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Tumor infiltrating lymphocytes (TILs) aid in informing treatment for head and neck squamous cell carcinoma (HNSCC). Nevertheless, little is known about the role of diet on TILs. Immunohistologic expression of CD4, CD8, CD68, CD103, CD104 and FOXP3 were assessed in tissue microarrays from 233 previously untreated HNSCC patients. Associations between these markers and pretreatment dietary patterns were evaluated using linear regression. Associations between baseline serum carotenoids, tocopherols and TILs were assessed using logistic regression. Cox models evaluated the association between diet and TILs on overall and recurrence-free survival. Consumption of a Western dietary pattern was associated with lower CD8+ and FOXP3+ infiltrates (p-value:0.03 and 0.02, respectively). Multivariable logistic regression models demonstrated significantly higher CD8+ (OR:2.21;p-value:0.001) and FOXP3+ (OR:4.26;p-value:<0.0001) among patients with high gamma tocopherol. Conversely, high levels of xanthophylls (OR:0.12;p-value:<0.0001), lycopene (OR:0.36;p-value:0.0001) and total carotenoids(OR:0.31;p-value: <0.0001) were associated with significantly lower CD68+. Among those with high CD4+ (HR:1.77;p-value:0.03), CD68+ (HR:2.42;p-value:0.004), CD103+ (HR:3.64;p-value:0.03) and FOXP3+ (HR:3.09;p-value:0.05), having a high Western dietary pattern increased the risk of overall mortality when compared to a low Western dietary pattern. Dietary patterns and serum carotenoids may play an important role in modifying TILs, and ultimately, outcome after diagnosis with HNSCC. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is a morbid cancer with poor outcomes. Statins possess anticancer properties such as immunomodulatory and antiinflammatory effects. The objective of our study is to identify the association between statin use among untreated HNSCC patients and overall death, diseasespecific death and recurrence. HNSCC patients were recruited to participate in the University of Michigan Head and Neck Cancer Specialized Program of Research Excellence (SPORE) from 2003 to 2014. Statin use data were collected through medical record review. Participants were considered a statin user if they used a statin at or after diagnosis. Outcome data were collected through medical record review, Social Security Death Index or LexisNexis. Our analytic cohort included 1638 participants. Cox proportional hazard models were used to estimate the association between ever statin use and HNSCC outcomes. Statin use was seen in 36.0% of participants. We observed a statistically significant inverse association between ever using a statin and overall death (HR = 0.75, 95% CI = 0.63-0.88) and HNSCC-specific death (HR = 0.79, 95% CI = 0.63-0.99) and a nonstatistically significant inverse association for recurrence (HR = 0.85, 95% CI = 0.70-1.04). When investigating the association between statin use and HNSCC outcomes utilizing interaction terms between statin use and human papillomavirus (HPV), statistically significant interactions for HNSCC-specific death and recurrence were identified (HNSCC-specific death: HPV-positive HR = 0.41, 95% CI = 0.21-0.84; HPV-negative HR = 1.04, 95% CI = 0.71-1.51; p-int=0.02; recurrence: HPV-positive HR = 0.49, 95% CI = 0.29-0.84; HPV-negative HR = 1.03, 95% CI = 0.74-1.43; p=int-0.02). Statin use may be protective for adverse outcomes in HNSCC patients, particularly those with HPV-positive disease. If true, these findings could have a meaningful impact on tertiary prevention for this cancer [ABSTRACT FROM AUTHOR]

Background: There are limited treatment options for unresectable recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Vascular endothelial growth factor is of significant interest for targeted therapy in R/M HNSCC because of its central role in tumorigenesis and immunosuppression. Axitinib is a potent inhibitor of vascular endothelial growth factor receptor (VEGFR) 1 , VEGFR2, VEGFR3, platelet‐derived growth factor receptor, as well as c‐kit and offers such an approach. Methods: This article reports the results of a phase 2 trial evaluating axitinib in R/M HNSCC according to the Choi criteria for radiographic response assessment. The primary endpoint of this trial was 6‐month overall survival. RESULTS: Twenty‐nine patients were enrolled, and 28 were evaluable for a response. Patients were heavily pretreated with 61% having had at least 1 previous systemic treatment in the metastatic setting (range, 0‐5). The median overall survival of 9.8 months and the 6‐month overall survival rate of 70% met the protocol‐defined criteria for clinical efficacy. The best overall response rate was 42%. Correlative analyses demonstrated that PI3K signaling pathway alterations were associated with an increased response to therapy (75% vs 17%). A marked response to therapy was seen in a subgroup of patients who were treated with an immune checkpoint inhibitor after progression on axitinib. Conclusions: Treatment with axitinib is associated with improved survival in patients with heavily pretreated head and neck cancer, and PI3K pathway alterations may serve as a biomarker for response. Further investigation is warranted to evaluate axitinib in biomarker‐selected populations, especially in combination with immune checkpoint inhibitor therapy. Lay Summary: Metastatic head and neck squamous cancer is an incurable disease with limited treatment options and a poor prognosis.This study is the first to demonstrate that the targeted oral drug axitinib improves survival in patients with heavily pretreated metastatic head and neck cancer.Furthermore, patients whose tumors have specific mutations derive the greatest benefit from therapy.The investigation of axitinib alone or in combination with immunotherapy in a genomic biomarker–selected population is warranted. This study demonstrates that treatment with axitinib improves survival in patients with heavily pretreated recurrent or metastatic head and neck squamous cell carcinoma, that alternative response criteria enable the identification of patients with atypical radiographic responses, and that patients with PI3K pathway alterations may derive exceptional benefit from therapy. Clinically, this study provides evidence for the evaluation of axitinib alone or in combination with immunotherapy in a genomic biomarker–selected population. [ABSTRACT FROM AUTHOR]

Type-I interferon (IFN-I) signaling is critical to maintaining antigen-presenting cell function for anti-tumor immunity. However, recent studies have suggested that IFN-I signaling may also contribute to more aggressive phenotypes, raising the possibility that IFN-I downstream signaling in cancer and myeloid cells may exert dichotomous functions. We analyzed the clinicopathologic correlation of cancer-specific IFN-I activation in 195 head and neck squamous cell carcinoma patients. We also characterized the immune impact of IFN-I receptor (IFNAR1)-deficiency in syngeneic tumor models using biochemistry, flow cytometry, and single-cell RNA-Seq. We stained HNSCC tissue microarrays with a sensitive IFN-I downstream signaling activation marker, MX1, and quantitated cancer cell-specific MX1 staining. Kaplan-Meier analysis revealed that MX1-high tumors exhibited worse survival, a phenotype that depends on the number of CD8+ intratumoral T-cells. We found that cancer-specific IFNAR1 engagement promotes cancer stemness and higher expression levels of suppressive immune checkpoint receptor ligands in cancer-derived exosomes. Notably, mice bearing Ifnarl-deficient tumors exhibited lower tumor burden, increased T-cell infiltration, reduced exhausted CD4+PD1high T-cells, and increased effector population CD8+IFN-γ+ T-cells. Then, we performed single-cell RNA-sequencing and discovered that cancer-specific IFN-I signaling not only restricts effector cells expansion but also dampens their functional fitness. The beneficial role of IFN-I activation is largely dependent on the myeloid compartment. Cancer-specific IFN-I receptor engagement promotes cancer stemness and the release of cancer-derived exosomes with high expression levels of immune checkpoint receptor ligands. Cancer-specific IFN-I activation is associated with poor immunogenicity and worse clinical outcomes in HNSCC. [ABSTRACT FROM AUTHOR]

Background  Sinonasal melanoma is a rare disease with a high mortality rate. The surgical management paradigm has significantly changed over the past decade with the introduction of expanded endonasal techniques. There have also been advances in management of metastatic and locally advanced disease with the advent of immunotherapy. Methods  Single-institution retrospective review of adult patients with sinonasal melanoma, surgically managed at the University of Michigan over a 9-year period. Thirty-one patients met inclusion criteria. All patients were retrospectively staged according to the 7th Edition AJCC staging system for mucosal melanoma. Parameters that may affect survival were analyzed using Cox's proportional hazard models and survival outcomes were analyzed with the Kaplan–Meier method. Additionally, a review of three patients with distant metastatic disease receiving immunotherapy is presented. Results  Most patients were managed endoscopically (67%), and had stage III disease (71%). However, 57% of stage IVB tumors were successfully managed endoscopically. Stage statistically impacted overall survival whereas distant control was impacted by stage, site of origin, mitotic rate, and necrosis. The 2-year overall survival for all stages was 77% which declined with advanced disease. Two-year locoregional control and distant control showed similar trends. Conclusion  Treatment of sinonasal melanoma has drastically changed over the past decade with increased use of expanded endonasal techniques. Our review revealed excellent 2-year overall survival in stage III disease with an appreciable decline in survival in more advanced disease. Immunotherapy may play a large role is future management given the high-risk of distant metastasis. [ABSTRACT FROM AUTHOR]

Objective: Peritonsillar abscess (PTA) is a common infectious complication of pharyngeal infection managed by otolaryngologists and emergency room physicians. Streptococcus and Fusobacterium (e.g., Fusobacterium necrophorum, FN) species are commonly isolated pathogens. The aim of this study was to determine the implication of culture results on abscess recurrence following drainage.Methods: Single-institution retrospective review of patients treated at the University of Michigan between 2000 and 2017. Demographic and clinical outcome data were analyzed, including treatment details, culture data, and recurrence.Results: One hundred fifty-six of the 990 patients in our study developed recurrence of their abscess (16%). The age ranges most susceptible to recurrence included adolescent (22.9%) and young adult groups (17.1%). Recurrent patients were more likely to have experienced acute progression of symptoms (79% vs. 71%, P = 0.03), trismus (67% vs. 55%, P = 0.006), voice changes (65% vs. 57%, P = 0.04), and dysphagia (72% vs. 61%, P = 0.01) compared to nonrecurrent patients. They were also more likely to have clinical lymphadenopathy noted on initial examination (67% vs. 56%, P = 0.009). Culture data was sent for 852 patients (86%). The presence of FN was significantly more prevalent in the recurrent group (P < 0.0001).Conclusion: There is a high observed prevalence of FN species within PTA aspirates in the recurrent PTA population. PTA aspirate should be sent for anaerobic growth to screen for Fusobacterium species. In addition, follow-up and lower threshold for subsequent tonsillectomy should be considered in this at-risk group.Level Of Evidence: 3 Laryngoscope, 129:1567-1571, 2019. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: An uncommon phenomenon in relation to the peritonsillar abscess (PTA) is the intratonsillar abscess (ITA) or formation of an abscess within tonsillar parenchyma. This study sought to characterize our experience with diagnosis and management of ITAs in the context of the PTA patient population.Study Design: Case-control series.Methods: This is a single-institution retrospective review of patients treated at the University of Michigan between 2000 and 2017.Results: Six hundred fifty-five adult patients were identified. The incidence of ITA within the PTA population was 7% (n = 43). Patients with ITA had lower mean white blood cell count (P = .03), lower proportion of trismus (P < .0001), otalgia (P = .007), vocal changes (P < .0001), and fewer incidences of acute progression of symptoms (P = .0007). On multivariable analysis, ITA patients were noted to be older, present with a longer duration of symptoms, and have greater incidence of neck pain and lymphadenopathy. Drainage was attempted in fewer ITA patients and was rarely successful (15%) in comparison to successful drainage for PTA patients (69%) (P < .0001).Conclusions: Symptomatology differs for ITA, as fewer present with the classic PTA symptoms of otalgia, trismus, and voice alterations. The lack of classic symptoms likely leads to delayed presentation. A greater number of ITA patients presented with neck pain and lymphadenopathy. In the ITA population, aspiration attempts were more infrequent and less successful in yielding purulence. Given infrequent yield of pus and low overall recurrence rate, the diagnosing clinician should consider medical management in this distinct patient population.Level Of Evidence: 4 Laryngoscope, 129:1354-1359, 2019. [ABSTRACT FROM AUTHOR]

Background: Recurrent laryngeal squamous cell carcinomas (LSCCs) are associated with poor outcomes, without reliable biomarkers to identify patients who may benefit from adjuvant therapies. Given the emergence of tumor-infiltrating lymphocytes (TIL) as a biomarker in head and neck squamous cell carcinoma, we generated predictive models to understand the utility of CD4+, CD8+ and/or CD103+ TIL status in patients with advanced LSCC.Methods: Tissue microarrays were constructed from salvage laryngectomy specimens of 183 patients with recurrent/persistent LSCC and independently stained for CD4+, CD8+, and CD103+ TIL content. Cox proportional hazards regression analysis was employed to assess combinations of CD4+, CD8+, and CD103+ TIL levels for prediction of overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in patients with recurrent/persistent LSCC.Results: High tumor CD103+ TIL content was associated with significantly improved OS, DSS, and DFS and was a stronger predictor of survival in recurrent/persistent LSCC than either high CD8+ or CD4+ TIL content. On multivariate analysis, an "immune-rich" phenotype, in which tumors were enriched for both CD103+ and CD4+ TILs, conferred a survival benefit (OS hazard ratio: 0.28, p = 0.0014; DSS hazard ratio: 0.09, p = 0.0015; DFS hazard ratio: 0.18, p = 0.0018) in recurrent/persistent LSCC.Conclusions: An immune profile driven by CD103+ TIL content, alone and in combination with CD4+ TIL content, is a prognostic biomarker of survival in patients with recurrent/persistent LSCC. Predictive models described herein may thus prove valuable in prognostic stratification and lead to personalized treatment paradigms for this patient population. [ABSTRACT FROM AUTHOR]

Background: Accurate, individualized prognostication in patients with oropharyngeal squamous cell carcinoma (OPSCC) is vital for patient counseling and treatment decision making. With the emergence of human papillomavirus (HPV) as an important biomarker in OPSCC, calculators incorporating this variable have been developed. However, it is critical to characterize their accuracy prior to implementation.Methods: Four OPSCC calculators were identified that integrate HPV into their estimation of 5-year overall survival. Treatment outcomes for 856 patients with OPSCC who were evaluated at a single institution from 2003 through 2016 were analyzed. Predicted survival probabilities were generated for each patient using each calculator. Calculator performance was assessed and compared using Kaplan-Meier plots, receiver operating characteristic curves, concordance statistics, and calibration plots.Results: Correlation between pairs of calculators varied, with coefficients ranging from 0.63 to 0.90. Only 3 of 6 pairs of calculators yielded predictions within 10% of each other for at least 50% of patients. Kaplan-Meier curves of calculator-defined risk groups demonstrated reasonable stratification. Areas under the receiver operating characteristic curve ranged from 0.74 to 0.80, and concordance statistics ranged from 0.71 to 0.78. Each calculator demonstrated superior discriminatory ability compared with clinical staging according to the seventh and eighth editions of the American Joint Committee on Cancer staging manual. Among models, the Denmark calculator was found to be best calibrated to observed outcomes.Conclusions: Existing calculators exhibited reasonable estimation of survival in patients with OPSCC, but there was considerable variability in predictions for individual patients, which limits the clinical usefulness of these calculators. Given the increasing role of personalized treatment in patients with OPSCC, further work is needed to improve accuracy and precision, possibly through the identification and incorporation of additional biomarkers. [ABSTRACT FROM AUTHOR]