Ovarian cancer survival in sub-Saharan Africa by human development index and histological subtypes: A population-based registry study.

Ovarian cancer (OC) is the fourth most common cancer of women in sub-Saharan Africa (SSA), although few data have been published on population-level survival. We estimate ovarian cancer survival in SSA by human development index and histological subtype, using data from seven population-based cancer registries in six countries: Kenya (Nairobi and Eldoret), Mauritius, Uganda (Kampala), Cote d'Ivoire (Abidjan), Ethiopia (Addis Ababa) and South Africa (Eastern Cape). A total of 644 cases diagnosed during 2008-2014 were included, with 77% being of epithelial subtypes (range 47% [Abidjan]-80% [Mauritius]). The overall observed survival in the study cohort was 73.4% (95% CI: 69.8, 77.0) at 1 year, 54.4% (95% CI: 50.4, 58.7) at 3 years and 45.0% (95% CI: 41.0, 49.4) at 5 years. Relative survival at Year 1 ranged from 44.4% in Kampala to 86.3% in Mauritius, with a mean for the seven series of 67.4%. Relative survival was highest in Mauritius at 72.2% and lowest in Kampala, Uganda at 19.5%, with a mean of 47.8%. There was no difference in survival by age at diagnosis. Patients from high and medium HDI countries had significantly better survival than those from low HDI countries. Women with cancers of epithelial cell origin had much lower survival compared to women with other histological subtypes (p = .02). Adjusted for the young age of the African patients with ovarian cancer (44% aged <50) survival is much lower than in USA or Europe, and underlines the need for improvements in the access to diagnosis and treatment of OC in SSA.

Adherence to Treatment and Follow-Up of Precancerous Cervical Lesions in Ethiopia.

BACKGROUND: In Ethiopia, both incidence and mortality of cervical cancer are relatively high. Screening services, which were implemented during the past few years, are currently being expanded. The World Health Organization recommends patients with a positive VIA (visual inspection with acetic acid) result should immediately receive treatment followed by rescreening after 1 year as precancerous lesions can reoccur or become residential despite treatment. MATERIALS AND METHODS: Screening logbooks dating between 2017 and 2020 were retrospectively reviewed in 14 health facilities of Addis Ababa and Oromia region. Data for 741 women with a VIA-positive result were extracted and those women were asked to participate in a questionnaire-based phone interview to gain insights about adherence to treatment and follow-up. Data were analyzed using descriptive methods and then fitted into 2 generalized linear models to test variables for an influence on adherence to follow up. RESULTS: Around 13 800 women had received a VIA screening, of which approximately 820 (5.9%) were VIA positive. While over 90% of women with a positive screen received treatment, only about half of the treated patients returned for a follow-up examination. After treatment, 31 women had a VIA-positive re-screen. We found that educational status, age over 40, no/incorrect follow-up appointment, health facility-related barriers, and use of reminders are important drivers of adherence to follow up. CONCLUSION: Our results revealed that adherence to treatment after VIA positive screening is relatively high whereas adherence to follow up recommendations still needs improvement. Reminders like appointment cards and phone calls can effectively reduce the loss of follow-up.

Prognostic and predictive impact of NOTCH1 in early breast cancer.

PURPOSE: Systemic therapy plays a major part in the cure of patients with early breast cancer (eBC). However, personalized treatment concepts are required to avoid potentially harmful overtreatment. Biomarkers are pivotal for individualized therapy. The Notch signalling pathway is widely considered as a suitable prognostic or predictive marker in eBC. This study aimed primarily at assessing the relationship between NOTCH1 mRNA expression levels and histopathological features of breast cancer tumors, as well as clinical characteristics of the correspondent eBC patients. As a secondary aim, we investigated the prognostic and predictive value of NOTCH1 by assessing possible associations between NOTCH1 mRNA expression and recurrence-free interval (RFI) and overall survival after five years of observation. PATIENTS AND METHODS: The relative NOTCH1 mRNA expression was determined in 414 tumour samples, using quantitative PCR in a prospective, multicenter cohort (Prognostic Assessment in Routine Application (PiA), 2009-2011, NCT01592825) of 1,270 female eBC patients. RESULTS: High NOTCH1 mRNA expression was detected in one-third of the tumours and was associated with negative hormone receptor status and high uPA/PAI-1 status. In addition, high NOTCH1 mRNA expression was found to be associated with more RFI related events (adjusted hazard ratio 2.1, 95% CI 1.077-4.118). Patients who received adjuvant chemotherapy and had high NOTCH1 mRNA expression in the tumour (n = 86) were three times more likely to have an RFI event (adjusted hazard ratio 3.1, 95% CI 1.321-7.245, p = 0.009). CONCLUSION: In this cohort, NOTCH1 mRNA expression had a prognostic and predictive impact. Tumours with high NOTCH1 mRNA expression may be less sensitive to cytotoxic treatment and downregulation of the Notch signalling pathway (e.g. by γ-secretase inhibitors) may be valuable for eBC therapy as an individualised treatment option.

Understanding referral of patients with cancer in rural Ethiopia: a qualitative study.

BACKGROUND: Cancer incidence is increasing in Ethiopia mainly due to increased life expectancy, while oncological capacities remain limited. Strong referral linkages between different levels of the healthcare system are key to provide timely access to cancer care. In this qualitative study, we assessed limitations and potential of cancer patient referral in the rural Southwest of Ethiopia. METHODS: We held four focus group discussions (FGD) with health professionals at one primary and three secondary hospitals and conducted eight in-depth interviews (IDI) with the hospitals´ medical executives and local health bureau representatives. Data was analysed inductively using thematic analysis and emerging themes were categorized within the revised concept of access by Penchansky and Saurman. RESULTS: The inevitable referral of patients with cancer in the rural Southwest of Ethiopia is characterized by the absence of clear communication protocols and the lack of formal referral linkages. The newly implemented hub-system has improved emergency referrals and could be expanded to non-emergency referrals, sensitive to the needs of advanced oncological care. Liaison officers can pave the way but need to be trained and equipped adequately. Referred patients struggle with inadequate transportation systems, the lack of accommodation close to specialized facilities as well as the inability to navigate at those sites due to language barriers, illiteracy, and stigmatization. Few Non-Governmental Organizations (NGOs) help but cannot compensate the limited governmental support. The shortage of medications at public hospitals leads to patients being directed to costly private pharmacies. In the light of those challenges, cancer remains to be perceived as a "death sentence" within the rural communities. CONCLUSIONS: Standardized referral linkages and a multi-faceted support network throughout the cancer care continuum are necessary to make oncology care accessible to Ethiopia´s large rural population.

The effect of cognitive behavioural therapy integrated with activity pacing on cancer-related fatigue, depression and quality of life among patients with breast cancer undergoing chemotherapy in Ethiopia: A randomised clinical trial.

Fatigue is a common symptom experienced by 80% of individuals who receive chemotherapy and is one of the major factors that affect quality of life (QoL) of patients with breast cancer. Our study aimed to assess the effect of cognitive behavioural therapy integrated with activity pacing (CBT-AP) on cancer-related fatigue among patients with breast cancer undergoing chemotherapy. A parallel-group, randomised controlled trial was conducted. Severely fatigued patients were randomly assigned to the CBT-AP or usual care (UC) groups using a computer-generated random sequence. The new intervention was designed for seven sessions: three 2-hour face-to-face and four 30-minute telephone sessions. The primary outcome (fatigue severity) and the secondary outcomes (depression and QoL) were assessed at the end of the intervention and after 3 months. The data were analysed by repeated measures analyses of covariance (RM-ANCOVA). CBT-AP had a significant time effect (P < .001, ηp2  = 0.233) in reducing fatigue from baseline (adjusted mean = 7.48) to the end of the intervention (adjusted mean = 6.37) and the 3-month follow-up (adjusted mean = 6.54). Compared to the UC group, the CBT-AP group had lower fatigue and depression scores, and higher global health status scores. The group × time interaction revealed a significant reduction in fatigue and depression in the CBT-AP group compared to the UC group. Therefore, CBT-AP appears to be effective in reducing fatigue and depression and improving QoL in patients with breast cancer undergoing chemotherapy. It is highly recommended to integrate a CBT-AP intervention in routine cancer care.

Trends in the incidence of ovarian cancer in sub-Saharan Africa.

Ovarian cancer (OC) is one of the commonest cancers of women in sub-Saharan Africa (SSA), although to date no data have been available on time trends in incidence to better understand the disease pattern in the region. We estimate time trends by histological subtype from 12 population-based cancer registries in 11 countries: Kenya (Nairobi), Mauritius, Seychelles, Uganda (Kampala), Congo (Brazzaville), Zimbabwe (Bulawayo and Harare), Cote d'Ivoire (Abidjan), The Gambia, Mali (Bamako), Nigeria (Ibadan) and South Africa (Eastern Cape). The selected registries were those that could provide consistent estimates of the incidence of ovarian cancer and with quality assessment for periods of 10 or more years. A total of 5423 cases of OC were included. Incidence rates have been increasing in all registries except Brazzaville, Congo, where a nonsignificant decline of 1% per year was seen. Statistically significant average annual increases were seen in Mauritius (2.5%), Bamako (5.3%), Ibadan (3.9%) and Eastern Cape (8%). Epithelial ovarian cancer was responsible for the increases observed in all registries. Statistically significant average annual percentage changes (AAPC) for epithelial OC were present in Bamako (AAPC = 5.9%), Ibadan (AAPC = 4.7%) and Eastern Cape (AAPC = 11.0%). Creating awareness among professionals of the growing importance of the disease is surely an important step to improving availability of, and access to, diagnosis and treatment of OC in SSA. Support must be given to the cancer registries to improve the availability of good-quality data on this important cancer.

Pathways and Referral of Patients with Cancer in Rural Ethiopia: A Multi-center Retrospective Cohort Study.

INTRODUCTION: Well-organized patient pathways are essential to achieve early diagnosis and timely treatment of patients with cancer in Sub-Saharan Africa. This retrospective cohort study describes pathways and referral patterns of cancer patients in rural Ethiopia. PATIENTS AND METHODS: The retrospective study took place from October to December 2020 at 2 primary- and 6 secondary-level hospitals in southwestern Ethiopia. Of 681 eligible patients diagnosed with cancer between July 2017 and June 2020, 365 patients were included. Structured interviews on the patients' pathways were conducted by telephone. The primary outcome was successful referral, which was defined as occurring when the intended procedure was initiated at the receiving institution. Logistic regression was used to assess factors associated with successful referrals. RESULTS: Patients visited on average 3 health care institutions from their first encounter with a provider until their final treatment initiation. After diagnosis, only 26% (95) of patients were referred for further cancer treatment, of which 73% were successful. Patients referred for diagnostic tests were 10 times more likely to complete referrals successfully than patients referred for treatment. Overall, 21% of all patients remained without any therapy. CONCLUSION: We found that referral pathways of patients with cancer in rural Ethiopia were largely cohesive. The majority of patients referred for diagnostic or treatment services followed the advice. Nevertheless, an unacceptable number of patients remained without any treatment. Capacity for cancer diagnosis and treatment at primary- and secondary-level health facilities in rural Ethiopia must be expanded to enable early detection and timely care.

Guideline Concordance of Treatment and Outcomes Among Adult Non-Hodgkin Lymphoma Patients in Sub-Saharan Africa: A Multinational, Population-Based Cohort.

BACKGROUND: Although non-Hodgkin lymphoma (NHL) is the 6th most common malignancy in Sub-Saharan Africa (SSA), little is known about its management and outcome. Herein, we examined treatment patterns and survival among NHL patients. METHODS: We obtained a random sample of adult patients diagnosed between 2011 and 2015 from 11 population-based cancer registries in 10 SSA countries. Descriptive statistics for lymphoma-directed therapy (LDT) and degree of concordance with National Comprehensive Cancer Network (NCCN) guidelines were calculated, and survival rates were estimated. FINDINGS: Of 516 patients included in the study, sub-classification was available for 42.1% (121 high-grade and 64 low-grade B-cell lymphoma, 15 T-cell lymphoma and 17 otherwise sub-classified NHL), whilst the remaining 57.9% were unclassified. Any LDT was identified for 195 of all patients (37.8%). NCCN guideline-recommended treatment was initiated in 21 patients. This corresponds to 4.1% of all 516 patients, and to 11.7% of 180 patients with sub-classified B-cell lymphoma and NCCN guidelines available. Deviations from guideline-recommended treatment were initiated in another 49 (9.5% of 516, 27.2% of 180). By registry, the proportion of all patients receiving guideline-concordant LDT ranged from 30.8% in Namibia to 0% in Maputo and Bamako. Concordance with treatment recommendations was not assessable in 75.1% of patients (records not traced (43.2%), traced but no sub-classification identified (27.8%), traced but no guidelines available (4.1%)). By registry, diagnostic work-up was in part importantly limited, thus impeding guideline evaluation significantly. Overall 1-year survival was 61.2% (95%CI 55.3%-67.1%). Poor ECOG performance status, advanced stage, less than 5 cycles and absence of chemo (immuno-) therapy were associated with unfavorable survival, while HIV status, age, and gender did not impact survival. In diffuse large B-cell lymphoma, initiation of guideline-concordant treatment was associated with favorable survival. INTERPRETATION: This study shows that a majority of NHL patients in SSA are untreated or undertreated, resulting in unfavorable survival. Investments in enhanced diagnostic services, provision of chemo(immuno-)therapy and supportive care will likely improve outcomes in the region.

[Climate Crisis: What Gastrointestinal Complications of this Medical Emergency Should We Be Aware Of?] / Klimakrise: Welche gastroenterologischen Folgeerkrankungen dieses medizinischen Notfalls sollten wir kennen?

INTRODUCTION: The climate crisis has serious consequences for many areas of life. This applies in particular to human health - also in Europe. While cardiovascular, pneumological and dermatological diseases related to the climate crisis are often discussed, the crisis' significant gastroenterological consequences for health must also be considered. METHODS: A literature search (Pubmed, Cochrane Library) was used to identify papers with relevance particularly to the field of gastroenterology in (Central) Europe. Findings were supplemented and discussed by an interdisciplinary team. RESULTS: The climate crisis impacts the frequency and severity of gastrointestinal diseases in Europe due to more frequent and severe heat waves, flooding and air pollution. While patients with intestinal diseases are particularly vulnerable to acute weather events, the main long-term consequences of climate change are gastrointestinal cancer and liver disease. In addition to gastroenteritis, other infectious diseases such as vector-borne diseases and parasites are important in the context of global warming, heat waves and floods. DISCUSSION: Adaptation strategies must be consistently developed and implemented for vulnerable groups. Patients at risk should be informed about measures that can be implemented individually, such as avoiding heat, ensuring appropriate hydration and following hygiene instructions. Recommendations for physical activity and a healthy and sustainable diet are essential for the prevention of liver diseases and carcinomas. Measures for prevention and the promotion of resilience can be supported by the physicians at various levels. In addition to efforts fostering sustainability in the immediate working environment, a system-oriented commitment to climate protection is important.

Intrinsic subtypes in Ethiopian breast cancer patient.

PURPOSE: The recent development of multi-gene assays for gene expression profiling has contributed significantly to the understanding of the clinically and biologically heterogeneous breast cancer (BC) disease. PAM50 is one of these assays used to stratify BC patients and individualize treatment. The present study was conducted to characterize PAM50-based intrinsic subtypes among Ethiopian BC patients. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tissues were collected from 334 BC patients who attended five different Ethiopian health facilities. All samples were assessed using the PAM50 algorithm for intrinsic subtyping. RESULTS: The tumor samples were classified into PAM50 intrinsic subtypes as follows: 104 samples (31.1%) were luminal A, 91 samples (27.2%) were luminal B, 62 samples (18.6%) were HER2-enriched and 77 samples (23.1%) were basal-like. The intrinsic subtypes were found to be associated with clinical and histopathological parameters such as steroid hormone receptor status, HER2 status, Ki-67 proliferation index and tumor differentiation, but not with age, tumor size or histological type. An immunohistochemistry-based classification of tumors (IHC groups) was found to correlate with intrinsic subtypes. CONCLUSION: The distribution of the intrinsic subtypes confirms previous immunohistochemistry-based studies from Ethiopia showing potentially endocrine-sensitive tumors in more than half of the patients. Health workers in primary or secondary level health care facilities can be trained to offer endocrine therapy to improve breast cancer care. Additionally, the findings indicate that PAM50-based classification offers a robust method for the molecular classification of tumors in the Ethiopian context.

PIK3CA-mutations in breast cancer.

PURPOSE: Phosphatidylinositide-3-kinase (PI3K) regulates proliferation and apoptosis; somatic PIK3CA-mutations may activate these processes. Aim of this study was to determine the prevalence of PIK3CA-mutations in a cohort of early stage breast cancer patients and the association to the course of disease. PATIENTS AND METHODS: From an unselected cohort of 1270 breast cancer patients (PiA, Prognostic Assessment in routine application, NCT01592825) 1123 tumours were tested for the three PIK3CA hotspot-mutations H1047R, E545K, and E542K by qPCR. Primary objectives were the prevalence of somatic PIK3CA-mutations and their association to tumour characteristics. Secondary objective was the association of PIK3CA-mutations to recurrence-free interval (RFI) and overall survival. RESULTS: PIK3CA-mutation rate was 26.7% (300 of 1123). PIK3CA-mutations were significantly more frequent in steroid hormone-receptor (SHR)-positive HER2-negative (31.4%), and G1 and G2 tumours (32.8%). Overall, we did not observe a significant association of PIK3CA-mutations to RFI. In SHR-positive BCs with PIK3CA-mutations, a strong trend for impaired  RFI was observed (adjusted HR 1.64, 95% CI 0.958-2.807), whilst in SHR-negative BCs PIK3CA-mutations were insignificantly associated with improved RFI (adjusted HR 0.49; 95% CI 0.152-1.597). Of note, we observed a significantly detrimental prognostic impact of PIK3CA-mutations on RFI in SHR-positive, HER2-negative BCs if only aromatase inhibitors were administered as adjuvant therapy (adjusted HR 4.44, 95% CI 1.385-13.920), whilst no impact was observed in tamoxifen treated patients. CONCLUSION: This cohort study speficies the overall mutation rate of PIK3CA in early breast cancer. The impact of PIK3CA-mutations on RFI and OS was heterogeneous. Our results suggest that estrogen deprivation failes to be active in case of PIK3CA-mutation.

Quality of life and its influencing factors among breast cancer patients at Tikur Anbessa specialised hospital, Addis Ababa, Ethiopia.

BACKGROUND: Quality of life (QoL) has become an important measure for evaluating cancer patients' treatment and prognosis. Breast cancer patients are at an increased risk of experiencing poor QoL during active treatment of cancer. This study aimed to assess QoL and it's influencing factors among breast cancer patients using the newly updated breast cancer specific tool of the European Organisation for Research and Treatment of Cancer EORTC Breast Cancer Specific Quality of Life Questionnaire QLQ-BR45. METHODS: An institutional based crossectional study was conducted with 248 breast cancer patients at Tikur Anbessa Specialized Hospital (TASH). Descriptive statistics, one-way analysis of variance (ANOVA), and linear regression were used to describe and analyze the data. RESULTS: The participant's Global health status/QoL mean score was 65.6. Among the functional scales, future perspective scored the lowest (57.1, SD ± 37.3). The highest mean score on the symptom scales/items were financial difficulties (50, SD ± 38.6), followed by appetite loss (37.4, SD ± 36.4) and fatigue (34.3, SD ± 27.1) while the lowest symptom score was diarrhoea (6.4 ± 18.4). EORTC QLQ-BR45, future perspective (mean = 57.1, SD ± 37.3) and upset by hair loss (41.8, SD ± 34.6) were the most affected functioning and symptoms scales respectively. An increased stage of tumor was associated with more pain (P = 0.041), appetite loss (P = 0.042), and arm symptoms (P = 0.003). Patients who had no comorbidity had better physical (P < 0.001), cognitive (P = 0.013), and social (P = 0.009) function. CONCLUSION: These specific functional scales and symptoms should be assessed individually to address unmet needs. Clinicians could design psychosocial interventions to improve these function and to reduce symptoms.

Women's sexual autonomy as a determinant of cervical cancer screening uptake in Addis Ababa, Ethiopia: a case-control study.

Cervical cancer (CC) is the fourth most common cancer in women worldwide and the leading cause of cancer deaths in developing countries. CC can be prevented through available preventive interventions. However, most patients in developing countries, such as Ethiopia, present late with advanced stage disease due to low participation in CC screening and require treatment involving multiple modalities. Women's social, economic and cultural backgrounds have been associated with the level of participation in CC screening programmes. Therefore, this study aimed to assess women's sexual autonomy as a determinant of lifetime CC screening among women in Addis Ababa, Ethiopia. An institutional-based case-control study was conducted in which controls were women who had received screening services during the last 5 years, and cases were randomly selected from women coming for other services but never screened or aware of the screening service. Accordingly, 294 women were enrolled. Data were collected by using a pre-tested standard questionnaire through interviewing. Bivariate and multivariable logistic regression analyses were performed to assess the women's sexual autonomy as a determinant of lifetime CC screening. The study revealed higher sexual autonomy led to higher odds for having been screened (adjusted odds ratio (AOR) = 3.128, 95% CI (1.730, 5.658)). Moreover, direct referral to the screening service (AOR = 3.173, 95% CI (1.57, 6.45)) and parity had positively affected the lifetime uptake of CC screening (AOR = 2.844, 95% CI (1.344, 6.014)). We found that women's own sexual autonomy was associated with the improvement of CC screening uptake. Empowering women could alleviate barriers to CC screening in the community.

Predictors of unmet supportive care needs of adult cancer patients in Ethiopia.

OBJECTIVE: Cancer is a global public health issue that continues to increase because of aging and adoption of cancer-causing behaviours. In Ethiopia, cancer belongs to the second most common non-communicable disease. Cancer patients face a range of unmet needs in multiple aspects of their lives. Supportive care is defined as essential care that helps patients to cope with cancer. This study aims to assess the predictors of unmet supportive care needs in adult cancer patients in Ethiopia. METHODS: Institution-based cross-sectional study was done from February to March 2019 in adult cancer patients. Three hundred seventy-one patients were interviewed using convenience sampling. Supportive care needs were used as outcome variables, dichotomized as 'no need' and 'unmet needs'. Variables with a p-value of <0.2 were candidates for multivariable logistic regression. RESULTS: From 371 patients, 69.8% were females with a mean age of 47 years; the commonest type of cancer was gynaecological cancer. Information about diagnosis, stage of cancer, time since diagnosis, age, wealth index, employment status, gender, type of treatment, history of recurrence, type of cancer and information about diagnosis modified by the source of information were predictors of unmet supportive care needs. CONCLUSIONS: The study emphasised the importance of considering sociodemographic, clinical and information-related factors when dealing with cancer patients. Programmes, guidelines and services that focus on supportive care needs should be established and/or implemented.

Association between waiting time for radiotherapy initiation and disease progression among women with cervical cancer in Addis Ababa, Ethiopia.

There is shortage of radiotherapy machines in low-income countries, including Ethiopia. Data on adverse effects of this on cancer outcomes are limited, however. Herein, we examined the extent of waiting time for radiotherapy and its association with disease progression based on a prospective cohort study of women diagnosed with stage IA-IVA cervical cancer in Addis Ababa and who were scheduled to receive radiotherapy at Tikur Anbessa Specialized Hospital, the only hospital that provides radiotherapy services in the country. Association was examined using Multivariable mixed effects logistic regression model. Among the 178 women with cervical cancer scheduled for receipt of radiotherapy and with vital status information, 16 deceased (9.0%) while waiting for radiotherapy. For the remaining 162 women who initiated radiotherapy, the median treatment waiting period was 137 days (IQR = 60-234 days), with 74.1% of women waiting for >60 days. Tumor progressed to higher stage for 44.4% of these women. Compared to those women who initiated radiotherapy ≤60 days after diagnostic confirmation, the odds of tumor progression to higher stage was three times higher in those women who initiated radiotherapy between 120-179 days (aOR =3.30, 95%CI: 1.18-9.27) and ≥180 days (aOR =3.06, 95%CI: 1.24-7.52). Waiting period for receipt of radiotherapy among women with cervical cancer is exceedingly long in Addis Ababa, and it is associated with disease progression to higher stages. These findings reinforce the need to expand radiotherapy infrastructure in order to mitigate the undue high burden of the disease in Ethiopia and other parts of Africa.

Trends in childhood cancer incidence in sub-Saharan Africa: Results from 25 years of cancer registration in Harare (Zimbabwe) and Kyadondo (Uganda).

We examined trends in childhood cancer incidence in sub-Saharan Africa using data from two population-based cancer registries in Harare (Zimbabwe) and Kyadondo (Uganda) with cases classified according to the International Classification of Childhood Cancer and explored reasons for observed variations and changes. Over the whole 25-year period (1991-2015) studied, there were only small, and nonsignificant overall trends in incidence. Nevertheless, within the period, peaks in incidence occurred from 1996 to 2001 in Harare (Zimbabwe) and from 2003 to 2006 in Kyadondo (Uganda). Kaposi sarcoma and non-Hodgkin lymphoma accounted for the majority of the cases during these periods. These fluctuations in incidence rates in both registries can be linked to similar trends in the prevalence of HIV, and the availability of antiretroviral therapy. In addition, we noted that, in Harare, incidence rates dropped from 2003 to 2004 and 2007 to 2008, correlating with declines in national gross domestic product. The results indicate that the registration of childhood cancer cases in resource-poor settings is linked to the availability of diagnostic services mediated by economic developments. The findings highlight the need for specialised diagnostic and treatment programmes for childhood cancer patients as well as positive effects of HIV programmes on certain childhood cancers.

Population-based human papillomavirus infection and genotype distribution among women in rural areas of South Central Ethiopia.

In Ethiopia, cervical cancer is the second leading cause of morbidity and mortality from all cancers in women. Persistent infection with human papillomaviruses (HPV) plays a key role in the development of cervical intraepithelial neoplasia and invasive cervical cancer. To establish baseline data on the population-based prevalence of HPV infection and genotype distribution, we investigated cervical HPV epidemiology among rural women. This population-based study was conducted among rural women aged 30-49 years in Butajira, south-central Ethiopia. A total of 893 samples were tested from 1020 screened women. A self-sampling device (Evalyn Brush, Rovers, Oss, The Netherlands) was used and HPV presence and genotype was determined using multiplexed genotyping (MPG) by BSGP5+/6+ PCR with Luminex read out. The HPV positivity rate was 23.2% (95% CI: 23.54-22.86%) and 20.5% (95% CI = 20.79-20.21) and 10.3% (95% CI = 10.52-10.08) women were high-risk (hr- and low-risk (lr-) HPV positive, respectively. Fifty five (7.2%) of the women showed multiple hr-HPV infections. Age-specific hr-HPV infection peaked in the age-group 30- to 34 years old (58.6%) and decreased in 35-39, 40-44 and 45-49 years to 20.4%, 4.5% and 3.8% respectively. The top five prevalent hr-HPV genotypes were HPV16 (57.1%), 35 (20.3%), 52 (15.8%), 31 (14.1%), and 45 (9.6%) in the Butajira district. As a first population-based study in the country, our results can serve as valuable reference to guide nationwide cervical cancer screening and HPV vaccination programs in Ethiopia.

Abrogating GPT2 in triple-negative breast cancer inhibits tumor growth and promotes autophagy.

Uncontrolled proliferation and altered metabolic reprogramming are hallmarks of cancer. Active glycolysis and glutaminolysis are characteristic features of these hallmarks and required for tumorigenesis. A fine balance between cancer metabolism and autophagy is a prerequisite of homeostasis within cancer cells. Here we show that glutamate pyruvate transaminase 2 (GPT2), which serves as a pivot between glycolysis and glutaminolysis, is highly upregulated in aggressive breast cancers, particularly the triple-negative breast cancer subtype. Abrogation of this enzyme results in decreased tricarboxylic acid cycle intermediates, which promotes the rewiring of glucose carbon atoms and alterations in nutrient levels. Concordantly, loss of GPT2 results in an impairment of mechanistic target of rapamycin complex 1 activity as well as the induction of autophagy. Furthermore, in vivo xenograft studies have shown that autophagy induction correlates with decreased tumor growth and that markers of induced autophagy correlate with low GPT2 levels in patient samples. Taken together, these findings indicate that cancer cells have a close network between metabolic and nutrient sensing pathways necessary to sustain tumorigenesis and that aminotransferase reactions play an important role in maintaining this balance.

Presentation, patterns of care, and outcomes of patients with prostate cancer in sub-Saharan Africa: A population-based registry study.

BACKGROUND: Although prostate cancer (PCa) is the most commonly diagnosed cancer in men of sub-Saharan Africa (SSA), little is known about its management and survival. The objective of the current study was to describe the presentation, patterns of diagnosis, treatment, and survival of patients with PCa in 10 countries of SSA. METHODS: In this observational registry study with data collection from 2010 to 2018, the authors drew a random sample of 738 patients with PCa who were registered in 11 population-based cancer registries. They described proportions of patients receiving recommended care and presented survival estimates. Multivariable Cox regression was used to calculate hazard ratios comparing the survival of patients with and without cancer-directed therapies (CDTs). RESULTS: The study included 693 patients, and tumor characteristics and treatment information were available for 365 patients, 37.3% of whom had metastatic disease. Only 11.2% had a complete diagnostic workup for risk stratification. Among the nonmetastatic patients, 17.5% received curative-intent therapy, and 27.5% received no CDT. Among the metastatic patients, 59.6% received androgen deprivation therapy. The 3- and 5-year age-standardized relative survival for 491 patients with survival time information was 58.8% (95% confidence interval [CI], 48.5%-67.7%) and 56.9% (95% CI, 39.8%-70.9%), respectively. In a multivariable analysis, survival was considerably poorer among patients without CDT versus those with therapy. CONCLUSIONS: This study shows that a large proportion of patients with PCa in SSA are not staged or are insufficiently staged and undertreated, and this results in unfavorable survival. These findings reemphasize the need for improving diagnostic workup and access to care in SSA in order to mitigate the heavy burden of the disease in the region.

Factors associated with late-stage diagnosis of breast cancer among women in Addis Ababa, Ethiopia.

PURPOSE: Stage at diagnosis is a key determinant of breast cancer prognosis. In this study, we characterize stage at diagnosis and determine factors associated with advanced stage at diagnosis among women diagnosed with invasive breast cancer in Addis Ababa, capital city of Ethiopia. METHODS: Stage information was collected from medical records of 441 women with invasive breast cancer seen in seven major health facilities in Addis Ababa, from January 2017 to June 2018; these seven facilities capture 90% of all incident breast cancer cases in the city. We used multivariable Poisson regression model with robust variance to determine factors associated with advanced stage at diagnosis. RESULTS: The predominant tumor histology was ductal carcinoma (83.7%). More than half of the tumors' grade was moderately or poorly differentiated. The median tumor size at presentation was 4 cm. Sixty-four percent of the patients were diagnosed at advanced stage of the disease (44% stage III and 20% stage IV), with 36% of the patients diagnosed at early-stage (5% stage I and 31% stage II). The prevalence of advanced stage disease was significantly higher among women who used traditional medicine before diagnostic confirmation (adjusted prevalence ratio [aPR] = 1.31; p = 0.001), had patient delay of >  3 months (aPR = 1.16; p = 0.042) and diagnosis delay of > 2 months (aPR = 1.24; p = 0.004). But it was lower among women who had history of breast self-examination (aPR = 0.77; p = 0.021). CONCLUSIONS: Advanced stage at diagnosis of breast cancer among women in Addis Ababa is strongly associated with use of traditional medicine and with prolonged time interval between symptom recognition and disease confirmation. Community- and health systems-level interventions are needed to enhance knowledge about breast cancer and facilitate timely diagnoses.