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.

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. 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 was correlated to IHC analysis. 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 ( ≤ 0.0001) and correlation analysis [median intrapatient = 0.82; median interpatient = 0.63]. gene transcript counts were highly correlated with CD8 T-cell counts by IHC ( = 0.82). 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. .

Ten hospitals managing drug-resistant tuberculosis (TB) in Pakistan. To assess the implementation of TB infection control (IC) practices and reasons for non-adherence to guidelines. This was a descriptive study conducted between April and October 2016 with three components: 1) non-participant observation of service delivery areas (SDAs) ( = 82) in hospitals ( = 10) using structured checklists; 2) exit interviews with 100 patients (10 per hospital); and 3) interviews with 100 health-care workers (HCWs, 10/hospital). Of the 82 SDAs, posters were displayed in 34 (41%), mechanical ventilation was implemented in 79% and functional ultraviolet germicidal irradiation (UVGI) was available in only 26%. Patient interviews showed 50-65% adherence to triage and use of personal protective measures. Key reasons for non-adherence were lack of adequate supplies, discomfort using N-95 masks, a lack of knowledge or training, perceived non-cooperation by patients, poor maintenance of mechanical ventilators and UVGI due to unstable electricity supply, a lack of clarity in roles (no-one designated in charge) and staff shortages and subsequent workloads. Adherence to natural ventilation usage was poor for reasons related to climate and privacy. Implementation of TBIC measures in hospitals was suboptimal. Urgent measures need to be put in place, including retraining of HCWs, addressing weaknesses in mask and poster supplies and constant supervision and monitoring.