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.

Transplanting the elderly: Balancing aging with histocompatibility.

Across the world, the proportions of senior citizens (i.e. those ≥65years) increase rapidly and are predicted to constitute over 25% of the general population by 2050. In 2012 already 48% of the population with end stage renal disease (ESRD) was aged 65years or older. Transplantation is considered the preferred treatment option for ESRD offering survival advantage over long-term dialysis in the majority of patients. Indeed, acceptable outcomes have been documented for selected patients over the age of 70years or even cases over 80years. The reality of organ scarcity and prolonged waiting times for a deceased donor kidney transplantation, however, indicate that at best 50% of the selected elderly may have realistic expectations to receive a timely transplant offer. By choice or medical selection, access to transplantation also decreases with increasing age. In order to expedite the chance for elderly to receive a kidney transplant dedicated allocation systems have been developed. These allocation systems, like the Eurotransplant Senior Program (ESP), support preferential local allocation of kidneys from older donors to older patients in order to match recipient and graft life while disregarding histocompatibility for HLA antigens. The consequence has been more acute rejection episodes and an increase in immunosuppressive load. In the elderly, the most common cause of graft loss is death with functioning graft and death from infectious diseases is one of the dominant causes. The Eurotransplant Senior DR-compatible Program (ESDP) was designed to further improve the perspective of successful transplantation in the elderly in terms of life and quality of life by re-introducing matching criteria for HLA-DR in the old-for-old algorithm.