Importance of the immune system in head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) are a heterogeneous group of tumors, mainly caused by exposure to cigarette smoke and/or alcohol. In recent years, a virally driven subset of cancers driven by human papillomavirus subtype 16 [HPV-16]) has emerged. Our own data and data from other groups have demonstrated the favorable clinical outcome of HPV-driven oropharyngeal tumors and in both HPV+ and HPV- cancers the importance of a high density of tumor-associated lymphocytes for survival. These data underpin manipulation and activation of the patients' immune system by treatment, and as a result immunotherapy is rapidly taking its place in the management of HNSCC. Here we review the role the immune system in relation to HNSCC and consider the implications these have for HNSCC immunotherapy. Studies to quantify survival benefits and treatment-associated toxicities are ongoing.

Impact of social deprivation on the outcome of major head and neck cancer surgery in England: A national analysis.

BACKGROUND: Socioeconomic status plays an important role in the incidence and prognosis of many cancers. We examined the relationship between social deprivation and clinical outcomes in patients undergoing major surgery for head and neck cancer. METHODS: A retrospective population-based observational study was performed. Patients undergoing head and neck surgical procedures in England between 2002 and 2012 were identified. This totaled 5051 patients in the less socially deprived (LSD) and 7282 in the more socially deprived (MSD) group. RESULTS: MSD patients were younger (61 vs 63) and were more likely to present with hypopharyngeal-laryngeal cancers (41% vs 30%). They had higher burdens of morbidity and more frequently required emergency surgery (odds ratio [OR] 1.74 [95% CI 1.52-1.99]). Following surgery, MSD patients had higher lengths of inpatient stay (OR 1.72 [95% CI 1.57-1.88]) and higher proportions of both inpatient (OR 1.47 [95% CI 1.19-1.82]) and overall mortality (OR 1.34 [95% CI 1.24-1.45]). CONCLUSION: Increasing socioeconomic deprivation is associated with poor health outcomes in patients with head and neck cancer.

Timing of neck dissection in association with transoral surgery: A systematic review.

BACKGROUND: The purpose of this study was to present our evaluation of the importance of timing (early vs synchronous vs delayed) in conjunction with transoral laser surgery for head and neck squamous cell carcinoma (HNSCC). METHODS: Articles addressing surgical management via transoral laser surgery for HNSCC were included for review. RESULTS: Twenty-six articles fulfilled our criteria. The overall 5-year disease-specific survival (DSS) was 75.6% (95% confidence interval [CI], 67.3-83.9) and locoregional control was 87.3% (95% CI, 82.3-92.1), respectively. In the synchronous neck dissection group, the mean locoregional control was 89.9% (95% CI, 84.8-95.1) versus 84.5% (95% CI, 56.2-112.7) for the delayed neck dissection group. From studies in which complications were explicitly given, a bleeding rate of 5.3% (95% CI, 3.6-6.9) was established. There were 11.1% of patients who underwent a tracheostomy. CONCLUSION: There is no evidence to indicate that timing of neck dissection after transoral laser surgery for HNSCC has any effect on overall survival (OS). © 2016 Wiley Periodicals, Inc. Head Neck, 2016 © 2016 Wiley Periodicals, Inc. Head Neck 39: 1020-1032, 2017.

Head and Neck Squamous Cell Carcinomas Are Characterized by a Stable Immune Signature Within the Primary Tumor Over Time and Space.

Purpose: Genetic and morphologic heterogeneity is well-documented in solid cancers. Immune cells are also variably distributed within the tumor; this heterogeneity is difficult to assess in small biopsies, and may confound our understanding of the determinants of successful immunotherapy. We examined the transcriptomic variability of the immunologic signature in head and neck squamous cell carcinoma (HNSCC) within individual tumors using transcriptomic and IHC assessments.Experimental Design: Forty-four tumor biopsies from 16 HNSCC patients, taken at diagnosis and later at resection, were analyzed using RNA-sequencing. Variance filtering was used to identify the top 4,000 most variable genes. Principal component analysis, hierarchical clustering, and correlation analysis were performed. Gene expression of CD8A was correlated to IHC analysis.Results: Analysis of immunologic gene expression was highly consistent in replicates from the same cancer. Across the cohort, samples from the same patient were most similar to each other, both spatially (at diagnosis) and, notably, over time (diagnostic biopsy compared with resection); comparison of global gene expression by hierarchical clustering (P ≤ 0.0001) and correlation analysis [median intrapatient r = 0.82; median interpatient r = 0.63]. CD8A gene transcript counts were highly correlated with CD8 T-cell counts by IHC (r = 0.82).Conclusions: Our data demonstrate that in HNSCC the global tumor and adaptive immune signatures are stable between discrete parts of the same tumor and also at different timepoints. This suggests that immunologic heterogeneity may not be a key reason for failure of immunotherapy and underpins the use of transcriptomics for immunologic evaluation of novel agents in HNSCC patients. Clin Cancer Res; 23(24); 7641-9. ©2017 AACR.