Cervical cancer prevention in Southern Africa: A review of national cervical cancer screening guidelines in the Southern African development community.

BACKGROUND: Cervical cancer poses a significant burden, particularly in low-and-middle income countries (LMIC) with limited access to healthcare. High-income countries have made progress in prevention, while LMIC face unacceptably high incidence and mortality rates, often lacking official screening recommendations. We analysed the presence and content of cervical cancer screening guidelines for the secondary prevention of cervical cancer in the Southern African Development Community (SADC) and compared it to the current World Health Organization (WHO) guidelines for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention. METHODS: A review of national cervical cancer guidelines across the SADC region was conducted. Data was obtained from government websites, international cancer control platforms, and WHO resources. Search terms included "cervical cancer" and "cervical cancer control guidelines", amongst others. There were no limitations on publication years, and the most recent versions of the guidelines were analysed, regardless of language. Each guideline was assessed for specific screening and treatment recommendations, in relation to the current WHO guidelines. Points were assigned for each data element. RESULTS: While most countries contributed data to this analysis there was a notable absence of adherence to the WHO guidelines. The most common screening method was naked eye visual inspection. There was a consensus on the age of screening initiation. Most countries recommended treatment by cryotherapy and loop excision. CONCLUSION: Effective cervical cancer screening programmes, guided by evidence-based recommendations, can enhance early intervention and outcomes. This study highlights the need for standardized and evidence-based cervical cancer screening guidelines in the SADC region, to reduce the burden of cervical cancer and improve the health outcomes of women in these areas.

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.

The response of geophytes to continuous human foraging on the Cape south coast, South Africa and its implications for early hunter-gatherer mobility patterns.

Current ecological understanding of plants with underground storage organs (USOs) suggests they have, in general, low rates of recruitment and thus as a resource it should be rapidly exhausted, which likely had implications for hunter-gatherer mobility patterns. We focus on the resilience (defined here as the ability of species to persist after being harvested) of USOs to human foraging. Human foragers harvested all visible USO material from 19 plots spread across six Cape south coast (South Africa) vegetation types for three consecutive years (2015-2017) during the period of peak USO apparency (September-October). We expected the plots to be depleted after the first year of harvesting since the entire storage organ of the USO is removed during foraging, i.e. immediate and substantial declines from the first to the second harvest. However, over 50% of the total weight harvested in 2015 was harvested in 2016 and 2017; only after two consecutive years of harvesting, was there evidence of significantly lower yield (p = 0.034) than the first (2015) harvest. Novel emergence of new species and new individuals in year two and three buffered the decline of harvested USOs. We use our findings to make predictions on hunter-gatherer mobility patterns in this region compared to the Hadza in East Africa and the Alyawara in North Australia.

Maternal and neonatal outcomes of COVID-19 in a high-risk pregnant cohort with and without HIV.

BACKGROUND: The impact of SARS-CoV-2 infection in pregnant women living with HIV (PLHIV) has not been described previously. OBJECTIVES: To describe the clinical presentation and outcomes of a cohort of women with high-risk pregnancies with confirmed COVID-19 to determine whether risk factors for disease severity and adverse outcomes of COVID-19 differed in pregnant women without HIV compared with PLHIV. METHODS: We prospectively enrolled pregnant women with COVID-19 attending the high-risk obstetric service at Tygerberg Hospital, Cape Town, South Africa, from 1 May to 31 July 2020, with follow-up until 31 October 2020. Women were considered high risk if they required specialist care for maternal, neonatal and/or anaesthetic conditions. Common maternal or obstetric conditions included hypertensive disorders, morbid obesity (body mass index (BMI) ≥40 kg/m2) and diabetes. Information on demographics, clinical features, and maternal and neonatal outcomes was collected and compared for PLHIV v. pregnant women without HIV. RESULTS: One hundred women (72 without HIV and 28 PLHIV) with high-risk pregnancies had laboratory-confirmed COVID-19. Among the 28 PLHIV, the median (interquartile range) CD4 count was 441 (317 - 603) cells/µL, and 19/26 (73%) were virologically suppressed. COVID-19 was diagnosed predominantly in the third trimester (81%). Obesity (BMI ≥30 in n=61/81; 75%) and hypertensive disorders were frequent comorbidities. Of the 100 women, 40% developed severe or critical COVID-19, 15% required intensive care unit admission and 6% needed invasive ventilation. Eight women died, 1 from advanced HIV disease complicated by bacteraemia and urosepsis. The crude maternal mortality rate was substantially higher in women with COVID-19 compared with all other deliveries at our institution during this period (8/91 (9%) v. 7/4 058 (0.2%); p<0.001). Neonatal outcomes were favourable. No significant differences in COVID-19 risk factors, disease severity, and maternal/neonatal outcome were noted for PLHIV v. those without HIV. CONCLUSIONS: In this cohort of high-risk pregnant women, the impact of COVID-19 was severe, significantly increasing maternal mortality risk compared with baseline rates. Virally suppressed HIV infection was not associated with worse COVID-19 outcomes in pregnancy.

Vulvar cancer is not a disease of the elderly: Treatment and outcome at a tertiary referral centre in South Africa.

BACKGROUND: An increase in vulvar cancer in young women is attributed to infection with oncogenic human papillomavirus (HPV). South Africa (SA) has a high prevalence of HPV, and it was therefore hypothesised that women with vulvar cancer here would be younger than in high-income countries (HICs). OBJECTIVE: To describe age, cancer stage, treatment and outcome of patients with vulvar cancer at a tertiary referral centre in SA. METHODS: In a retrospective observational study, patient records of women diagnosed with vulvar cancer between 2001 and 2014 were reviewed and demographic and surgical details captured. Histology results of vulvar biopsies and resected specimens were checked for HPV changes, koilocytes and usual-type vulval intraepithelial neoplasia. Patients were restaged using the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system to allow for comparison of outcomes. Five-year disease-specific survival probability curves were generated using Kaplan-Meier analysis. RESULTS: The mean age of the 180 patients in the study was 52.5 years. Those who had documented HPV changes on histological specimens had a mean age of 50.4 years. More than 50% of the patients had advanced-stage disease, and 62.7% were treated with primary surgery. Five-year disease-specific survival probabilities were similar to those reported in the literature. CONCLUSIONS: Vulvar cancer should not be regarded as a disease of the elderly in SA, as women with vulvar cancer are 10 - 15 years younger than in HICs. A large proportion of patients present with advanced-stage disease. Health professionals should be alert to vulvar lesions, especially in women with abnormal Pap smears, to reduce the morbidity and mortality of this disease.

In vitro inhibition of Plasmodium falciparum early and late stage gametocyte viability by extracts from eight traditionally used South African plant species.

ETHNOPHARMACOLOGICAL RELEVANCE: Extracts of plant species, used traditionally to treat malaria, have been extensively investigated for their activity against Plasmodium intraerythrocytic asexual parasites in search of new antimalarial drugs. However, less effort has been directed towards examining their efficacy in blocking transmission. Here, we report the results of the in vitro screening of extracts from eight selected plant species used traditionally to treat malaria in South Africa for activity against Plasmodium falciparum NF54 early and late stage gametocytes. The species used were Khaya anthotheca, Trichilia emetica, Turraea floribunda, Leonotis leonurus, Leonotis leonurus ex Hort, Olea europaea subsp. Africana, Catha edulis and Artemisia afra. AIM OF THE STUDY: To investigate the activities of extracts from plant species traditionally used for malaria treatment against P. falciparum gametocytes. MATERIAL AND METHODS: Air-dried and ground plant leaves were extracted using acetone. Primary two point in vitro phenotypic screens against both early and late stage gametocytes were done at 10 and 20µg/ml followed by full IC50 determination of the most active extracts. Inhibition of gametocyte viability in vitro was assessed using the parasite lactate dehydrogenase (pLDH) assay. RESULTS: Of the eight crude acetone extracts from plant species screened in vitro, four had good activity with over 50-70% inhibition of early and late stage gametocytes' viability at 10 and 20µg/ml, respectively. Artemisia afra (Asteraceae), Trichilia emetica (Meliaceae) and Turraea floribunda (Meliaceae) were additionally highly active against both gametocyte stages with IC50 values of less than 10µg/ml while Leonotis leonurus ex Hort (Lamiaceae) was moderately active (IC50<20µg/ml). The activity of these three highly active plant species was significantly more pronounced on late stage gametocytes compared to early stages. CONCLUSION: This study shows the potential transmission blocking activity of extracts from selected South African medicinal plants and substantiates their traditional use in malaria control that broadly encompasses prevention, treatment and transmission blocking. Further studies are needed to isolate and identify the active principles from the crude extracts of A. afra, T. emetica and T. floribunda, as well as to examine their efficacy towards blocking parasite transmission to mosquitoes.

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.