State of the science and future directions for research on HIV and cancer : Summary of a joint workshop sponsored by IARC and NCI

An estimated 38 million people live with human immunodeficiency virus (HIV) worldwide and are at excess risk for multiple cancer types. Elevated cancer risks in people living with HIV (PLWH) are driven primarily by increased exposure to carcinogens, most notably oncogenic viruses acquired through shared transmission routes, plus acceleration of viral carcinogenesis by HIV-related immunosuppression. In the era of widespread antiretroviral therapy (ART), life expectancy of PLWH has increased, with cancer now a leading cause of co-morbidity and death. Furthermore, the types of cancers occurring among PLWH are shifting over time and vary in their relative burden in different parts of the world. In this context, the International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) convened a meeting in September 2022 of multinational and multidisciplinary experts to focus on cancer in PLWH. This report summarizes the proceedings, including a review of the state of the science of cancer descriptive epidemiology, etiology, molecular tumor characterization, primary and secondary prevention, treatment disparities and survival in PLWH around the world. A consensus of key research priorities and recommendations in these domains is also presented

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

The Science Case for Multi-Object Spectroscopy on the European ELT

This White Paper presents the scientific motivations for a multi-object spectrograph (MOS) on the European Extremely Large Telescope (E-ELT). The MOS case draws on all fields of contemporary astronomy, from extra-solar planets, to the study of the halo of the Milky Way and its satellites, and from resolved stellar populations in nearby galaxies out to observations of the earliest 'first-light' structures in the partially-reionised Universe. The material presented here results from thorough discussions within the community over the past four years, building on the past competitive studies to agree a common strategy toward realising a MOS capability on the E-ELT. The cases have been distilled to a set of common requirements which will be used to define the MOSAIC instrument, entailing two observational modes ('high multiplex' and 'high definition'). When combined with the unprecedented sensitivity of the E-ELT, MOSAIC will be the world's leading MOS facility. In analysing the requirements we also identify a high-multiplex MOS for the longer-term plans for the E-ELT, with an even greater multiplex (>1000 targets) to enable studies of large-scale structures in the high-redshift Universe. Following the green light for the construction of the E-ELT the MOS community, structured through the MOSAIC consortium, is eager to realise a MOS on the E-ELT as soon as possible. We argue that several of the most compelling cases for ELT science, in highly competitive areas of modern astronomy, demand such a capability. For example, MOS observations in the early stages of E-ELT operations will be essential for follow-up of sources identified by the James Webb Space Telescope (JWST). In particular, multi-object adaptive optics and accurate sky subtraction with fibres have both recently been demonstrated on sky, making fast-track development of MOSAIC feasible.Comment: Significantly expanded and updated version of previous ELT-MOS White Paper, so there is some textual overlap with arXiv:1303.002

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Epidemiology of human papillomavirus infections and cancers of the upper aerodigestive tract : challenges and perspectives for prevention

Au moins un cancer sur six dans le monde est causé par des agents infectieux, parmi lesquels les papillomavirus humains (HPV) qui sont responsables d'environ 600000 cas de cancer chaque année. Les HPV sont reconnus comme la cause nécessaire des cancers du col utérin, et la cause d'une fraction des cancers de l'anus, de la vulve, du vagin, du pénis, mais aussi de l'oropharynx et de la cavité buccale. Les données épidémiologiques récentes montrent une augmentation préoccupante de l'incidence des cancers HPV-induits de l'oropharynx dans certains pays développés, notamment en Amérique du Nord et en Europe du Nord. Dans le cancer du col de l'utérus, la connaissance approfondie de l'histoire naturelle de l'infection à HPV et des lésions associées a permis la mise en place du dépistage par frottis cervico-utérin, qui a donné lieu à une diminution considérable de l'incidence des cancers du col utérin. En revanche dans les cancers des voies aérodigestives supérieures (VADS) induits par l'HPV, très peu de données sur l'histoire naturelle de la maladie sont disponibles. Au- jourd'hui, le mode de transmission de l'infection à HPV et les étapes de la cancérisation des tissus des VADS restent toujours très mal compris. Si la vaccination contre l'HPV devrait avoir un impact sur l'incidence des cancers HPV-induits autres que ceux du col utérin, la couverture vaccinale reste insuffisante dans de nombreux pays pour générer une immunité de groupe, et à ce jour, aucune autre méthode de prévention des cancers des VADS HPV- induits n'est disponible. Les objectifs principaux de ce travail sont : (i) mieux définir le potentiel cancérogène des dif- férents HPV [Articles I, II et III] ; (ii) améliorer les connaissances du rôle de l'HPV dans les cancers des VADS [Articles IV et V] ; et (iii) comprendre l'histoire naturelle de l'infection à HPV et des lésions associées dans l'oropharynx [Projets I et II]At least one out of six cancers worldwide is caused by infectious agents, of which human papillomaviruses (HPV) are responsible for around 600 000 cancer cases each year. HPV are recognized as a necessary cause of cervical cancer, and the cause of a fraction of cancers of the anus, vulva, vagina, penis, but also the oropharynx. Recent epidemiological data report an alarming increase in the incidence of HPV-induced oropharyngeal cancers in some devel- oped countries, as in North America and North Europe. In cervical cancer, extended knowledge of the natural history of HPV infection and associat- ed lesions has led to the implementation of cervical pap smear screening resulting in a sub- stantial decrease in cervical cancer incidence. Conversely, in HPV-induced head and neck cancers, very few data on the natural history of the disease are available. Today, the mode of transmission of HPV infection and the steps in cancerisation of head and neck tissues are still poorly understood. Although vaccination against HPV should impact the incidence of HPV- induced cancers other than in the cervix, vaccine coverage is insufficient in many countries to generate herd immunity, and to date no other method for prevention of HPV-induced head and neck cancers is available. The main objectives of this work are: (i) to better define the oncogenic potential of the differ- ent HPV types [Articles I, II and III]; (ii) to improve the knowledge of the role of HPV in can- cers of the head and neck [Articles IV and V]; and (iii) to understand the natural history of HPV infection and associated lesions in the oropharynx [Projects I and II

Human papillomavirus genome variants and head and neck cancers: a perspective

Abstract Human papillomaviruses (HPV) cause infections that are responsible for diverse clinical manifestations from benign conditions to invasive cancer. As different HPV types are associated with variable pathogenic potential, minor genetic variations within a given high-risk HPV type might also be associated with distinct oncogenic capacities, through variable ability of persistence or risk of progression to precancer/cancer. Most recent HPV variant studies in the cervix using latest sequencing technology confirmed that minor changes in the HPV genome can have a major influence on carcinogenesis and have revealed key data that help better understand the carcinogenicity of HPV at a molecular level. Here we review the limited number of studies on HPV genome variants in head and neck cancers (HNC) and discuss their implications for cancer research in the light of accumulated knowledge for the cervix. Challenges in transposing HPV variant studies from the lower anogenital to the upper aerodigestive tract are also discussed, highlighting the main gaps of knowledge in the field of HPV-induced HNC. Specifically in the head and neck region, the lack of characterisation of precancerous lesions and the difficulty in sampling normal tissue will challenge the development of accurate studies. Although there is so far no indication that HPV variant research in HNC could directly translate into clinical application, such research is expected to be useful to disentangle unanswered questions in the pathogenesis of HNC. Yet, history of HPV variant research suggests that, to be successful, studies will require large international collaborative efforts

Etude de la fiabilité des mesures d'expression génique par RT-qPCR

LYON1-BU Santé (693882101) / SudocSudocFranceF

Human papillomavirus type 16 E6 variants in France and risk of viral persistence.

International audienceABSTRACT: BACKGROUND: Only a small portion of HPV 16 infections persist and can lead to cervical intraepithelial lesions and cancer. Factors that favour HPV persistence versus clearance are still poorly understood, but several studies have suggested that HPV intra-type variants may influence persistence and clinical outcome. The aim of this study was to assess the possible association between HPV 16 variants and the risk for viral persistence in the general population of France. METHODS: One hundred and forty two women infected with HPV 16 with normal cytology, without previous treatment for cervical lesions, and with a valid second follow-up visit 4 to 16 months later, were selected from patients participating in routine cervical cancer screening in the Reims HPV Primary Screening Cohort Study. HPV intra-type variants were determined by sequencing the HPV 16 E6 open reading frame, and were compared for viral persistence at the second visit using odds ratios (OR) to estimate relative risk. RESULTS: Although no statistically significant differences in risk for persistence were observed by the HPV 16 variant lineage, European variants containing the polymorphism 350 T (EUR-350 T) appeared to persist more often than those containing 350 G (EUR-350 G) (OR = 1.6, 95% CI = 0.8-3.4). CONCLUSIONS: No strong differences were observed in the risk of viral persistence for the HPV 16 variants that predominate in France

Prevalence and risk factors of human polyomavirus infections in non-malignant tonsils and gargles: the SPLIT study

International audienc

Diffusion Tensor Imaging to Predict Long-term Outcome after Cardiac Arrest: A Bicentric Pilot Study.

BACKGROUND: Prognostication in comatose survivors of cardiac arrest is a major clinical challenge. The authors' objective was to determine whether an assessment with diffusion tensor imaging, a brain magnetic resonance imaging sequence, increases the accuracy of 1 yr functional outcome prediction in cardiac arrest survivors. METHODS:: Prospective, observational study in two intensive care units. Fifty-seven comatose survivors of cardiac arrest underwent brain magnetic resonance imaging. Fractional anisotropy (FA), a diffusion tensor imaging value, was measured in predefined white matter regions, and apparent diffusion coefficient was assessed in predefined grey matter regions. Prediction of unfavorable outcome at 1 yr was compared using four prognostic models: FA global, FA selected, apparent diffusion coefficient, and clinical classifiers. RESULTS:: Of the 57 patients included in the study, 49 had an unfavorable outcome at 12 months. Areas under the receiver operating characteristic curve (95% CI) to predict unfavorable outcome for the FA global, FA selected, clinical, and apparent diffusion coefficient models were 0.92 (0.82-0.98), 0.96 (0.87-0.99), 0.78 (0.65-0.88), and 0.86 (0.74-0.94), respectively. The FA selected model had the best overall accuracy for predicting outcome, with a score above 0.44 having 94% (95% CI, 83-99%) sensitivity and 100% (95% CI, 63-100%) specificity for the prediction of unfavorable outcome. CONCLUSION:: Quantitative diffusion tensor imaging indicates that white matter damage is widespread after cardiac arrest. A prognostic model based on FA values in selected white matter tracts seems to predict accurately 1 yr functional outcome. These preliminary results need to be confirmed in a larger population