The Vaccine and Cervical Cancer Screen project 2 (VACCS 2): Linking cervical cancer screening to a two-dose HPV vaccination schedule in the South-West District of Tshwane, Gauteng, South Africa

Background. Cervical cancer is a preventable disease with a high prevalence in South Africa (SA), where screening is opportunistic. Primary prevention is now possible through HPV vaccination. In VACCS 1 the feasibility of linking cervical cancer with HPV vaccination was demonstrated.Objectives. To investigate the feasibility of linking HPV self-testing with a two-dose HPV vaccination schedule and to compare results with VACCS 1.Methods. The project was conducted in five schools in the South-West District of Tshwane, Gauteng, SA. Leaflet information on cervical cancer and screening was provided, with requests for consent and assent for a two-dose HPV vaccination of schoolgirls. Female caregivers were invited to take part in HPV self-screening.Results. Of 965 girls invited for vaccination, 519 (53.7%) had full consent and 518 (99.8%) received at least one vaccine dose. The invited uptake rate was 53.7% and 495 girls received both doses, giving a completion rate of 95.4% v. 82.6% in VACCS 1. Of 1 135 self-screen kits handed out, 560 (49.3%) were not returned. The mean age (standard deviation) of the 160 women who participated in self-screening was 38.7 (7.7) years. HPV testing was negative in 116 women (72.5%), 15 women (9.4%) tested positive for HPV 16 and/or 18, and 27 (16.9%) were positive for non-16/18 oncogenic HPV.Conclusion. Data from the VACCS projects suggest that school-based vaccine programmes can be successfully implemented. A two-dose schedule allowed for higher completion rates. Linking self-collected HPV screening to HPV vaccination is feasible, is a promising and viable screening strategy, and reached the appropriate age group for screening

The Vaccine and Cervical Cancer Screen project 2 (VACCS 2) : linking cervical cancer screening to a two-dose HPV vaccination schedule in the South-West District of Tshwane, Gauteng, South Africa

CITATION: Snyman, L. C., et al. 2015. The Vaccine and Cervical Cancer Screen project 2 (VACCS 2) : linking cervical cancer screening to a two-dose HPV vaccination schedule in the South-West District of Tshwane, Gauteng, South Africa. South African Medical Journal, 105(3):191-194, doi:10.7196/SAMJ.8888.The original publication is available at http://www.samj.org.zaBackground. Cervical cancer is a preventable disease with a high prevalence in South Africa (SA), where screening is opportunistic. Primary prevention is now possible through HPV vaccination. In VACCS 1 the feasibility of linking cervical cancer with HPV vaccination was demonstrated. Objectives. To investigate the feasibility of linking HPV self-testing with a two-dose HPV vaccination schedule and to compare results with VACCS 1. Methods. The project was conducted in five schools in the South-West District of Tshwane, Gauteng, SA. Leaflet information on cervical cancer and screening was provided, with requests for consent and assent for a two-dose HPV vaccination of schoolgirls. Female caregivers were invited to take part in HPV self-screening. Results. Of 965 girls invited for vaccination, 519 (53.7%) had full consent and 518 (99.8%) received at least one vaccine dose. The invited uptake rate was 53.7% and 495 girls received both doses, giving a completion rate of 95.4% v. 82.6% in VACCS 1. Of 1 135 self-screen kits handed out, 560 (49.3%) were not returned. The mean age (standard deviation) of the 160 women who participated in self-screening was 38.7 (7.7) years. HPV testing was negative in 116 women (72.5%), 15 women (9.4%) tested positive for HPV 16 and/or 18, and 27 (16.9%) were positive for non-16/18 oncogenic HPV. Conclusion. Data from the VACCS projects suggest that school-based vaccine programmes can be successfully implemented. A two-dose schedule allowed for higher completion rates. Linking self-collected HPV screening to HPV vaccination is feasible, is a promising and viable screening strategy, and reached the appropriate age group for screening.AFRIKAANSE OPSOMMING: Geen opsomming beskikbaarhttp://www.samj.org.za/index.php/samj/article/view/8888/Publisher's versio

Phase I of the DiaVACCS screening trial : study design, methods, population demographics and baseline results

BACKGROUND. Human papillomavirus (HPV)-based primary screening guidelines are based on screening test performance and prevalence data generated in high-resource areas with low HIV infection rates. There is an urgent need for local data on infection and disease prevalence, as well as screening test performance, among both HIV-positive and HIV-negative South African (SA) women, in order to inform updated screening guidelines. OBJECTIVES. This study describes the baseline characteristics of participants in the cross-sectional phase of the multicentric DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) screening trial. The objective was to determine the prevalence of positive screening and pre-invasive disease using different tests and strategies in the SA HIV-positive and HIV-negative population. METHODS. A total of 1 104 women aged 25 - 65 years and eligible for screening were included, 465 HIV positive and 639 HIV negative. Visual inspection and molecular and cytological screening tests were done on self-sampled and healthcare worker-collected specimens. All participants who screened positive and 49.1% of those who screened negative were invited for colposcopy and biopsy, and those qualifying for treatment were recalled for large loop excision of the transformation zone as part of the trial. The worst histology result for each participant was used, and for untested women, multiple imputation was used to estimate verification biasadjusted histology values. RESULTS. Visual inspection was positive in 50.4% of HIV-positive v. 20.9% of HIV-negative women, cytology (atypical squamous cells of undetermined significance) in 39.9% v. 17.0%, and high-risk HPV DNA in 41.2% v. 19.6%. Overall, high-grade squamous intraepithelial lesion-positive cytology peaked in the age group 30 - 39 years at 16.7%. After adjustment for verification bias, histological diagnosis of cervical intraepithelial neoplasia (CIN)2+ was suspected in 44.7% v. 23.5% and CIN3+ in 23.3% v. 10.2% of HIV-positive and negative women, respectively. Invasive cancer was diagnosed in 15 women (1.95% of histological studies performed), and verification bias adjustment suggested 20 cases (1.8% of the study population). CONCLUSION. The baseline findings from the DiaVACCS trial confirm a high prevalence of HPV-related cervical pathology in the SA HIV-negative screening population, showing a clear need to reach these women with a screening programme. Among HIV-positive women, prevalence values were almost doubled. The prevalence of existing invasive cervical cancer was 1 - 2% of all women. Further analysis of the performance of single and multiple screening tests between the two subgroups will contribute to the choice of the most effective strategies to identify women at risk of developing invasive cancer.http://www.samj.org.zadm2022Medical VirologyObstetrics and Gynaecolog

Generalized glycogen storage and cardiomegaly in a knockout mouse model of Pompe disease

Glycogen storage disease type II (GSDII; Pompe disease), caused by inherited deficiency of acid alpha-glucosidase, is a lysosomal disorder affecting heart and skeletal muscles. A mouse model of this disease was obtained by targeted disruption of the murine acid alpha-glucosidase gene (Gaa) in embryonic stem cells. Homozygous knockout mice (Gaa -/-) lack Gaa mRNA and have a virtually complete acid alpha-glucosidase deficiency. Glycogen-containing lysosomes are detected soon after birth in liver, heart and skeletal muscle cells. By 13 weeks of age, large focal deposits of glycogen have formed. Vacuolar spaces stain positive for acid phosphatase as a sign of lysosomal pathology. Both male and female knockout mice are fertile and can be intercrossed to produce progeny. The first born knockout mice are at present 9 months old. Overt clinical symptoms are still absent, but the heart is typically enlarged and the electrocardiogram is abnormal. The mouse model will help greatly to understand the pathogenic mechanism of GSDII and is a valuable instrument to explore the efficacy of different therapeutic interventions

Unwanted sex due to intoxication among Australians aged 16–69 years

Intoxication can be a factor in unwanted sex, but research on the extent of the issue in both women and men is limited. We assessed the prevalence, correlates, and 10-year time-trends of unwanted sex due to intoxication among a representative sample of 4,279 women and 3,875 men aged 16–69 years in Australia and considered how these vary by gender. In 2012–13, 16% of women and 10% of men reported ever having had a sexual experience when they “did not want to because they were too drunk or high at the time.” For both women and men, this was associated with younger age, bisexual activity, and reports of lifetime injection drug use, sexually transmitted infections, and forced sex. Among women only, it was associated with drinking above guideline levels and ever having terminated a pregnancy. Among men only, it was associated with current tobacco smoking, elevated psychosocial distress, and poor general health. Compared with 2001–02 data, fewer men reported unwanted intoxicated sex, while there were no changes for women as a whole. Interpreting these findings through an intersectional assemblage framework supports stronger understanding of the multiple factors influencing sexuality and substance use with implications for promoting equity, safety, and sexual health

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Diagnostic accuracy of post-mortem CT with targeted coronary angiography versus autopsy for coroner-requested post-mortem investigations: a prospective, masked, comparison study.

England and Wales have one of the highest frequencies of autopsy in the world. Implementation of post-mortem CT (PMCT), enhanced with targeted coronary angiography (PMCTA), in adults to avoid invasive autopsy would have cultural, religious, and potential economic benefits. We aimed to assess the diagnostic accuracy of PMCTA as a first-line technique in post-mortem investigations.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site

Rare coding variants and X-linked loci associated with age at menarche.

More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 × 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 × 10(-13)) and FAAH2 (rs5914101, P=4.9 × 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P=2.8 × 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.UK sponsors (see article for overseas ones): This work made use of data and samples generated by the 1958 Birth Cohort (NCDS). Access to these resources was enabled via the 58READIE Project funded by Wellcome Trust and Medical Research Council (grant numbers WT095219MA and G1001799). A full list of the financial, institutional and personal contributions to the development of the 1958 Birth Cohort Biomedical resource is available at http://www2.le.ac.uk/projects/birthcohort. Genotyping was undertaken as part of the Wellcome Trust Case-Control Consortium (WTCCC) under Wellcome Trust award 076113, and a full list of the investigators who contributed to the generation of the data is available at www.wtccc.org.uk ... The Fenland Study is funded by the Wellcome Trust and the Medical Research Council, as well as by the Support for Science Funding programme and CamStrad. ... SIBS - CRUK ref: C1287/A8459 SEARCH - CRUK ref: A490/A10124 EMBRACE is supported by Cancer Research UK Grants C1287/A10118, C1287/A16563 and C1287/A17523. Genotyping was supported by Cancer Research - UK grant C12292/A11174D and C8197/A16565. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. ... Generation Scotland - Scottish Executive Health Department, Chief Scientist Office, grant number CZD/16/6. Exome array genotyping for GS:SFHS was funded by the Medical Research Council UK. 23andMe - This work was supported in part by NIH Award 2R44HG006981-02 from the National Human Genome Research Institute.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/ncomms875

Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P=5.4×10−60) and 9q31.2 (P=2.2×10−33), we identified 30 novel menarche loci (all P<5×10−8) and found suggestive evidence for a further 10 loci (P<1.9×10−6). New loci included four previously associated with BMI (in/near FTO, SEC16B, TRA2B and TMEM18), three in/near other genes implicated in energy homeostasis (BSX, CRTC1, and MCHR2), and three in/near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and MAGENTA pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing