. Tests for human papilloma infection, including direct assessment of the virus as well as an associated tumour suppressor gene p16, are considered reproducible. Tumours from familial melanoma syndromes have suggested that nuclear localisation of p16 might have a further role in risk stratification. We hypothesised p16 staining that considered nuclear localisation might be informative for predicting outcomes in a broader set of HNSCC tumours not limited to the oropharynx, human papilloma virus (HPV) status or by smoking status.Methods:Patients treated for HNSCC from 2002 to 2006 at UNC (University of North Carolina at Chapel Hill) hospitals that had banked tissue available were eligible for this study. Tissue microarrays (TMA) were generated in triplicate. Immunohistochemical (IHC) staining for p16 was performed and scored separately for nuclear and cytoplasmic staining. Human papilloma virus staining was also carried out using monoclonal antibody E6H4. p16 expression, HPV status and other clinical features were correlated with progression-free (PFS) and overall survival (OS).Results:A total of 135 patients had sufficient sample for this analysis. Median age at diagnosis was 57 years (range 20–82), with 68.9% males, 8.9% never smokers and 32.6% never drinkers. Three-year OS rate and PFS rate was 63.0% and 54.1%, respectively. Based on the p16 staining score, patients were divided into three groups: high nuclear, high cytoplasmic staining group (HN), low nuclear, low cytoplasmic staining group (LS) and high cytoplasmic, low nuclear staining group (HC). The HN and the LS groups had significantly better OS than the HC group with hazard ratios of 0.10 and 0.37, respectively, after controlling for other factors, including HPV status. These two groups also had significantly better PFS than the HC staining group. This finding was consistent for sites outside the oropharynx and did not require adjustment for smoking status.Conclusion:Different p16 protein localisation suggested different survival outcomes in a manner that does not require limiting the biomarker to the oropharynx and does not require assessment of smoking status.