Efficacy and Safety of Prophylactic Vaccines against Cervical HPV Infection and Diseases among Women: A Systematic Review & MetaAnalysis

Background: We conducted a systematic review and meta-analysis to assess efficacy and safety of prophylactic HPV vaccines against cervical cancer precursor events in women. Methods: Randomized-controlled trials of HPV vaccines were identified from MEDLINE, Cochrane Central Register of Controlled Trials, conference abstracts and references of identified studies, and assessed by two independent reviewers. Efficacy data were synthesized using fixed-effect models, and evaluated for heterogeneity using I-2 statistic. Results: Seven unique trials enrolling 44,142 females were included. The fixed-effect Relative Risk (RR) and 95% confidence intervals were 0.04 (0.01-0.11) and 0.10 (0.03-0.38) for HPV-16 and HPV 18-related CIN2+ in the per-protocol populations (PPP). The corresponding RR was 0.47 (0.36-0.61) and 0.16 (0.08-0.34) in the intention-to-treat populations (ITT). Efficacy against CIN1+ was similar in scale in favor of vaccine. Overall vaccines were highly efficacious against 6-month persistent infection with HPV 16 and 18, both in the PPP cohort (RR: 0.06 [0.04-0.09] and 0.05 [0.03-0.09], respectively), and the ITT cohorts (RR: 0.15 [0.10-0.23] and 0.24 [0.14-0.42], respectively). There was limited prophylactic effect against CIN2+ and 6-month persistent infections associated with non-vaccine oncogenic HPV types. The risk of serious adverse events (RR: 1.00, 0.91-1.09) or vaccine-related serious adverse events (RR: 1.82; 0.79-4.20) did not differ significantly between vaccine and control groups. Data on abnormal pregnancy outcomes were underreported. Conclusions: Prophylactic HPV vaccines are safe, well tolerated, and highly efficacious in preventing persistent infections and cervical diseases associated with vaccine-HPV types among young females. However, long-term efficacy and safety needs to be addressed in future trials

Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies

Age Factors; Anal human papillomavirus infection; SexualityFactores de edad; Infección anal por virus del papiloma humano; SexualidadFactors d'edat; Infecció anal pel virus del papil·loma humà; SexualitatBackground Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality. Methods We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models. Findings The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15–18 years and 28·8% (141 of 490) among those age 23–24 years (ptrend=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25–34 years and 22·8% (451 of 1979) among those age 55 and older (ptrend<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15–18 and 13·9% (166 of 1192) among those age 23–24 years (ptrend=0·0076); the prevalence plateaued thereafter (ptrend=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36–1·73), HPV16-positive HSIL+ (1·66, 1·36–2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04–1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age. Interpretation High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+.International Agency for Research on Cancer

Parental intent to initiate and Complete the Human Papillomavirus Vaccine Series in the Usa: a Nationwide, Cross-Sectional Survey

BACKGROUND: Human papillomavirus (HPV) vaccine uptake among US adolescents is primarily dependent on the intent of their parents. to the best of our knowledge, an analysis quantifying parental intent to initiate and complete the HPV vaccine series in the USA at both the national and state level has not been done. We aim to estimate parental intent to initiate and complete the HPV vaccine series at the national-level and state-level and to identify reasons for lack of intent to initiate and complete the vaccine series. METHODS: This cross-sectional study uses data from the adolescent component of the 2017-18 National Immunization Survey (NIS-Teen). Study participants were parents or caregivers of US adolescents aged 13-17 years, who were most knowledgeable about the immunisation status of the adolescents. The primary outcome was parental intent to vaccinate the adolescent in the next 12 months. The secondary outcomes were (1) the prevalence of reasons given for lack of intent to initiate and complete the HPV vaccine series, and (2) the relationship between receiving a recommendation from a health-care provider to vaccinate and intent to initiate the vaccination series. We computed national-level and state-level estimates for parental lack of intent to initiate and to complete the vaccine series; population-level estimates were derived using survey weights. A survey design-adjusted Wald F test was used for bivariate analysis. A multivariate logistic regression model was used to examine the association between health-care provider recommendation and parental intent to initiate the series. Analyses were stratified by history of health-care provider recommendation to initiate the HPV vaccine series. FINDINGS: In 2017-18, the parent or caregiver of 82 297 US adolescents aged 13-17 years completed the NIS-Teen survey. 30 558 (37·1%) were unvaccinated and 9073 (10·8%) received only one HPV vaccine dose. Parents of 58·0% (17 171/29 086) of unvaccinated adolescents with data available on parental intent had no intention to initiate the HPV vaccine series. More than 65% of parents of unvaccinated adolescents in Idaho, Kansas, Michigan, Montana, Nebraska, North Dakota, Oklahoma, and Utah had no intention to initiate the HPV vaccine series. Parents of 23·5% (2166/9072) of initiators with data available on parental intent had no intention to complete the HPV vaccine series. More than 30% of parents in Arkansas, Florida, Georgia, Hawaii, Idaho, Utah, and West Virginia did not intend to complete the HPV vaccine series, whereas in the District of Columbia (11·2% [22/166]) and Rhode Island (20·4% [21/112]) parental lack of intent was relatively low (both regions have an HPV vaccine mandate). The most common reason for lack of intent among parents to initiate the vaccine for unvaccinated adolescents was safety concerns (22·8% [4182/16 455]); lack of a recommendation from a health-care provider (22·2% [440/1944]) was the most frequently cited reason for absence of intent to complete the series among parents of adolescents who received only one HPV vaccine dose. Receipt of a recommendation from a health-care provider was associated with greater odds of parental intent to initiate the HPV vaccine series (odds ratio 1·11, 95% CI 1·01-1·22). 45·5% (13 156/29 086) of parents of unvaccinated adolescents had reportedly received an HPV vaccine recommendation. Parents of 60·6% (7938/13 156) of unvaccinated adolescents with a recommendation from a health-care provider and data available on parental intent had no intention to initiate the series. INTERPRETATION: Lack of parental intent to initiate and complete the HPV vaccine series for adolescents is a major public health concern in the USA. Combating vaccine safety concerns and strong recommendations from health-care providers could improve the currently suboptimal HPV vaccination coverage. FUNDING: US National Cancer Institute

Molecular markers for analyses of intraspecific genetic diversity in the Asian Tiger mosquito, Aedes albopictus

BACKGROUND: The dramatic worldwide expansion of Aedes albopictus (the Asian tiger mosquito) and its vector competence for numerous arboviruses represent a growing threat to public health security. Molecular markers are crucially needed for tracking the rapid spread of this mosquito and to obtain a deeper knowledge of population structure. This is a fundamental requirement for the development of strict monitoring protocols and for the improvement of sustainable control measures. METHODS: Wild population samples from putative source areas and from newly colonised regions were analysed for variability at the ribosomal DNA internal transcribed spacer 2 (ITS2). Moreover, a new set of 23 microsatellite markers (SSR) was developed. Sixteen of these SSRs were tested in an ancestral (Thailand) and two adventive Italian populations. RESULTS: Seventy-six ITS2 sequences representing 52 unique haplotypes were identified, and AMOVA indicated that most of their variation occurred within individuals (74.36%), while only about 8% was detected among populations. Spatial analyses of molecular variance revealed that haplotype genetic similarity was not related to the geographic proximity of populations and the haplotype phylogeny clearly indicated that highly related sequences were distributed across populations from different geographical regions. The SSR markers displayed a high level of polymorphism both in the ancestral and in adventive populations, and F(ST) estimates suggested the absence of great differentiation. The ancestral nature of the Thai population was corroborated by its higher level of variability. CONCLUSIONS: The two types of genetic markers here implemented revealed the distribution of genetic diversity within and between populations and provide clues on the dispersion dynamics of this species. It appears that the diffusion of this mosquito does not conform to a progressive expansion from the native Asian source area, but to a relatively recent and chaotic propagule distribution mediated by human activities. Under this scenario, multiple introductions and admixture events probably play an important role in maintaining the genetic diversity and in avoiding bottleneck effects. The polymorphic SSR markers here implemented will provide an important tool for reconstructing the routes of invasion followed by this mosquito

Gravure‐Printed Conversion/Alloying Anodes for Lithium‐Ion Batteries

Recently, printing techniques are increasingly investigated in the field of energy storage, especially for the fabrication of custom-designed batteries. Thanks to its many advantages, the most industrially used gravure printing would offer an innovative boost to printed battery production, even if, to date, such a technique is still not well investigated. In this study, for the first time, gravure printing is successfully used to prepare high-performance conversion/alloying anodes for lithium-ion batteries. A multilayer approach allows obtainment of the desired mass loading (about 1.7 mg cm$^{-2}$), reaching similar mass loadings to those obtained by commonly used lab-scale tape-casting methods, allowing for their comparison. High-quality gravure-printed layers are obtained showing a very high homogeneity, resulting in a high reproducibility of their electrochemical performance, very close to the theoretical value, and a long cycle life (up to 400 cycles). The good results are also due to the ink preparation method, using a ball-milling mix of the powders for disaggregation and homogenization of the starting materials. This work demonstrates the possibility of using the highly scalable gravure printing not only in the industrial manufacturing of printed batteries, but also as a useful tool for the study of new materials

Gene discovery in an invasive tephritid model pest species, the Mediterranean fruit fly, Ceratitis capitata

<p>Abstract</p> <p>Background</p> <p>The medfly, <it>Ceratitis capitata</it>, is a highly invasive agricultural pest that has become a model insect for the development of biological control programs. Despite research into the behavior and classical and population genetics of this organism, the quantity of sequence data available is limited. We have utilized an expressed sequence tag (EST) approach to obtain detailed information on transcriptome signatures that relate to a variety of physiological systems in the medfly; this information emphasizes on reproduction, sex determination, and chemosensory perception, since the study was based on normalized cDNA libraries from embryos and adult heads.</p> <p>Results</p> <p>A total of 21,253 high-quality ESTs were obtained from the embryo and head libraries. Clustering analyses performed separately for each library resulted in 5201 embryo and 6684 head transcripts. Considering an estimated 19% overlap in the transcriptomes of the two libraries, they represent about 9614 unique transcripts involved in a wide range of biological processes and molecular functions. Of particular interest are the sequences that share homology with <it>Drosophila </it>genes involved in sex determination, olfaction, and reproductive behavior. The medfly <it>transformer2 </it>(<it>tra2</it>) homolog was identified among the embryonic sequences, and its genomic organization and expression were characterized.</p> <p>Conclusion</p> <p>The sequences obtained in this study represent the first major dataset of expressed genes in a tephritid species of agricultural importance. This resource provides essential information to support the investigation of numerous questions regarding the biology of the medfly and other related species and also constitutes an invaluable tool for the annotation of complete genome sequences. Our study has revealed intriguing findings regarding the transcript regulation of <it>tra2 </it>and other sex determination genes, as well as insights into the comparative genomics of genes implicated in chemosensory reception and reproduction.</p

The content and context of physicians' communication with males about human papillomavirus vaccination

A physician's recommendation for human papillomavirus (HPV) vaccine is a key predictor of vaccine uptake; however, little is known about how physicians communicate about HPV vaccine with male patients. We sought to describe physicians' HPV vaccine communication practices with males who are of vaccine-eligible age (9-26 years). We surveyed representative samples of pediatric and family medicine physicians in Florida, and assessed whether physicians present HPV vaccine as optional or routine, and as a vaccine that prevents cancer. We also assessed the type of visit during which physicians discuss HPV vaccine with adolescent males and whether other healthcare providers in the practice discuss HPV vaccine or make the initial recommendation. We received 367 completed surveys (50.7% response rate). Few physicians (29.9%) reported they typically present HPV vaccine as routine to males ages 11-12 years, who constitute the target group for routine vaccination. When discussing HPV vaccination, many physicians reported somewhat or strongly emphasizing cancer prevention (80.0%). Physicians most often discussed HPV vaccine when they saw patients for well-child visits (93.0%) and least often at acute care visits (15.3%). Over half reported that at least one other healthcare professional in their practice discusses (56.1%) or makes the initial recommendation for (54.9%) HPV vaccination. Many physicians in our sample are presenting HPV vaccine as optional rather than routine and are missing opportunities to communicate with males about the vaccine. Our findings identify areas for future interventions to improve physicians' HPV vaccine communication and, ultimately, increase the use of this cancer-preventing vaccine

Physicians' human papillomavirus vaccine recommendations in the context of permissive guidelines for male patients: a national study

BACKGROUND: Little is known about physicians' human papillomavirus (HPV) vaccine recommendations for males while the Advisory Committee on Immunization Practices' (ACIP) permissive guidelines for male vaccination were in effect. The purpose of this study was to examine and explore factors associated with U.S. physicians' HPV vaccine recommendations to early (ages 11-12), middle (13-17), and late adolescent/young adult (18-26) males. METHODS: Nationally representative samples of family physicians and pediatricians were selected in 2011 (n = 1,219). Physicians reported the frequency with which they recommended HPV vaccine to male patients ["always" (>75% of the time) vs. other] for each age group. Statistically significant predictors of vaccine recommendation were identified using multivariable logistic regression. RESULTS: The prevalence of physicians reporting they "always" recommended HPV vaccination for males was 10.8% for ages 11 to 12, 12.9% for ages 13 to 17, and 13.2% for ages 18 to 26. Pediatrician specialty and self-reported early adoption of new vaccines were significantly associated with recommendation for all patient age groups. In addition, physician race and patient payment method were associated with physician recommendations to patients ages 11 to 12, and patient race was associated with recommendations to ages 13 to 17 and 18 to 26. CONCLUSIONS: Less than 15% of physicians surveyed reported "always" recommending HPV vaccine to male patients following national guidelines for permissive vaccination. Vaccine financing may have affected physicians' vaccine recommendations. IMPACT: If these recommendation practices continue following the ACIP's routine recommendation for males in October 2011, then interventions designed to increase recommendations should target family physicians and possibly use early adopters to encourage support of HPV vaccination guidelines

Sex and the single embryo: early deveopment in the Mediterranean fruit fly, Ceratitis capitata

<p>Abstract</p> <p>Background</p> <p>In embryos the maternal-to-zygotic transition (MTZ) integrates post-transcriptional regulation of maternal transcripts with transcriptional activation of the zygotic genome. Although the molecular mechanisms underlying this event are being clarified in <it>Drosophila melanogaster</it>, little is know about the embryogenic processes in other insect species. The recent publication of expressed sequence tags (ESTs) from embryos of the global pest species <it>Ceratitis capitata </it>(medfly) has enabled the investigation of embryogenesis in this species and has allowed a comparison of the embryogenic processes in these two related dipteran species, <it>C. capitata </it>and <it>D. melanogaster</it>, that shared a common ancestor 80-100 mya.</p> <p>Results</p> <p>Using a novel PCR-based sexing method, which takes advantage of a putative LTR retrotransposon MITE insertion on the medfly Y chromosome, the transcriptomes of individual early male and female embryos were analysed using RT-PCR. This study is focused on two crucial aspects of the onset of embryonic development: sex determination and cellular blastoderm formation. Together with the three known medfly genes (<it>Cctransformer</it>, <it>Cctransformer2 </it>and <it>Ccdoublesex</it>), the expression patterns of other medfly genes that are similar to the <it>D. melanogaster </it>sex-determination genes (<it>sisterlessA, groucho, deadpan, Sex-lethal, female lethal d, sans fille </it>and <it>intersex</it>) and four cellular blastoderm formation genes (<it>Rho1, spaghetti squash, slow-as-molasses </it>and <it>serendipity-α</it>) were analyzed, allowing us to sketch a preliminary outline of the embryonic process in the medfly. Furthermore, a putative homologue of the <it>Zelda </it>gene has been considered, which in <it>D. melanogaster </it>encodes a DNA-binding factor responsible for the maternal-to-zygotic transition.</p> <p>Conclusions</p> <p>Our novel sexing method facilitates the study of i) when the MTZ transition occurs in males and females of <it>C. capitata</it>, ii) when and how the maternal information of "female-development" is reprogrammed in the embryos and iii) similarities and differences in the regulation of gene expression in <it>C. capitata </it>and <it>D. melanogaster</it>. We suggest a new model for the onset of the sex determination cascade in the medfly: the maternally inherited <it>Cctra </it>transcripts in the female embryos are insufficient to produce enough active protein to inhibit the male mode of <it>Cctra </it>splicing. The slow rate of development and the inefficiency of the splicing mechanism in the pre-cellular blastoderm facilitates the male-determining factor (M) activity, which probably acts by inhibiting CcTRA protein activity.</p