Immunometabolic Determinants of Chemoradiotherapy Response and Survival in Head and Neck Squamous Cell Carcinoma.

Tumor immune microenvironment and tumor metabolism are major determinants of chemoradiotherapy response. The interdependency and prognostic significance of specific immune and metabolic phenotypes in head and neck squamous cell carcinoma (HNSCC) were assessed and changes in reactive oxygen species were evaluated as a mechanism of treatment response in tumor spheroid/immunocyte co-cultures. Pretreatment tumor biopsies were immunohistochemically characterized in 73 HNSCC patients treated by definitive chemoradiotherapy and correlated with survival. The prognostic significance of CD8A, GLUT1, and COX5B gene expression was analyzed within The Cancer Genome Atlas database. HNSCC spheroids were co-cultured in vitro with peripheral blood mononuclear cells (PBMCs) in the presence of the glycolysis inhibitor 2-deoxyglucose and radiation treatment followed by PBMC chemotaxis determination via fluorescence microscopy. In the chemoradiotherapy-treated HNSCC cohort, mitochondrial-rich (COX5B) metabolism correlated with increased and glucose-dependent (GLUT1) metabolism with decreased intratumoral CD8/CD4 ratios. High CD8/CD4, together with mitochondrial-rich or glucose-independent metabolism, was associated with improved short-term survival. The Cancer Genome Atlas analysis confirmed that patients with a favorable immune and metabolic gene signature (high CD8A, high COX5B, low GLUT1) had improved short- and long-term survival. In vitro, 2-deoxyglucose and radiation synergistically up-regulated reactive oxygen species-dependent PBMC chemotaxis to HNSCC spheroids. These results suggest that glucose-independent tumor metabolism is associated with CD8-dominant antitumor immune infiltrate, and together, these contribute to improved chemoradiotherapy response in HNSCC.

Racial/ethnic variation in the prevalence of vaccine-related human papillomavirus genotypes.

Objective: There are currently three licensed human papillomavirus (HPV) vaccines that protect against cervical cancer. Here we compare the prevalence of bi-, quadri-, and nonavalent vaccine-related HPV genotypes in a multi-ethnic sample of non-Hispanic white, non-Hispanic black, Hispanic, and Asian women. Design: Patients in this analysis (n = 419) represent a subset of women with a previous abnormal Pap test participating in a clinical trial. HPV genotyping was conducted using the Roche Linear Array. Prevalent HPV genotypes were grouped according to their inclusion in each of the vaccines: bivalent (16, 18), quadrivalent (16, 18, 6, 11), and nonavalent (16, 18, 31, 33, 45, 52, 58, 6, 11). Results: The prevalence of HPV genotypes covered by the bi-/quadrivalent vaccines was lowest among non-Hispanic black (15%) and Hispanic women (20%), compared to non-Hispanic white (38%) and Asian women (38%). Across all racial/ethnic groups, a large proportion of infections (38%-49%) were with genotypes included in the nonavalent vaccine. However, the prevalence of HPV genotypes not covered by any vaccine was significantly higher among non-Hispanic black (36%) and Hispanic women (42%), compared to non-Hispanic white (24%) and Asian women (16%) (p < 0.001). Racial/ethnic differences in HPV genotype prevalence were observed when controlling for demographic and sexual behavior characteristics, as well as when restricting the analysis to women with CIN 2+. Conclusion: Our data suggest racial/ethnic differences in the prevalence of vaccine-related HPV genotypes. In particular, non-Hispanic black and Hispanic women had the lowest prevalence of HPV genotypes covered by the bi-/quadrivalent vaccines. While a large proportion of their infections were covered by the nonavalent vaccine, non-Hispanic black and Hispanic women also had the highest prevalence of HPV genotypes not covered by any vaccine.

Use of Audiometric Measurement for Assessment of Vocal-Fold Function in Postextubation Infants.

Importance: Infants with vocal-fold motion impairment (VFMI) have an increased risk of aspiration and pulmonary complications. Flexible nasolaryngoscopy (FNL) is the gold standard for evaluation of vocal-fold mobility. Although safe, FNL causes measurable physiologic changes. Noxious stimuli, especially in neonates in the cardiovascular intensive care unit, may cause imbalance between the pulmonary and systemic circulations and potentially circulatory collapse. Objective: To examine whether bedside measurement of infant cry volume using a smartphone application can be a screening tool for vocal-fold movement in FNL. Design, Study, and Participants: This case-control study performed from December 1, 2013, through January 31, 2015, included 42 infants in the intensive care unit at Texas Children's Hospital, Houston. Main Outcomes and Measures: Patient cry volume in decibels was recorded using a smartphone application placed 12 in from their mouth. Results: Forty-two infants were identified at the intensive care unit (median age, 33 days; 20 [48%] female and 22 [52%] male), 21 with VFMI and 21 without, based on FNL findings. A statistically significant difference was found in the mean cry volume of infants with (76.60 dB) and without (85.72 dB) VFMI. The absolute difference in the mean cry volume was 9.12 dB (95% CI, 2.74-15.50 dB). A cry volume of 90 dB or greater had a sensitivity of 90.4% (95% CI, 71%-97%) for identification of normal vocal-fold mobility. A cry volume of 75 dB or less had a specificity of 90.5% (95% CI, 71%-97%) for the identification of VFMI. The mean (SE) area under the receiver operating characteristic curve was 0.721 (0.080) (95% CI, 0.565-0.877). The cry volume, however, was not a good screen for aspiration. Conclusions and Relevance: Bedside measurement of the cry volume with a smartphone application can be used by untrained health care professionals to screen patients for further evaluation of vocal-fold mobility using FNL.

Racial disparities in incidence of human papillomavirus-associated oropharyngeal cancer in an urban population.

BACKGROUND: Recent studies suggest that rates of human papillomavirus related oropharyngeal cancer (HPVOPC) in the US are higher in Caucasians than minorities. We hypothesized that this disparity would be less marked in a racially and ethnically diverse population from New York City. METHODS: This is a retrospective chart review of 210 patients with biopsied or surgically treated OPC at the Icahn School of Medicine at Mount Sinai (ISMMS) between 1999 and 2013. Polymerase chain reaction (PCR) was used to detect the presence of HPV-DNA in paraffin-embedded tumor blocks. Incidence of HPV-positive cancers was compared between Caucasians and minorities (defined as African Americans, Asians, and Hispanics) using Fisher's exact test. RESULTS: We found a higher incidence of HPV-positive OPC in Caucasians than racial minorities within the ISMMS population (p=0.002). HPV incidence detected by PCR was 139/165 [84.2%] for Caucasians and 28/45 [62.2%] for minorities. Specifically, there was a higher rate in Caucasians compared to African Americans (p=0.017), but no significant difference between Caucasians and Hispanics (p=0.087). CONCLUSION: We documented a disparity in incidence of HPVOPC amongst racial groups, consistent with previously reported trends from study populations in less urbanized areas. Thus we conclude that the factors underlying racial/ethnic disparities in HPVOPC incidence are likely to be similar across communities with different levels of urbanization and population diversity.

Clinical characteristics and outcomes of oropharyngeal carcinoma related to high-risk non-human papillomavirus16 viral subtypes.

BACKGROUND: The majority of human papillomavirus (HPV)-related oropharyngeal carcinomas (OPCs) are associated with HPV genotype 16; however, OPC can be associated with other high-risk non-HPV16 genotypes. METHODS: This was a retrospective analysis of patients with high-risk non-HPV16 OPC treated at a single tertiary institution. Sociodemographic and clinical information was obtained by chart review. HPV genotype was determined by polymerase chain reaction (PCR). Baseline data and outcomes were compared between HPV16 and high-risk non-HPV16 groups. RESULTS: High-risk non-HPV16 genotypes accounted for 9% of HPV-related OPC. Of the 27 total high-risk non-HPV16 OPCs, HPV35 was most prevalent (48%). High-risk non-HPV16 OPC presented at a slightly higher age (p = .021) and higher clinical T classification (p = .008) compared to HPV16 OPC, but there was no significant survival difference. CONCLUSION: Clinical characteristics of high-risk non-HPV16 OPC were largely consistent with those of HPV16 OPC. Additional multi-institutional studies will be required to demonstrate conclusively that the favorable prognosis of patients with HPV16 applies to all high-risk HPV types. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1330-1337, 2016.