Mark E. Zafereo

Squamous cell carcinoma of the head and neck in never smoker–never drinkers: A descriptive epidemiologic study

While the attributed risk factors for the vast majority of patients with squamous cell carcinoma of the head and neck (SCCHN) are smoking and alcohol abuse, there appears to be a rising proportion of SCCHN patients who report no significant smoking or drinking history. This study reports the demographic and potential risk factors of a large series of never smoker–never drinker (NSND) patients.

The role of salvage surgery in patients with recurrent squamous cell carcinoma of the oropharynx

The objective of this study was to comprehensively review overall survival, functional outcomes, and prognostic factors in patients who underwent salvage surgery for locally recurrent squamous cell carcinoma of the oropharynx (SCCOP) after initial radiotherapy.

Novel MYBL1 Gene Rearrangements with Recurrent MYBL1–NFIB Fusions in Salivary Adenoid Cystic Carcinomas Lacking t(6;9) Translocations

Purpose: Adenoid cystic carcinoma (ACC) is an indolent salivary gland malignancy, characterized by t(6;9) translocations and MYB–NFIB gene fusions in approximately 50% of the tumors. The genetic alterations underlying t(6;9)-negative and t(6;9)-positive/MYB–NFIB fusion–negative ACC remain unknown. To uncover the genetic alterations in ACC lacking the canonical translocation and fusion transcript and identify new abnormalities in translocation positive tumors. Experimental Design: We performed whole-genome sequencing in 21 salivary ACCs and conducted targeted molecular analyses in a validation set (81 patients). Microarray gene-expression data were also analyzed to explore the biologic differences between fusion positive and negative tumors. Results: We identified a novel MYBL1–NFIB gene fusion as a result of t(8;9) translocation and multiple rearrangements in the MYBL1 gene in 35% of the t(6;9)-negative ACCs. All MYBL1 alterations involved deletion of the C-terminal negative regulatory domain and were associated with high MYBL1 expression. Reciprocal MYB and MYBL1 expression was consistently found in ACCs. In addition, 5′-NFIB fusions that did not involve MYB/MYBL1 genes were identified in a subset of t(6;9)-positive/fusion-negative tumors. We also delineated distinct gene-expression profiles in ACCs associated with the length of the MYB or MYBL1 fusions, suggesting a biologic importance of the C-terminal part of these fusions. Conclusions: Our study defines new molecular subclasses of ACC characterized by MYBL1 rearrangements and 5′-NFIB gene fusions. Clin Cancer Res; 22(3); 725–33. ©2015 AACR.

Matched Pair Analysis of Race or Ethnicity in Outcomes of Head and Neck Cancer Patients Receiving Similar Multidisciplinary Care

It is unknown whether population-level racial or ethnic disparities in mortality from squamous cell carcinoma of the head and neck (SCCHN) also occur in the setting of standardized multidisciplinary-team directed care. Therefore, we conducted a matched-pair study that controlled for several potentially confounding prognostic variables to assess whether a difference in survival exists for African American or Hispanic American compared with non-Hispanic white American SCCHN patients receiving similar care. Matched pairs were 81 African American case and 81 non-Hispanic white control patients and 100 Hispanic American cases and 100 matched non-Hispanic white controls selected from 1,833 patients of a prospective epidemiologic study of incident SCCHN within a single, large multidisciplinary cancer center. Matching variables included age (±10 years), sex, smoking status (never versus ever), site, tumor stage (T1-2 versus T3-4), nodal status (negative versus positive), and treatment. Cases and controls were not significantly different in proportions of comorbidity score, alcohol use, subsite distribution, overall stage, or tumor grade. Matched-pair and log-rank analyses showed no significant differences between cases and controls in recurrence-free, disease-specific, or overall survival. Site-specific analyses suggested that more aggressive oropharyngeal cancers occurred more frequently in minority than in non-Hispanic white patients. We conclude that minority and non-Hispanic white SCCHN patients receiving similar multidisciplinary-team directed care at a tertiary cancer center have similar survival results overall. These results encourage reducing health disparities in SCCHN through public-health efforts to improve access to multidisciplinary oncologic care (and to preventive measures) and through individual clinician efforts to make the best multidisciplinary cancer treatment choices available for their minority patients. The subgroup finding suggests a biologically based racial/ethnic disparity among oropharyngeal patients and that prevention and treatment strategies should be tailored to different populations of these patients.

Supraglottoplasty for laryngomalacia with obstructive sleep apnea

Objectives/Hypothesis: To determine if supraglottoplasty (SGP) is effective in reversing abnormal respiratory parameters in children with laryngomalacia and obstructive sleep apnea (OSA).

Incidence and pattern of second primary malignancies in patients with index oropharyngeal cancers versus index nonoropharyngeal head and neck cancers

A recent review of the Surveillance, Epidemiology, and End Results registry suggested that patients with index squamous cell carcinoma (SCC) of the oropharynx (SCCOP) are less likely to develop second primary malignancies (SPM) than patients with index SCC of nonoropharyngeal sites (oral cavity, larynx, hypopharynx). The objectives of this study were to determine the impact of index primary tumor site on SPM risk and to explore factors that potentially affect this risk within a large, prospectively accrued cohort of patients with index SCC of the head and neck (SCCHN).

Low risk of second primary malignancies among never smokers with human papillomavirus-associated index oropharyngeal cancers

Among patients with index oropharyngeal cancer, second primary malignancies (SPMs) may be less common in cases of human papillomavirus (HPV)‐associated tumors than HPV‐negative tumors. Further modification of these SPM risks by smoking has not been reported.

Complications and functional outcomes following complex oropharyngeal reconstruction

We sought to evaluate postoperative complications and functional outcomes in patients who underwent oropharyngeal reconstruction after oncologic resection.

Squamous cell carcinoma of the oral cavity often overexpresses p16 but is rarely driven by human papillomavirus

OBJECTIVE Human papillomavirus (HPV) is a causal and prognostic factor for oropharyngeal cancer, but its role in squamous cell carcinoma of the oral cavity (SCCOC) is unclear. We sought to clarify HPVs role in SCCOC. MATERIALS AND METHODS Patients with newly diagnosed SCCOC (N=460) were prospectively recruited, treated, and followed at one institution. p16/HPV status was determined by p16 immunohistochemistry (IHC) (N=210), PCR-based HPV 16/18 E6/7 DNA testing (N=403), and/or HPV in situ hybridization (ISH) (N=178). Kaplan-Meier curves and log-rank tests were used to compare survival by p16/HPV status. RESULTS p16 expression was detected in 30% of tumors (62/210) and HPV 16/18 E6/7 DNA in 28% (114/403), although correlation between these two assays was poor (r=-0.01). Patients with p16-positive tumors were more likely to be younger and have primary tumors of the oral tongue. Only 4% of tumors (7/171) were positive for HPV by ISH. Comparisons of patients with p16-positive and p16-negative tumors, patients with HPV-positive and HPV-negative tumors by PCR, and patients with HPV-positive and HPV-negative tumors by ISH showed no significant differences in disease-specific or disease-free survival by p16/HPV status. When we applied a more stringent definition of HPV positivity based on a combination of assay results, only 10 of 166 tumors were HPV positive, and there were no significant differences in demographic, exposure, clinical, or survival characteristics between these patients and the 156 HPV-negative patients. CONCLUSIONS Very few patients with SCCOC have HPV-driven tumors. SCCOC that overexpresses p16 may be a unique subset deserving of further study.

Surgical Salvage of Recurrent Cancer of the Head and Neck

The therapeutic options and prognosis for recurrent squamous cell carcinoma of the upper aerodigestive tract vary greatly depending on site, extent of disease, and previous treatment. Surgical salvage represents the primary curative option when recurrent disease is resectable. Common factors associated with poor salvage surgery outcomes include positive surgical margins, lack of disease-free interval following previous definitive radiation therapy, advanced initial and recurrent tumor stage, and presence of concomitant recurrent neck disease. Surgical salvage of oropharyngeal and hypopharyngeal recurrences after primary chemoradiation therapy is associated with significant patient morbidity and poor long-term survival. Patients with laryngeal recurrences generally have the best comparative survival and functional outcomes, while patients with oral cavity recurrences have a relatively intermediate prognosis. Nasopharyngeal recurrences have often been treated with reirradiation, but surgical salvage represents the best option for small recurrences confined to the nasopharynx. Most patients with recurrent upper aerodigestive tract squamous cell carcinoma after previous aggressive therapy are not curable, and clinical judgment in determining which patients are appropriate candidates for salvage surgery is paramount.