Safety Recommendations for Evaluation and Surgery of the Head and Neck During the COVID-19 Pandemic

Importance The rapidly expanding novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has challenged the medical community to an unprecedented degree. Physicians and health care workers are at added risk of exposure and infection during the course of patient care. Because of the rapid spread of this disease through respiratory droplets, health care workers who come in close contact with the upper aerodigestive tract during diagnostic and therapeutic procedures, such as otolaryngologists–head and neck surgeons, are particularly at risk. A set of safety recommendations was created based on a review of the literature and communications with physicians with firsthand knowledge of safety procedures during the COVID-19 pandemic. Observations A high number of health care workers were infected during the first phase of the pandemic in the city of Wuhan, China. Subsequently, by adopting strict safety precautions, other regions were able to achieve high levels of safety for health care workers without jeopardizing the care of patients. The most common procedures related to the examination and treatment of upper aerodigestive tract diseases were reviewed. Each category was reviewed based on the potential risk imposed to health care workers. Specific recommendations were made based on the literature, when available, or consensus best practices. Specific safety recommendations were made for performing tracheostomy in patients with COVID-19. Conclusions and Relevance Preserving a highly skilled health care workforce is a top priority for any community and health care system. Based on the experience of health care systems in Asia and Europe, by following strict safety guidelines, the risk of exposure and infection of health care workers could be greatly reduced while providing high levels of care. The provided recommendations, which may evolve over time, could be used as broad guidance for all health care workers who are involved in the care of patients with COVID-19

Cancer stem cells: Mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma

BackgroundCancer stem cells (CSCs) represent a subpopulation of cells responsible for tumor growth. Their role in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and metastasis remains uncertain.MethodsWound healing and an orthotopic animal model were used to study cells expressing the CSC phenotype (CD44high and aldehyde dehydrogenase [ALDH]+) and assess mobility, tumorigenesis, and metastasis. A prospective collection of 40 patient‐derived primary HNSCC specimens were analyzed for CSC‐proportion compared to clinical variables.ResultsCSCs exhibited significantly faster wound closure and greater tumorigenesis and regional metastasis in vivo than non‐CSCs. In primary patient tumors, size and advanced stage were correlated with elevated proportion of CSCs, however, not with survival.ConclusionHNSCC stem cells mediate tumorigenesis and regional metastasis in vivo. In primary patient tumors, CSC‐proportion was associated with tumor size and stage, but not with metastatic spread or survival. CSC burden alone may only represent a minor variable in understanding CSCs and metastasis. © 2014 Wiley Periodicals, Inc. Head Neck 37: 317–326, 2015Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110728/1/hed23600.pd

Predictors of survival after total laryngectomy for recurrent/persistent laryngeal squamous cell carcinoma

BackgroundTotal laryngectomy remains the treatment of choice for recurrent/persistent laryngeal squamous cell carcinoma (SCC) after radiotherapy (RT) or chemoradiotherapy (CRT). However, despite attempts at aggressive surgical salvage, survival in this cohort remains suboptimal.MethodsA prospectively maintained single‐institution database was queried for patients undergoing total laryngectomy for recurrent/persistent laryngeal SCC after initial RT/CRT between 1998 and 2015(n = 244). Demographic, clinical, and survival data were abstracted. The Kaplan‐Meier survival curves and hazard ratios (HRs) were calculated.ResultsFive‐year overall survival (OS) was 49%. Five‐year disease‐free survival (DFS) was 58%. Independent predictors of OS included severe comorbidity (Adult Comorbidity Evaluation‐27 [ACE‐27] scale; HR 3.76; 95% confidence interval [CI] 1.56‐9.06), and positive recurrent clinical nodes (HR 2.91; 95% CI 1.74‐4.88).ConclusionSevere comorbidity status is the strongest predictor of OS, suggesting that increased attention to mitigating competing risks to health is critical. These data may inform a risk prediction model to allow for focused shared decision making, preoperative health optimization, and patient selection for adjuvant therapies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139972/1/hed24918.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139972/2/hed24918_am.pd

Comprehensive review of genetic factors contributing to head and neck squamous cell carcinoma development in low‐risk, nontraditional patients

BackgroundThe past 2 decades have seen an increased incidence of head and neck squamous cell carcinoma (HNSCC) in a nontraditional, low‐risk patient population (ie, ≤45 years of age, no substance use history), owing to a combination of human papillomavirus (HPV) infection and individual genetic variation.MethodsArticles positing genetic variants as contributing factors in HNSCC incidence in low‐risk, nontraditional patients were identified using a PubMed search, reviewed in detail, and concisely summarized herein.ResultsRecent data suggest that common polymorphisms in DNA repair enzymes, cell‐cycle control proteins, apoptotic pathway members, and Fanconi anemia‐associated genes likely modulate susceptibility to HNSCC development in low‐risk, nontraditional patients.ConclusionAt present, there is a lack of robust, comprehensive data on genetic drivers of oncogenesis in low‐risk patients and a clear need for further research on genetic alterations underlying the rising incidence of HNSCC in low‐risk, nontraditional patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143606/1/hed25057_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143606/2/hed25057.pd

Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138837/1/cncr30802.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138837/2/cncr30802_am.pd

Saturated Fatty Acids Dampen the Immunogenicity of Cancer by Suppressing STING

Oncogenes destabilize STING in epithelial cell-derived cancer cells, such as head and neck squamous cell carcinomas (HNSCCs), to promote immune escape. Despite the abundance of tumor-infiltrating myeloid cells, HNSCC presents notable resistance to STING stimulation. Here, we show how saturated fatty acids in the microenvironment dampen tumor response to STING stimulation. Using single-cell analysis, we found that obesity creates an IFN-I-deprived tumor microenvironment with a massive expansion of suppressive myeloid cell clusters and contraction of effector T cells. Saturated fatty acids, but not unsaturated fatty acids, potently inhibit the STING-IFN-I pathway in HNSCC cells. Myeloid cells from obese mice show dampened responses to STING stimulation and are more suppressive of T cell activation. In agreement, obese hosts exhibited increased tumor burden and lower responsiveness to STING agonist. As a mechanism, saturated fatty acids induce the expression of NLRC3, depletion of which results in a T cell inflamed tumor microenvironment and IFN-I-dependent tumor control

Mutational profiles of persistent/recurrent laryngeal squamous cell carcinoma

BackgroundWe sought to describe targeted DNA sequencing data of persistent/recurrent laryngeal squamous cell carcinoma (LSCC) and to compare gene‐specific alteration frequencies with that of primary, untreated LSCC specimens from The Cancer Genome Atlas (TCGA).MethodsThe tumors of 21 patients with persistent/recurrent LSCC were subjected to targeted DNA sequencing using the Ion AmpliSeq Comprehensive Cancer Panel. Gene‐specific alteration frequencies were compared (Chi‐Square test) to primary, untreated LSCC sequencing data from TCGA using the cBioPortal platform.ResultsPersistent/recurrent LSCC was characterized by a high rate of inactivating alterations in TP53 (38.1%) and CDKN2A (33%), amplification events of CCND1 (19.1%), and ERBB2 (14.3%), and NOTCH1 (19.1%) mutations. Comparison of primary vs persistent/recurrent LSCC revealed significant differences in alteration frequencies of eight critical genes: BAP1, CDKN2A, DCUN1D1, MSH2, MTOR, PIK3CA, TET2, and TP53.ConclusionsOur results provide preliminary support for a distinct mutational profile of persistent/recurrent LSCC that requires validation in larger cohorts.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147873/1/hed25444.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147873/2/hed25444_am.pd

Impact of American Joint Committee on Cancer Eighth Edition clinical stage and smoking history on oncologic outcomes in human papillomavirus‐associated oropharyngeal squamous cell carcinoma

BackgroundThe purpose of this study was to evaluate the AJCC eighth edition clinical staging system for human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma and to further understand how clinical stage and smoking history affect oncologic outcomes. The purpose of this study was to present the understanding of how clinical stage and smoking history affect oncologic outcomes in human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma (SCC) is critical for selecting patients for treatment deintensification.MethodsKaplan‐Meier and Cox regression were used to evaluate overall survival (OS), locoregional recurrence‐free survival (LRFS), and distant recurrence‐free survival (DRFS). Concordance statistics (C‐indices) were used to compare discriminating ability.ResultsThe OS and DRFS but not LRFS were significantly distributed using the American Joint Committee on Cancer (AJCC) seventh and eighth editions criteria. The C‐indices for OS, LRFS, and DRFS were 0.57, 0.54, and 0.60, respectively, using the AJCC seventh edition, and 0.63, 0.53, and 0.65, respectively, using the AJCC eighth edition. On multivariate analysis, 1 + pack‐year smoking history correlated with OS (hazard ratio [HR] 1.96; 95% confidence interval [CI] 1.2‐3.1; P < .01) but not LRFS or DRFS.ConclusionThese results support implementation of the AJCC eighth edition for HPV‐associated oropharyngeal SCC. Clinical stage may be more important than smoking history in selection for deintensification.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148352/1/hed25336_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148352/2/hed25336.pd

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead