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.

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.

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.

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Objectives: (1) Determine whether there is a difference in the incidence of human papillomavirus (HPV)–associated oropharyngeal carcinoma (OPC) between non-Hispanic Caucasians and minorities in an institutional series drawn from the highly urbanized population of New York City. Methods: Several recent studies suggest that rates of HPV-associated OPC are higher in Caucasians than in minorities. We hypothesized that this difference would be lower in the highly diverse, urban population of New York City. This is a retrospective chart review of 240 patients with surgically treated OPC at the Icahn School of Medicine at Mount Sinai (ISMMS) between 1999 to 2013. Researchers determined age, sex, race, ethnicity, and tumor site of study participants. Polymerase chain reaction (PCR) was used to detect the presence of oncogenic HPV-DNA in paraffin 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 HPV in Caucasians than racial minorities within the ISMMS population ( P = .010). HPV incidence detected by PCR was 149 out of 192 (77.6%) for Caucasians and 28 out of 48 (58.3%) for minorities. Specifically, there was a higher incidence in Caucasians compared with African Americans ( P = .024), but no significant difference between Caucasians and Hispanics ( P = .218). There were no significant differences between the 2 cohorts in sex or age. Conclusions: The incidence of HPV-positive OPC is higher in non-Hispanic Caucasians than in minorities in New York City. This observation is consistent with previously reported trends from study populations in less urbanized areas.