Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 4-year interim follow-up of the phase 3, double-blind, randomised controlled VIVIANE study
Skinner S.R.,University of Sydney |
Szarewski A.,Queen Mary, University of London |
Romanowski B.,University of Alberta |
Garland S.M.,Royal Womens Hospital |
And 28 more authors.
The Lancet | Year: 2014
Background Although adolescent girls are the main population for prophylactic human papillomavirus (HPV) vaccines, adult women who remain at risk of cervical cancer can also be vaccinated. We report data from the interim analysis of the ongoing VIVIANE study, the aim of which is to assess the efficacy, safety, and immunogenicity of the HPV 16/18 AS04-adjuvanted vaccine in adult women. Methods In this phase 3, multinational, double-blind, randomised controlled trial, we randomly assigned healthy women older than 25 years to the HPV 16/18 vaccine or control (1:1), via an internet-based system with an algorithm process that accounted for region, age stratum, baseline HPV DNA status, HPV 16/18 serostatus, and cytology. Enrolment was age-stratified, with about 45% of participants in each of the 26-35 and 36-45 years age strata and 10% in the 46 years and older stratum. Up to 15% of women in each age stratum could have a history of HPV infection or disease. The primary endpoint was vaccine efficacy against 6-month persistent infection or cervical intraepithelial neoplasia grade 1 or higher (CIN1+) associated with HPV 16/18. The primary analysis was done in the according-to-protocol cohort for efficacy, which consists of women who received all three vaccine or control doses, had negative or low-grade cytology at baseline, and had no history of HPV disease. Secondary analyses included vaccine efficacy against non-vaccine oncogenic HPV types. Mean follow-up time was 40·3 months. This study is registered with ClinicalTrials.gov, number NCT00294047. Findings The first participant was enrolled on Feb 16, 2006, and the last study visit for the present analysis took place on Dec 10, 2010; 5752 women were included in the total vaccinated cohort (n=2881 vaccine, n=2871 control), and 4505 in the according-to-protocol cohort for efficacy (n=2264 vaccine, n=2241 control). Vaccine efficacy against HPV 16/18-related 6-month persistent infection or CIN1+ was significant in all age groups combined (81·1%, 97·7% CI 52·1-94·0), in the 26-35 years age group (83·5%, 45·0-96·8), and in the 36-45 years age group (77·2%, 2·8-96·9); no cases were seen in women aged 46 years and older. Vaccine efficacy against atypical squamous cells of undetermined significance or greater associated with HPV 16/18 was also significant. We also noted significant cross-protective vaccine efficacy against 6-month persistent infection with HPV 31 (79·1%, 97·7% CI 27·6-95·9) and HPV 45 (76·9%, 18·5-95·6]) Serious adverse events occurred in 285 (10%) of 2881 women in the vaccine group and 267 (9%) of 2871 in the control group; five (<1%) and eight (<1%) of these events, respectively, were believed to be related to vaccination. Interpretation In women older than 25 years, the HPV 16/18 vaccine is efficacious against infections and cervical abnormalities associated with the vaccine types, as well as infections with the non-vaccine HPV types 31 and 45. Funding GlaxoSmithKline Biologicals SA. © 2014 Elsevier Ltd. All rights reserved.
Self-collection based HPV testing for cervical cancer screening among women living with HIV in Uganda: a descriptive analysis of knowledge, intentions to screen and factors associated with HPV positivity
PubMed | University of British Columbia, Oak Street Health, Kisenyi Health Center, Makerere University and Womens Health Research Institute
Type: Journal Article | Journal: BMC women's health | Year: 2017
Women living with HIV (WHIV) are disproportionately impacted by cervical dysplasia and cancer. The burden is greatest in low-income countries where limited or no access to screening exists. The goal of this study was to describe knowledge and intentions of WHIV towards HPV self-collection for cervical cancer screening, and to report on factors related to HPV positivity among women who participated in testing.A validated survey was administered to 87 HIV positive women attending the Kisenyi Health Unit aged 30-69 years old, and data was abstracted from chart review. At a later date, self-collection based HPV testing was offered to all women. Specimens were tested for high risk HPV genotypes, and women were contacted with results and referred for care. Descriptive statistics, Chi Square and Fischer-exact statistical tests were performed.The vast majority of WHIV (98.9%) women did not think it necessary to be screened for cervical cancer and the majority of women had never heard of HPV (96.4%). However, almost all WHIV found self-collection for cervical cancer screening to be acceptable. Of the 87 WHIV offered self-collection, 40 women agreed to provide a sample at the HIV clinic. Among women tested, 45% were oncogenic HPV positive, where HPV 16 or 18 positivity was 15% overall.In this group of WHIV engaged in HIV care, there was a high prevalence of oncogenic HPV, a large proportion of which were HPV genotypes 16 or 18, in addition to low knowledge of HPV and cervical cancer screening. Improved education and cervical cancer screening for WHIV are sorely needed; self-collection based screening has the potential to be integrated with routine HIV care in this setting.
Chaban B.,University of Saskatchewan |
Albert A.,Womens Health Research Institute |
Links M.G.,University of Saskatchewan |
Links M.G.,Saskatoon Research Center |
And 4 more authors.
PLoS ONE | Year: 2013
The upper respiratory tract microbiome has an important role in respiratory health. Influenza A is a common viral infection that challenges that health, and a well-recognized sequela is bacterial pneumonia. Given this connection, we sought to characterize the upper respiratory tract microbiota of individuals suffering from the pandemic H1N1 influenza A outbreak of 2009 and determine if microbiome profiles could be correlated with patient characteristics. We determined the microbial profiles of 65 samples from H1N1 patients by cpn60 universal target amplification and sequencing. Profiles were examined at the phylum and nearest neighbor "species" levels using the characteristics of patient gender, age, originating health authority, sample type and designation (STAT/non-STAT). At the phylum level, Actinobacteria-, Firmicutes- and Proteobacteria-dominated microbiomes were observed, with none of the patient characteristics showing significant profile composition differences. At the nearest neighbor "species" level, the upper respiratory tract microbiomes were composed of 13-20 "species" and showed a trend towards increasing diversity with patient age. Interestingly, at an individual level, most patients had one to three organisms dominant in their microbiota. A limited number of discrete microbiome profiles were observed, shared among influenza patients regardless of patient status variables. To assess the validity of analyses derived from sequence read abundance, several bacterial species were quantified by quantitative PCR and compared to the abundance of cpn60 sequence read counts obtained in the study. A strong positive correlation between read abundance and absolute bacterial quantification was observed. This study represents the first examination of the upper respiratory tract microbiome using a target other than the 16S rRNA gene and to our knowledge, the first thorough examination of this microbiome during a viral infection. © 2013 Chaban et al.
Kaida A.,Simon Fraser University |
Laher F.,University of Witwatersrand |
Strathdee S.A.,University of California at San Diego |
Money D.,Womens Health Research Institute |
And 6 more authors.
PLoS ONE | Year: 2010
Objective: Preventing unintended pregnancy among HIV-positive women constitutes a critical and cost-effective approach to primary prevention of mother-to-child transmission of HIV and is a global public health priority for addressing the desperate state of maternal and child health in HIV hyper-endemic settings. We sought to investigate whether the prevalence of contraceptive use and method preferences varied by HIV status and receipt of highly active antiretroviral therapy (HAART) among women in Soweto, South Africa. Methods: We used survey data from 563 sexually active, non-pregnant women (18-44 years) recruited from the Perinatal HIV Research Unit in Soweto (May-December, 2007); 171 women were HIV-positive and receiving HAART (median duration of use = 31 months; IQR = 28, 33), 178 were HIV-positive and HAART-naïve, and 214 were HIV-negative. Medical record review was conducted to confirm HIV status and clinical variables. Logistic regression models estimated adjusted associations between HIV status, receipt of HAART, and contraceptive use. Results: Overall, 78% of women reported using contraception, with significant variation by HIV status: 86% of HAART users, 82% of HAART-naïve women, and 69% of HIV-negative women (p<0.0001). In adjusted models, compared with HIVnegative women, women receiving HAART were significantly more likely to use contraception while HAART-naïve women were non-significantly more likely (AOR: 2.40; 95% CI: 1.25, 4.62 and AOR: 1.59; 95% CI: 0.88, 2.85; respectively). Among HIVpositive women, HAART users were non-significantly more likely to use contraception compared with HAART-naïve women (AOR: 1.55; 95% CI: 0.84, 2.88). Similar patterns held for specific use of barrier (primarily male condoms), permanent, and dual protection contraceptive methods. Conclusion: Among HIV-positive women receiving HAART, the observed higher prevalence of contraceptive use overall and condoms in particular promises to yield fewer unintended pregnancies and reduced risks of vertical and sexual HIV transmission. These findings highlight the potential of integrated HIV and reproductive health services to positively impact maternal, partner, and child health. © 2010 Kaida et al.
Powell C.B.,Kaiser Permanente |
Littell R.,Kaiser Permanente |
Hoodfar E.,Northern California Regional Genetics Program |
Sinclair F.,Womens Health Research Institute |
Pressman A.,Kaiser Permanente
International Journal of Gynecological Cancer | Year: 2013
Kaiser Permanente Northern California is a large integrated health care delivery system in the United States that has guidelines for referring women with newly diagnosed BRCA1-and BRCA2-associated cancers for genetic counseling. This study assesses adherence to genetic counseling referral guidelines within this health system. Methods: Chart review was performed to identify patients with cancer who met the following pathology-based Kaiser Permanente Northern California guidelines for referral for genetic counseling: invasive breast cancer, younger than age 40; nonmucinous epithelial ovarian, fallopian tube, or peritoneal cancer, younger than age 60; women with synchronous or metachronous primary cancers of the breast and ovaries; and male breast cancer. We assessed compliance with referral guidelines. An electronic notice was sent to the managing physician of patients with newly diagnosed cancer to assess the feasibility of this intervention. Results: A total of 340 patientswere identified with breast cancer at younger than age 40 or with ovarian, peritoneal, or tubal cancer between January and June, 2008. Upon chart review, 105 of these patients met pathology-based criteria for referral to genetic counseling, of whom 47 (45%) were referred within the 2-year study period. Of the 67 subjects with breast cancer, 40 subjects (60%) were referred. In contrast, only 7 (21%) of 33 patients with ovarian cancer were referred (P < 0.001). A pilot study was performed to test the feasibility of notifying managing oncologists with an electronic letter alerting them of eligibility for genetic referral of patients with new diagnosis (n = 21). In the 3 to 6 months after this notification, 12 of these 21 patients were referred for counseling including 5 of 7 patients with a diagnosis of ovarian cancer. Conclusion: There is a missed opportunity for referring patients to genetic counseling, especially among patients with ovarian cancer. A pilot study suggests that alerting treating physicians is a feasible strategy to increase appropriate referral. © 2013 by IGCS and ESGO.
Loane H.,University of British Columbia |
Preston R.,University of British Columbia |
Douglas M.J.,University of British Columbia |
Massey S.,University of British Columbia |
And 2 more authors.
International Journal of Obstetric Anesthesia | Year: 2012
Background: Intrathecal morphine is an effective analgesic post-cesarean delivery; however, it may be contraindicated or unsuitable in some patients. We compared the efficacy and side effects of intrathecal morphine with an ultrasound-guided transversus abdominis plane (TAP) block in a randomized, controlled, double-blinded trial. The primary outcome was the morphine equivalents dose used in the first 24 h post-surgery. Secondary outcomes were pain scores and side effects, including pruritus, sedation, nausea and vomiting. Methods: Planned recruitment was for 90 women; however, the study was terminated early. Sixty-nine women undergoing elective cesarean delivery under spinal anesthesia were enrolled. They were randomized to receive either intrathecal morphine 100 μg plus a sham TAP block or a TAP block with 0.5% ropivacaine 1.5 mg/kg, to each side to a maximum of 20 mL. Women were assessed at 2, 6, 10, 24 h and 3 months post-spinal. Results: Sixty-six women completed the trial. The morphine equivalents dose used in the TAP block group was greater at 24 h compared with the intrathecal morphine group (7.5 mg (95% CI 4.8-10.2) vs. 2.7 mg (95% CI 1.0-4.3), F [1, 64] = 9.62, P = 0.003). There was no difference at 2, 6, or 10 h. Pain scores on rest and movement were higher in the TAP block group at all times although this only reached statistical significance at 10 h (P = 0.001). Nausea and vomiting (P = 0.02) and pruritus (P = 0.007) were lower in the TAP block group. Conclusions: In this trial, the TAP block was associated with greater supplemental morphine requirements and higher pain scores than intrathecal morphine but fewer opioid-related side effects. The TAP block may be a reasonable alternative when intrathecal morphine is contraindicated or not appropriate. © 2012 Elsevier Ltd. All rights reserved.
Salmon A.,Womens Health Research Institute |
Salmon A.,University of British Columbia
Critical Public Health | Year: 2011
Over the past 25 years, Aboriginal leaders, community advocates, children's and women's health specialists and Canadian government agencies have drawn increasing attention to the perceived need to undertake targeted initiatives to prevent fetal alcohol spectrum disorder (FASD) in indigenous communities. In pursuit of this goal, a range of prevention campaigns have been undertaken - generally with funding from the State - urging pregnant women to abstain from alcohol. Because both risk and protective factors for FASD are intimately connected to the social conditions in which women become pregnant, give birth to and mother their children, FASD prevention campaigns targeting Aboriginal communities suggest possibilities that are both provocative and problematic for advancing movements for social justice, decolonisation and improved maternal and child health. In this essay, I consider how the gendered and racialised legacies of colonisation emerge alongside concerns for improved health and well-being of indigenous children to inform contemporary, state-funded efforts to prevent FASD. In so doing, I examine the ways that neoliberal economic and political trajectories of Canadian state formation intersect with some aspects of decolonisation movements to raise important questions about when, how and under what conditions colonial states support FASD prevention efforts among indigenous peoples. © 2011 Taylor & Francis.
Hodgson Z.G.,Womens Health Research Institute |
Abrahams R.R.,Womens Health Research Institute |
Abrahams R.R.,University of British Columbia |
Abrahams R.R.,Womens Hospital and Health Center
Journal of Obstetrics and Gynaecology Canada | Year: 2012
Objective: The purpose of this study was to explore the effect of our rooming-in protocol on the need to treat withdrawal in the opiateexposed newborn. Methods: We reviewed the medical records of mother-infant dyads born between October 1, 2003, and December 31, 2006, who received care in our rooming-in program. Data on the type of drug used by the mother, maternal methadone dose at delivery, morphine treatment of the baby, and perinatal outcome were considered. Results: We found a significant positive relationship between maternal methadone dose at delivery, "other opiate" use, and breastfeeding and the need to treat the neonate for withdrawal. We also found the maternal methadone dose at delivery to be related to the duration of pharmacological treatment of the neonate. Conclusion: Our findings suggest a role for our rooming-in program in mitigating the relationship between maternal methadone dosage and the need to treat opiate withdrawal in the newborn. Consideration of the role played by the mother-infant dyad model of care needs to be considered in future studies. © 2012 Society of Obstetricians and Gynaecologists of Canada.
Riddell L.,Womens Hospital and Health Center |
Varto H.,Vancouver Coastal Health Research Institute |
Hodgson Z.G.,Womens Health Research Institute
Canadian Journal of Human Sexuality | Year: 2010
This exploratory, descriptive study investigated the motivations and practices behind the phenomenon of pubic hair removal among women. A final sample of 660 women aged 16-50 years who had ever removed their pubic hair completed surveys asking about their reasons for, methods of, and side effects associated with this practice. Based on their usual practices for areas of hair removal, bikini line was reported by about 50% of participants and whole pubic area by about 30%. Shaving, salon waxing, and trimming with scissors were the most common usual methods although many more reported having ever tried more than one of these or other methods. Appearance in a bathing suit was the most common reason given for pubic hair removal followed by feeling attractive and by the notion that pubic hair removal is cleaner. Side effects ever experienced were common and included razor bump and ingrown hairs but also rash, pimples, and cuts among other less common types of pubic skin traumatization. Further research is proposed to better understand the social constructs of pubic hair removal and to develop best practice guidelines for health professionals in relation to this phenomenon.
Sklepkiewicz P.,York College |
Shiomi T.,York College |
Kaur R.,York College |
Sun J.,York College |
And 7 more authors.
Circulation: Heart Failure | Year: 2015
Background-The Wnt/β-catenin signaling pathway plays a central role during cardiac development and has been implicated in cardiac remodeling and aging. However, the role of Wnt modulators in this process is unknown. In this study, we examined the role of the Wnt signaling inhibitor secreted frizzled-related protein-1 (sFRP-1) in aged wild-type and sFRP-1-deficient mice. Methods and Results-sFRP-1 gene deletion mice were grossly normal with no difference in mortality but developed abnormal cardiac structure and dysfunction with progressive age. Ventricular dilation and hypertrophy in addition to deterioration of cardiac function and massive cardiac fibrosis, all features present in dilated cardiomyopathy, were observed in the aged sFRP-1 knockout mice. Loss of sFRP-1 led to increased expression of Wnt ligands (Wnt1, 3, 7b, and 16) and Wnt target genes (Wisp1 and Lef1) in aged hearts, which correlated with increased protein levels of β-catenin. Cardiac fibroblasts lacking endogenous sFRP-1 showed increased φ-smooth muscle actin expression, higher cell proliferation rates, and increased collagen production consistent with the cardiac phenotype exhibited in aged sFRP-1 knockout mice. The clinical relevance of these findings was supported by the demonstration of decreased sFRP-1 gene expression and increased Wisp-1 levels in the left ventricles of patients with ischemic dilated cardiomyopathy and dilated cardiomyopathy. Conclusions-This study identifies a novel role of sFRP-1 in age-related cardiac deterioration and fibrosis. Further exploration of this pathway will identify downstream molecules important in these processes and also suggest the potential use of Wnt signaling agents as therapeutic targets for age-related cardiovascular disorders in humans. © 2015 American Heart Associations, Inc.