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Background: There is a need to better understand HPV vaccination (HPVv) implementation in WHO Europe Region (WHO/ER), including recommendations, funding, and vaccination coverage rates (VCR). Methods: A targeted literature review (up to 31 January 2020) was conducted using national health ministry websites, WHO database, and published studies from WHO/ER countries (n = 53). HPVv recommendations and funding data (target age, gender, schedule, setting, target and monitored VCR) for primary and catch-up cohorts were collected. Results: National recommendations for HPVv exist in 46/53 (87%) countries, of which 38 (83%), 2 (4%), and 6 (13%) countries provided full, partial, or no funding, respectively, for the primary cohort. Fully or partially funded HPVv was provided for girls only in 25/53 (47%) countries and for both boys and girls in 15/53 (28%) countries. HPVv catch-up was fully or partially funded in 14/53 (26%) countries. Among 40 countries with a national immunization program (NIP), monitored VCRs ranged from 4.3% to 99% (n = 30). Of the 10 countries reporting VCR targets, only Portugal exceeded its target. Conclusion: Of the 53 WHO/ER countries, 40 have funded HPVv NIPs, among which 30 report VCRs. Additional efforts are required to ensure HPVv NIPs are fully funded and high VCRs maintained.

Introduction: Disease prevention and improving vaccination coverage in Europe are key elements contributing to resilient health systems and ensuring better health outcomes for all. The aim of this study was to describe the immunization funding landscape across all European Union 28 countries (EU28). Areas covered: Data collected in a targeted literature review supported descriptive analysis on the different indicators that were looked at: vaccines included in the EU28 national immunization programs (NIP), national immunization funding, immunization funding per capita (2015- 2019) and percentage of health-care budget allocated to immunization. Expert opinion: Immunization funding represents a small proportion of total healthcare spend in Europe (median 0.3%). In the context of the current COVID-19 pandemic, demographic changes, and the potential introduction of new vaccines ; the need for adequate financing of immunization programs will be important, to establish resilient immunization systems and provide sustainable protection of the population against vaccine- preventable diseases.

Objectives: Vaccination is one of the most cost-effective health interventions, saving millions of people from illness, disability and death each year The COVID-19 pandemic has highlighted a need to strengthen crisis management and health systems Disease prevention and improving vaccination coverage in Europe are key elements contributing to resilient health systems and ensuring better health outcomes for all For resiliency of health systems to be enhanced, sufficient monetary resources and stability of funding must be secured The objective of the study was to understand the current immunization funding landscape across the 28 European Union countries (EU28) Methods: Targeted literature search was conducted on national government websites in EU28 to collect data on immunization budget (IB) or expenditures (IE) and healthcare budget over the period (2015-2019) WHO and OECD were used when data was not available from national sources Descriptive analyses were performed;IB or IE was calculated per capita, and as a percentage of healthcare budget Data were converted to euros (€) Results: Either, IB or IE data were available for 26 of 28 countries among which national source data were accessible for 21 countries and for the remaining five countries data were obtained from secondary sources No data were available for Belgium and Greece Over 2015 to 2019, IB or IE per capita ranged from 0 91€ (Poland) to 23€ (Sweden) IB or IE represented between 0 06% (France) and 3 44% (Luxemburg) of the healthcare budget Luxemburg and Latvia were the only countries spending more than 1% of the healthcare budget on immunization while remaining 24 countries were spending less than 0 5% Conclusions: There is a need for uniformity and availability of data, including a common definition of IB or IE throughout EU28 countries

Background: The nonavalent HPV (9vHPV) vaccine is indicated for active immunisation of individuals from the age of 9 years against cervical, vulvar, vaginal and anal premalignant lesions and cancers causally related to vaccine HPV high risk types 16, 18, 31, 33, 45, 52 and 58, and to the HPV low risk types 6 and 11, causing genital warts. Objective: To estimate the lifetime risk (up to the age of 75 years) for developing cervical cancer after vaccinating a HPV naive girl (e.g. 9 to 12 years old) with the 9vHPV vaccine in the hypothetical absence of cervical cancer screening. Methods: We built Monte Carlo simulation models using historical pre-screening age-specific cancer incidence data and current mortality data from Denmark, Finland, Norway, Sweden and the UK. Estimates of genotype contribution fractions and vaccine efficacy were used to estimate the residual lifetime risk after vaccination assuming lifelong protection. Results: We estimated that, in the hypothetical absence of cervical screening and assuming lifelong protection, 9vHPV vaccination reduced the lifetime cervical cancer and mortality risks 7-fold with a residual lifetime cancer risks ranging from 1/572 (UK) to 1/238 (Denmark) and mortality risks ranging from 1/1488 (UK) to 1/851 (Denmark). After decades of repetitive cervical screenings, the lifetime cervical cancer and mortality risks was reduced between 2- and 4-fold depending on the country. Conclusion: Our simulations demonstrate how evidence can be generated to support decision-making by individual healthcare seekers regarding cervical cancer prevention.

This systematic review assessed the global impact and effectiveness of quadrivalent human papillomavirus (HPV) vaccination on HPV infection and disease in real-world settings over a decade of use. Substantial reductions in HPV 6/11/16/18 infection, anogenital warts, and cervical lesions have been achieved., Prophylactic human papillomavirus (HPV) vaccination programs constitute major public health initiatives worldwide. We assessed the global effect of quadrivalent HPV (4vHPV) vaccination on HPV infection and disease. PubMed and Embase were systematically searched for peer-reviewed articles from January 2007 through February 2016 to identify observational studies reporting the impact or effectiveness of 4vHPV vaccination on infection, anogenital warts, and cervical cancer or precancerous lesions. Over the last decade, the impact of HPV vaccination in real-world settings has become increasingly evident, especially among girls vaccinated before HPV exposure in countries with high vaccine uptake. Maximal reductions of approximately 90% for HPV 6/11/16/18 infection, approximately 90% for genital warts, approximately 45% for low-grade cytological cervical abnormalities, and approximately 85% for high-grade histologically proven cervical abnormalities have been reported. The full public health potential of HPV vaccination is not yet realized. HPV-related disease remains a significant source of morbidity and mortality in developing and developed nations, underscoring the need for HPV vaccination programs with high population coverage.

Background: A quadrivalent human papillomavirus (HPV4) type 6/11/16/18 vaccine (GARDASIL/SILGARD®) has been licensed in many countries around the world for the prevention of cervical, vulvar, vaginal, and anal cancers and precancers, as well as external genital warts causally related to HPV types 6/11/16/18. Across 7 phase 3 clinical trials involving more than 29,000 males and females ages 9-45 years, vaccination was generally well tolerated. Because of its expected public health benefit in reducing cervical cancer and other HPV-related diseases, the vaccine has been implemented in the national vaccination programs of several countries, with over 178 million doses distributed worldwide. Methods: Extensive efforts to assess the safety of the vaccine in routine practice have been conducted over the past 9 years since licensure, including more than 15 studies in more than 1 million preadolescents, adolescents and adults from various countries. Most have been performed in the general population although there have been some in special populations (pregnant women, HIV-infected individuals and those with systemic lupus erythematosus). Results: We present a summary of the published, postlicensure safety data from active and passive surveillance. Only syncope, and possibly skin infections were associated with vaccination in the postlicensure setting. Serious adverse events, such as adverse pregnancy outcomes, autoimmune diseases (including Guillain-Barre Syndrome and multiple sclerosis), anaphylaxis, venous thromboembolism and stroke, were extensively studied, and no increase in the incidence of these events was found compared with background rates. Conclusions: These results, along with the safety data from the prelicensure clinical trials, confirm that the HPV4 vaccine has a favorable safety profile. Key policy, medical and regulatory organizations around the world have independently reviewed these data and continue to recommend routine HPV vaccination. Copyright © 2015 Wolters Kluwer Health, Inc.

Introduction Since 2007, many countries have implemented national human papillomavirus (HPV) vaccination programs with the quadrivalent HPV (4HPV) vaccine that has been shown to be efficacious in clinical trials involving 25,000 subjects. Two vaccine serotypes, HPV16 and 18, are responsible for cervical cancer and other HPV-related cancers, but the impact of the 4HPV vaccine on these cancers cannot be seen immediately as there is a considerable lag between infection with HPV and cancer development. The other two serotypes, HPV6 and 11, are responsible for genital warts (GWs), which develop within a few months after infection, making GWs an early clinical endpoint for the assessment of the impact of 4HPV vaccination. Methods We performed a systematic literature search in PubMed to identify all published studies on 4HPV vaccination, including those that assessed the impact of 4HPV vaccination programs on the incidence of GWs at a population level around the world. Results A total of 354 records were identified in the PubMed search. After screening and obtaining full papers for 56 publications, 16 publications presenting data on the impact or effectiveness of 4HPV vaccination on GWs were identified. These reported data on the impact or effectiveness of 4HPV in six countries [Australia (n = 6), New Zealand (n = 2), United States (n = 3), Denmark (n = 2), Germany (n = 1), and Sweden (n = 2)]. In Australia, no GWs were diagnosed in women aged

Tissue microdissection is potentially one of the most useful techniques in molecular pathology. Laser-assisted microdissection has been developed to procure precisely the cells of interest in a tissue specimen, in a rapid and practical manner. Together with multiplex molecular approaches, it is now feasible to study genetic alterations and isolate genes and proteins in defined cell populations from complex normal and diseased tissues. The fundamental advantage of this technique is the possibility of capturing single cells from which high-quality DNA and mRNA can be isolated for analysis of sequence and quantitation of expression. Moreover, the integration of laser-assisted microdissection and proteomic analysis could identify novel protein markers for disease. The advent of laser-assisted microdissection is likely to have a profound impact on molecular pathology.

The biochemical and molecular basis of chlorophyll (Chl) catabolism in bananas was investigated during ripening at 20°C and at an elevated temperature (35°C) where degreening is inhibited. Biochemical analysis showed that Chl breakdown products could be isolated from fruit ripened at both temperatures. The coloured breakdown products, chlorophyllide and pheophorbide, were not detected at any stage of ripening in the two treatments; however, a non-fluorescent Chl catabolite accumulated to a higher concentration at 20 than at 35°C. To investigate the ripening-related gene expression associated with these changes, a cDNA library was generated from the peel of fruit ripened at 20°C. Differential screening of this library produced 20 non-redundant families of clones including those encoding enzymes involved in ethylene biosynthesis, respiration, starch metabolism, cell wall degradation and other metabolic events. The expression of these genes was followed by northern analysis in fruit ripened at 20 and 35°C.

International audience; We report here a targeting method that exploits the expression pattern of cell surface proteases to induce gene delivery to specific tissues. We describe retroviral vectors harboring modified surface glycoproteins derived from an avian influenza virus hemagglutinin (HA) for which the cell entry properties, dependent on HA cleavage by producer cells, were conditionally blocked at a postbinding step by insertion of matrix metalloproteinase (MMP) substrates. We demonstrate that such vectors induce gene transfer, both in vitro and in mice harboring human tumor xenografts, only through contact with target cells expressing MMPs that cleave the substrate introduced into the recombinant HA. This selective gene transfer in MMP-rich cells was specifically inhibited by 1,10-phenanthroline, a broad-range MMP inhibitor. Importantly, such MMP-activatable vectors selectively transduced MMP-rich cells in heterogeneous populations containing MMP-rich and MMP-poor cells. These vectors will allow useful gene transfer applications into target cells exhibiting specific protease activities.

Virus-like particle (VLP)-based vaccines have provided highly encouraging results in clinical trials while, in contrast, DNA vaccines expressing non-particulate proteins have proven less successful. Seeking to combine the immunogenicity of VLPs and the ease of production of plasmid DNA, we designed DNA vaccines expressing VLPs consisting of the MLV Gag and modified MLV Env proteins displaying T cell epitopes. We show here that such DNA vaccines are remarkably efficient immunogens for inducing cellular immune responses. In contrast to similar plasmids harboring a point mutation preventing VLP formation, they induce protection against a lethal viral challenge in mice. Thus, these "plasmo-retroVLPs" represent a promising second-generation DNA vaccine.