Evidence supports a role for epigenetic mechanisms in the pathogenesis of late-onset Alzheimer's disease (LOAD), but little has been done on a genome-wide scale to identify potential sites involved in disease. This study investigates human postmortem

The incidence of human papillomavirus (HPV)–related oropharynx cancer has steadily increased over the past two decades and now represents a majority of oropharyngeal cancer cases. Integration of the HPV genome into the host genome is a common event during carcinogenesis that has clinically relevant effects if the viral early genes are transcribed. Understanding the impact of HPV integration on clinical outcomes of head and neck squamous cell carcinoma (HNSCC) is critical for implementing deescalated treatment approaches for HPV⁺ HNSCC patients. RNA sequencing (RNA-seq) data from HNSCC tumors (n = 84) were used to identify and characterize expressed integration events, which were overrepresented near known head and neck, lung, and urogenital cancer genes. Five genes were recurrent, including CD274 (PD-L1). A significant number of genes detected to have integration events were found to interact with Tp63, ETS, and/or FOX1A. Patients with no detected integration had better survival than integration-positive and HPV⁻ patients. Furthermore, integration-negative tumors were characterized by strongly heightened signatures for immune cells, including CD4⁺, CD3⁺, regulatory, CD8⁺ T cells, NK cells, and B cells, compared with integration-positive tumors. Finally, genes with elevated expression in integration-negative specimens were strongly enriched with immune-related gene ontology terms, while upregulated genes in integration-positive tumors were enriched for keratinization, RNA metabolism, and translation. Implications: These findings demonstrate the clinical relevancy of expressed HPV integration, which is characterized by a change in immune response and/or aberrant expression of the integration-harboring cancer-related genes, and suggest strong natural selection for tumor cells with expressed integration events in key carcinogenic genes. Mol Cancer Res; 16(1); 90–102. ©2017 AACR.

Objectives: An effective vaccine to SARS-CoV-2 cannot be successfully deployed if a significant number of people worldwide are unwilling to accept it. We investigated the relationship between trust in scientists and medical professionals and perceptions of vaccine safety and effectiveness. We also build on past studies by exploring the relationship between confidence in global health organizations and vaccine hesitancy.Methods: We conducted an online survey in seventeen countries/territories across five world regions between May -June 2020. We assessed the relationship between COVID19 vaccine hesitancy, confidence in public health organizations, and trust in key experts and leaders.Results: Our findings strongly suggest that confidence in the World Health Organization combined with trust in domestic scientists and healthcare professionals is a strong driver of vaccine acceptance across multiple countries/territories.Conclusion: We find that hesitancy is widespread, and uptake would be insufficient to achieve herd immunity. There is widespread confidence in how public health organizations have responded to the current pandemic and this is related to vaccine acceptance. Our results also highlight the important role of trust in health care providers and scientists in reducing COVID19 vaccine hesitancy.

Oncogenic human papillomaviruses (HPV) are associated with nearly all cervical cancers and are increasingly important in the etiology of oropharyngeal tumors. HPV-associated head and neck squamous ...

Purpose: There is substantial heterogeneity within human papillomavirus (HPV)-associated head and neck cancer (HNC) tumors that predispose them to different outcomes; however, the molecular heterogeneity in this subgroup is poorly characterized due to various historical reasons. Experimental Design: We performed unsupervised gene expression clustering on deeply annotated (transcriptome and genome) HPV+ HNC samples from two cohorts (84 total primary tumors), including 18 HPV− HNC samples, to discover subtypes and characterize the differences between subgroups in terms of their HPV characteristics, pathway activity, whole-genome somatic copy number alterations, and mutation frequencies. Results: We identified two distinct HPV+ subtypes (namely HPV-KRT and HPV-IMU). HPV-KRT is characterized by elevated expression of genes in keratinocyte differentiation and oxidation–reduction process, whereas HPV-IMU has strong immune response and mesenchymal differentiation. The differences in expression are likely connected to the differences in HPV characteristics and genomic changes. HPV-KRT has more genic viral integration, lower E2/E4/E5 expression levels, and higher ratio of spliced to full-length HPV oncogene E6 than HPV-IMU; the subgroups also show differences in copy number alterations and mutations, in particular the loss of chr16q in HPV-IMU and gain of chr3q and PIK3CA mutation in HPV-KRT. Conclusions: Our characterization of two subtypes of HPV+ HNC tumors provides valuable molecular level information that point to two main carcinogenic paths. Together, these results shed light on stratifications of the HPV+ HNCs and will help to guide personalized care for HPV+ HNC patients. Clin Cancer Res; 22(18); 4735–45. ©2016 AACR.

Improved understanding of the multilayer regulation of the human genome has led to a greater appreciation of environmental, nutritional, and epigenetic risk factors for human disease. Chromatin remodeling, histone tail modifications, and DNA methylation are dynamic epigenetic changes responsive to external stimuli. Careful interpretation can provide insights for actionable public health through collaboration between population and basic scientists and through integration of multiple data sources. We review key findings in environmental epigenetics both in human population studies and in animal models, and discuss the implications of these results for risk assessment and public health protection. To ultimately succeed in identifying epigenetic mechanisms leading to complex phenotypes and disease, researchers must integrate the various animal models, human clinical approaches, and human population approaches while paying attention to life-stage sensitivity, to generate effective prescriptions for human health evaluation and disease prevention.