114 research outputs found

    Simple models of the chemical field around swimming plankton

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    Background. Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods. Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13 858 healthy controls of European decent. Results. The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10−9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10−8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10−9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10−5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions. Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism

    Defining the genetic susceptibility to cervical neoplasia - a genome-wide association study

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    Funding: MAB was funded by a National Health and Medical Research Council (Australia) Senior Principal Research Fellowship. Support was also received from the Australian Cancer Research Foundation. JL holds a Tier 1 Canada Research Chair in Human Genome Epidemiology. The Seattle study was supported by the following grants: NIH, National Cancer Institute grants P01CA042792 and R01CA112512. Cervical Health Study (from which the NSW component was obtained) was funded by NHMRC Grant 387701, and CCNSW core grant. The Montreal study was funded by the Canadian Institutes of Health Research (grant MOP-42532) and sample processing was funded by the Reseau FRQS SIDA-MI. The Swedish Research Council, the Swedish Foundation for Strategic Research, the ALF/LUA research grant in Gothenburg and Umeå, the Lundberg Foundation, the Torsten and Ragnar Soderberg’s Foundation, the Novo Nordisk Foundation, and the European Commission grant HEALTH-F2-2008-201865-GEFOS, BBMRI.se, the Swedish Society of Medicine, the KempeFoundation (JCK-1021), the Medical Faculty of Umeå University, the County Council of Vasterbotten (Spjutspetsanslag VLL:159:33-2007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PDFPublisher PD

    Epidemiology of HPV genotypes in Uganda and the role of the current preventive vaccines: A systematic review

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    <p>Abstract</p> <p>Background</p> <p>Limited data are available on the distribution of human papillomavirus (HPV) genotypes in the general population and in invasive cervical cancer (ICC) in Uganda. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18 responsible for causing about 70% of ICC cases in the world, such information is crucial to predict how vaccination and HPV-based screening will influence prevention of ICC.</p> <p>Methods</p> <p>To review the distribution of HPV infection and prevalent genotypes, electronic databases (e.g. PubMed/MEDLINE and HINARI) were searched for peer reviewed English articles on HPV infection up to November 30, 2010. Eligible studies were selected according to the following criteria: DNA-confirmed cervical or male genital HPV prevalence and genotypes, HPV incidence estimates and HPV seroprevalence among participants.</p> <p>Results</p> <p>Twenty studies were included in the review. Among HIV negative adult women, the prevalence of HR-HPV infections ranged from 10.2% -40.0% compared to 37.0% -100.0% among HIV positive women. Among HIV positive young women aged below 25 years, the prevalence of HR-HPV genotypes ranged from 41.6% -75.0% compared to 23.7% -67.1% among HIV negative women. Multiple infections with non vaccine HR-HPV genotypes were frequent in both HIV positive and HIV negative women. The main risk factors for prevalent HPV infections were age, lifetime number of sexual partners and HIV infection. Incident infections with HR-HPV genotypes were more frequent among adult HIV positive than HIV negative women estimated at 17.3 and 7.0 per 100 person-years, respectively. Similarly, incident HR-HPV among young women aged below 25 years were more frequent among HIV positive (40.0 per 100 person-years) than HIV negative women (20.3 per 100 person-years) women. The main risk factor for incident infection was HIV infection. HPV 16 and 18 were the most common genotypes in ICC with HPV 16/18 contributing up to 73.5% of cases with single infections.</p> <p>Among uncircumcised adult HIV positive males, HR-HPV prevalence ranged from 55.3% -76.6% compared to 38.6% -47.6% in HIV negative males. Incident and multiple HR-HPV infections were frequent in HIV positive males. Being uncircumcised was the main risk factor for both prevalent and incident HPV infection.</p> <p>Conclusion</p> <p>Infections with HR-HPV genotypes were very common particularly among HIV positive individuals and young women irrespective of HIV status. Given the high prevalence of HIV infection, HPV-associated conditions represent a major public health burden in Uganda. However, although the most common HPV genotypes in ICC cases in Uganda were those targeted by current preventive vaccines, there were a large number of individuals infected with other HR-HPV genotypes. Technology allowing, these other HR-HPV types should be considered in the development of the next generation of vaccines.</p

    Frequency of Chlamydia trachomatis infection in cervical intraepithelial lesions and the status of cytological p16/Ki-67 dual-staining

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    Background: Chlamydia trachomatis (Ct) is not a disease subject to mandatory reporting in Brazil, and the prevalence rate of this genital infection varies according to the region in which studies are conducted, as well as by the detection technique employed. Ct has been associated with persistence of Human papillomavirus (HPV) infection and the facilitation of cervical carcinoma development. We evaluated the Chlamydia trachomatis infection and its association with cytology, p16/Ki-67 dual-stained cytology and cervical intraepithelial lesions status in a screening cohort in Brazil. Methods: This was a cross-sectional study of 1481 cervical samples from asymptomatic women aged 18 to 64. Samples were collected for liquid-based cytology and Ct detection by polymerase chain reaction. p16/Ki-67 double staining was performed on samples with abnormal cytology. Statistical analysis was by chi-square and likelihood-ratio tests. Odds ratio (OR) and 95% confidence intervals (95% CI) were determined. Results: The frequency of Ct was 15.6% and its presence was not associated with detection of p16/Ki-67 [OR = 1. 35 (0.5-3.4)]. There was also no association between abnormal cervical cytology and Ct-positivity [OR = 1.21 (0.46-3.2)]. Associations were observed between p16/Ki-67 and high-grade lesions detected by cytology and in biopsies [OR = 3.55 (1.50-8.42) and OR = 19.00 (0.6-7.2), respectively]. Conclusions: The asymptomatic women in our study had a high frequency of Ct infection but this was not associated with p16/Ki-67 detection in samples with abnormal cytology. The expression of p16/Ki-67 was highest in women with high-grade CIN (p = 0.003).info:eu-repo/semantics/publishedVersio

    Phase I Randomised Clinical Trial of an HIV-1CN54, Clade C, Trimeric Envelope Vaccine Candidate Delivered Vaginally

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    We conducted a phase 1 double-blind randomised controlled trial (RCT) of a HIV-1 envelope protein (CN54 gp140) candidate vaccine delivered vaginally to assess immunogenicity and safety. It was hypothesised that repeated delivery of gp140 may facilitate antigen uptake and presentation at this mucosal surface. Twenty two healthy female volunteers aged 18–45 years were entered into the trial, the first receiving open-label active product. Subsequently, 16 women were randomised to receive 9 doses of 100 µg of gp140 in 3 ml of a Carbopol 974P based gel, 5 were randomised to placebo solution in the same gel, delivered vaginally via an applicator. Participants delivered the vaccine three times a week over three weeks during one menstrual cycle, and were followed up for two further months. There were no serious adverse events, and the vaccine was well tolerated. No sustained systemic or local IgG, IgA, or T cell responses to the gp140 were detected following vaginal immunisations. Repeated vaginal immunisation with a HIV-1 envelope protein alone formulated in Carbopol gel was safe, but did not induce local or systemic immune responses in healthy women

    Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies.

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    The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose
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