Landscape assessment for gender neutral human papillomavirus vaccination recommendations including head and neck cancer burden data.

INTRODUCTION: Head and neck cancers (HNC) accounted for over 450,000 deaths and 900,000 cases in 2018 worldwide. Of those, 38,000 cases were attributable to human papillomavirus (HPV). HNC is two to four times more prevalent in men than in women. The incidence of oropharyngeal cancers (OPC) and oral cavity cancers caused by HPV has increased in recent decades. Given the substantial burden of HPV-related HNC in males, this study aimed to assess whether and how national agencies included HPV-related HNC when evaluating HPV genderneutral vaccination (GNV) programs. METHODS: A systematic literature review was conducted in MEDLINE® and EMBASE®, and on the websites of selected national agencies. RESULTS: Searches identified a potential 205 records; seventeen were eligible for the review. Seventy percent of assessments were published by European countries and most were recent (2014-2019). Eleven (65%) reports considered OPC when discussing HNC, and a few included other anatomic sites. All reports that considered incidence data were in consensus that incidence of OPC was higher in men and showed that the mortality rates for HPV-related HNC were also higher in men. When looking at the economic impact, the incremental cost-effectiveness ratios in the assessments varied widely, as the inputs into the analyses were heterogeneous. However, several reports concluded GNV programs were likely to be cost-effective versus not vaccinating males. CONCLUSION: The burden of HPV-related HNC in the general male population has been recognized by several Heatlth Technology Assessment (HTA) agencies and National Immunization Technical Advisory Groups (NITAGs) when evaluating HPV GNV programs. The assessments identified on GNV programs strongly indicate a cost-effective clinical benefit. Nevertheless, the epidemiological burden of HNC may have been underestimated in some countries due to limited data. Further research is crucial to obtain more robust data that will help address the information gap in epidemiological and economic burden of HPV-associated HNC in men.

A Genetic Screen Reveals an Unexpected Role for Yorkie Signaling in JAK/STAT-Dependent Hematopoietic Malignancies in Drosophila melanogaster.

A gain-of-function mutation in the tyrosine kinase JAK2 (JAK2V617F ) causes human myeloproliferative neoplasms (MPNs). These patients present with high numbers of myeloid lineage cells and have numerous complications. Since current MPN therapies are not curative, there is a need to find new regulators and targets of Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling that may represent additional clinical interventions . Drosophila melanogaster offers a low complexity model to study MPNs as JAK/STAT signaling is simplified with only one JAK [Hopscotch (Hop)] and one STAT (Stat92E). hopTumorous-lethal(Tum-l) is a gain-of-function mutation that causes dramatic expansion of myeloid cells, which then form lethal melanotic tumors. Through an F1 deficiency (Df) screen, we identified 11 suppressors and 35 enhancers of melanotic tumors in hopTum-l animals. Dfs that uncover the Hippo (Hpo) pathway genes expanded (ex) and warts (wts) strongly enhanced the hopTum-l tumor burden, as did mutations in ex, wts, and other Hpo pathway genes. Target genes of the Hpo pathway effector Yorkie (Yki) were significantly upregulated in hopTum-l blood cells, indicating that Yki signaling was increased. Ectopic hematopoietic activation of Yki in otherwise wild-type animals increased hemocyte proliferation but did not induce melanotic tumors. However, hematopoietic depletion of Yki significantly reduced the hopTum-l tumor burden, demonstrating that Yki is required for melanotic tumors in this background. These results support a model in which elevated Yki signaling increases the number of hemocytes, which become melanotic tumors as a result of elevated JAK/STAT signaling.