Trends in the incidence of colorectal cancer in sub-Saharan Africa: A population-based registry study.

In sub-Saharan Africa, colorectal cancer (CRC) has historically been considered a rare disease, although some previous studies have suggested that the incidence is increasing. We examine time trends in the incidence of CRC using data from 12 population-based cancer registries in 11 countries of sub-Saharan Africa that were able to provide time series data for periods of 12 or more years, or with earlier data with which recent rates may be compared. Age-standardized incidence rates were highest in the higher-income countries, and were increasing in all of the populations studied, and these increases were statistically significant in all but three. Current evidence has suggested a link between the increased adoption of western lifestyle habits with colorectal cancer, and along with increasing urbanization of African populations, there is an increase in body weight, as well as evidence of increasing consumption of meat, sugars, and alcohol.

Differential etiopathogenic features of vulvar squamous cell carcinomas in sub-Saharan Africa and Europe.

Two pathways have been described for vulvar squamous cell carcinomas (VSCC), one associated with human papillomavirus (HPV), and the other HPV-independent. We compared the etiopathogenic features of a series of VSCC from Mozambique, a sub-Saharan country with high prevalence of HPV and HIV, with those of Spain, a European country with low prevalence of HPV and HIV. All VSCC diagnosed at the two institutions from January 2018 to December 2020 were included (n = 35 and n = 41, respectively). HPV DNA detection and genotyping, and immunohistochemistry for p16 and p53 were performed. Tumors showing p16 positive staining and/or HPV DNA positivity were considered HPV-associated. 34/35 tumors (97%) from Mozambique and 8/41 (19%) from Spain were HPV-associated (P < .001). Mean age of the patients from Mozambique and Spain was 45 ± 12 and 72 ± 14, respectively (P < .001). No differences were found in terms of HPV genotypes or multiple HPV infection rates. 1/35 tumors (3%) from Mozambique and 29/41 (70%) from Spain showed abnormal p53 immunostaining (P < .001). In contrast with the predominance of HPV-independent VSCC affecting old women in Europe, most VSCC in sub-Saharan Africa are HPV-associated and arise in young women. This data may have important consequences for primary prevention of VSCC worldwide.

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.

The Mulher Study: cervical cancer screening with primary HPV testing in Mozambique.

OBJECTIVE: To evaluate cervical cancer screening with primary human papillomavirus (HPV) testing in Mozambique, a country with one of the highest burdens of cervical cancer globally. METHODS: Women aged 30-49 years were prospectively enrolled and offered primary HPV testing using either self-collected or provider-collected specimens. Patients who tested positive for HPV underwent visual assessment for treatment using visual inspection with acetic acid to determine eligibility for thermal ablation. If ineligible, they were referred for excision with a loop electrosurgical excision procedure, for cold knife conization, or for cervical biopsy if malignancy was suspected. RESULTS: Between January 2020 and January 2023, 9014 patients underwent cervical cancer screening. Median age was 37 years (range 30-49) and 4122 women (45.7%) were patients living with HIV. Most (n=8792, 97.5%) chose self-collection. The HPV positivity rate was 31.1% overall and 39.5% among patients living with HIV. Of the 2805 HPV-positive patients, 2588 (92.3%) returned for all steps of their diagnostic work-up and treatment, including ablation (n=2383, 92.1%), loop electrosurgical excision procedure (n=169, 6.5%), and cold knife conization (n=5, 0.2%). Thirty-one patients (1.2%) were diagnosed with cancer and referred to gynecologic oncology. CONCLUSION: It is feasible to perform cervical cancer screening with primary HPV testing and follow-up in low-resource settings. Participants preferred self-collection, and the majority of screen-positive patients completed all steps of their diagnostic work-up and treatment. Our findings provide important information for further implementation and scale-up of cervical cancer screening and treatment services as part of the WHO global strategy for the elimination of cervical cancer.

Clinical and epidemiological aspects of SARS-CoV-2 infection among pregnant and postpartum women in Mozambique: a prospective cohort study.

BACKGROUND: Although there is a significant increase of evidence regarding the prevalence and impact of COVID-19 on maternal and perinatal outcomes, data on the effects of the pandemic on the obstetric population in sub-Saharan African countries are still scarce. Therefore, the study aims were to assess the prevalence and impact of COVID-19 on maternal and neonatal outcomes in the obstetric population at Central Hospital of Maputo (HCM), Mozambique. METHODS: Prospective cohort study conducted at teaching and referral maternity, HCM, from 20 October 2020 to 22 July 2021. We collected maternal and perinatal outcomes up to 6 weeks postpartum of eligible women (pregnant and postpartum women-up to the 14th day postpartum) screened for COVID-19 (individual test for symptomatic participants and pool testing for asymptomatic). The primary outcome was maternal death, Severe Acute Respiratory Syndrome (SARS) and Intensive Care Unit (ICU) admission. We estimated the COVID-19 prevalence and the unadjusted RR (95% CI) for maternal and perinatal outcomes. We used the chi-square or Fisher's exact test to compare categorical variables (two-sided p-value < 0.05 for statistical significance). RESULTS: We included 239 participants. The overall prevalence of COVID-19 was 9.2% (22/239) and in the symptomatic group was 32.4% (11/34). About 50% of the participants with COVID-19 were symptomatic. Moreover, the most frequent symptoms were dyspnoea (33.3%), cough (28.6%), anosmia (23.8%), and fever (19%). Not having a partner, being pregnant, and alcohol consumption were vulnerability factors for SARS-CoV-2 infection. The risk of adverse maternal and neonatal outcomes (abortion, foetal death, preterm birth, Apgar, and NICU admission) was not significantly increased with COVID-19. Moreover, we did not observe a significant difference in the primary outcomes (SARS, ICU admission and maternal death) between COVID-19 positive and COVID-19 negative groups. CONCLUSION: The prevalence of COVID-19 in the obstetric population is higher than in the general population, and fifty percent of pregnant and postpartum women with COVID-19 infection are asymptomatic. Not having a partner and alcohol consumption were factors of greatest vulnerability to SARS-COV-2 infection. Moreover, being pregnant versus postpartum was associated with increased vulnerability to COVID-19. Data suggest that pregnant women with COVID-19 may have a higher frequency of  COVID-19 infection, reinforcing the need for universal testing, adequate follow-up for this population, and increasing COVID-19 therapy facilities in Mozambique. Moreover, provide counselling during Antenatal care for COVID-19 preventive measures. However, more prospective and robust studies are needed to assess these findings.

Minimally Invasive Tissue Sampling: A Tool to Guide Efforts to Reduce AIDS-Related Mortality in Resource-Limited Settings.

BACKGROUND: Available information on the causes of death among people living with human immunodeficiency virus (PLHIV) in low- and middle-income countries (LMICs) remains scarce. We aimed to provide data on causes of death in PLHIV from two LMICs, Brazil and Mozambique, to assess the impact of clinical misdiagnosis on mortality rates and to evaluate the accuracy of minimally invasive tissue sampling (MITS) in determining the cause of death in PLHIV. METHODS: We performed coupled MITS and complete autopsy on 164 deceased PLHIV (18 children, 36 maternal deaths, and 110 adults). HIV antibody levels and HIV RNA viral loads were determined from postmortem serum samples. RESULTS: Tuberculosis (22.7%), toxoplasmosis (13.9%), bacterial infections (13.9%), and cryptococcosis (10.9%) were the leading causes of death in adults. In maternal deaths, tuberculosis (13.9%), bacterial infections (13.9%), cryptococcosis (11.1%), and cerebral malaria (8.3%) were the most frequent infections, whereas viral infections, particularly cytomegalovirus (38.9%), bacterial infections (27.8%), pneumocystosis (11.1%), and HIV-associated malignant neoplasms (11.1%) were the leading cause among children. Agreement between the MITS and the complete autopsy was 100% in children, 91% in adults, and 78% in maternal deaths. The MITS correctly identified the microorganism causing death in 89% of cases. CONCLUSIONS: Postmortem studies provide highly granular data on the causes of death in PLHIV. The inaccuracy of clinical diagnosis may play a significant role in the high mortality rates observed among PLHIV in LMICs. MITS might be helpful in monitoring the causes of death in PLHIV and in highlighting the gaps in the management of the infections.

Colorectal cancer survival in sub-Saharan Africa by age, stage at diagnosis and Human Development Index: A population-based registry study.

There are limited population-based survival data for colorectal cancer (CRC) in sub-Saharan Africa. Here, 1707 persons diagnosed with CRC from 2005 to 2015 were randomly selected from 13 population-based cancer registries operating in 11 countries in sub-Saharan Africa. Vital status was ascertained from medical charts or through next of kin. 1-, 3- and 5-year overall and relative survival rates for all registries and for each registry were calculated using the Kaplan-Meier estimator. Multivariable analysis was used to examine the associations of 5-year relative survival with age at diagnosis, stage and country-level Human Development Index (HDI). Observed survival for 1448 patients with CRC across all registries combined was 72.0% (95% CI 69.5-74.4%) at 1 year, 50.4% (95% CI 47.6-53.2%) at 3 years and 43.5% (95% CI 40.6-46.3%) at 5 years. We estimate that relative survival at 5 years in these registry populations is 48.2%. Factors associated with poorer survival included living in a country with lower HDI, late stage at diagnosis and younger or older age at diagnosis (<50 or ≥70 years). For example, the risk of death was 1.6 (95% CI 1.2-2.1) times higher for patients residing in medium-HDI and 2.7 (95% CI 2.2-3.4) times higher for patients residing in low-HDI compared to those residing in high-HDI countries. Survival for CRC remains low in sub-Saharan African countries, though estimates vary considerably by HDI. Strengthening health systems to ensure access to prevention, early diagnosis and appropriate treatment is critical in improving outcomes of CRC in the region.

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.

Survival Impact and Cost-Effectiveness of a Multidisciplinary Tumor Board for Breast Cancer in Mozambique, Sub-Saharan Africa.

BACKGROUND: Despite the international endorsement of multidisciplinary tumor boards (MTBs) for breast cancer care, implementation is suboptimal worldwide, and evidence regarding their effectiveness in developing countries is lacking. We assessed the impact on survival and the cost-effectiveness of implementing an MTB in Mozambique, sub-Saharan Africa. MATERIALS AND METHODS: This prospective cohort study included 205 patients with breast cancer diagnosed between January 2015 and August 2017 (98 before and 107 after MTB implementation), followed to November 2019. Pre- and post-MTB implementation subcohorts were compared for clinical characteristics, treatments, and overall survival. We used hazard ratios and 95% confidence intervals (CI), computed by Cox proportional hazards regression. The impact of MTB implementation on the cost per quality-adjusted life year (QALY) was estimated from the provider perspective. RESULTS: We found no significant differences between pre- and post-MTB subcohorts regarding clinical characteristics or treatments received. Among patients with early breast cancer (stage 0-III; n = 163), the 3-year overall survival was 48.0% (95% CI, 35.9-59.1) in the pre-MTB and 73.0% (95% CI, 61.3-81.6) in the post-MTB subcohort; adjusted hazard ratio, 0.47 (95% CI, 0.27-0.81). The absolute 3-year mean cost increase was $119.83 per patient, and the incremental cost-effectiveness ratio was $802.96 per QALY, corresponding to 1.6 times the gross domestic product of Mozambique. CONCLUSION: The implementation of a MTB in Mozambique led to a 53% mortality decrease among patients with early breast cancer, and it was cost-effective. These findings highlight the feasibility of implementing this strategy and the need for scaling-up MTBs in developing countries, as a way to improve patient outcomes. IMPLICATIONS FOR PRACTICE: Currently, more than half of the deaths from breast cancer in the world occur in developing countries. Strategies that optimize care and that are adjusted for available resources are needed to improve the outcomes of patients with breast cancer in these regions. The discussion of cases at multidisciplinary tumor boards (MTBs) may improve survival outcomes, but implementation is suboptimal worldwide, and evidence regarding their effectiveness in developing countries is lacking. This study evaluated the impact of implementing an MTB on the care and survival of patients with breast cancer in Mozambique, sub-Saharan Africa and its cost-effectiveness in this low-income setting.

Cervical Cancer in Sub-Saharan Africa: A Multinational Population-Based Cohort Study of Care and Guideline Adherence.

BACKGROUND: Cervical cancer (CC) is the most common female cancer in many countries of sub-Saharan Africa (SSA). We assessed treatment guideline adherence and its association with overall survival (OS). METHODS: Our observational study covered nine population-based cancer registries in eight countries: Benin, Ethiopia, Ivory Coast, Kenya, Mali, Mozambique, Uganda, and Zimbabwe. Random samples of 44-125 patients diagnosed from 2010 to 2016 were selected in each. Cancer-directed therapy (CDT) was evaluated for degree of adherence to National Comprehensive Cancer Network (U.S.) Guidelines. RESULTS: Of 632 patients, 15.8% received CDT with curative potential: 5.2% guideline-adherent, 2.4% with minor deviations, and 8.2% with major deviations. CDT was not documented or was without curative potential in 22%; 15.7% were diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IV disease. Adherence was not assessed in 46.9% (no stage or follow-up documented, 11.9%, or records not traced, 35.1%). The largest share of guideline-adherent CDT was observed in Nairobi (49%) and the smallest in Maputo (4%). In patients with FIGO stage I-III disease (n = 190), minor and major guideline deviations were associated with impaired OS (hazard rate ratio [HRR], 1.73; 95% confidence interval [CI], 0.36-8.37; HRR, 1.97; CI, 0.59-6.56, respectively). CDT without curative potential (HRR, 3.88; CI, 1.19-12.71) and no CDT (HRR, 9.43; CI, 3.03-29.33) showed substantially worse survival. CONCLUSION: We found that only one in six patients with cervical cancer in SSA received CDT with curative potential. At least one-fifth and possibly up to two-thirds of women never accessed CDT, despite curable disease, resulting in impaired OS. Investments into more radiotherapy, chemotherapy, and surgical training could change the fatal outcomes of many patients. IMPLICATIONS FOR PRACTICE: Despite evidence-based interventions including guideline-adherent treatment for cervical cancer (CC), there is huge disparity in survival across the globe. This comprehensive multinational population-based registry study aimed to assess the status quo of presentation, treatment guideline adherence, and survival in eight countries. Patients across sub-Saharan Africa present in late stages, and treatment guideline adherence is remarkably low. Both factors were associated with unfavorable survival. This report warns about the inability of most women with cervical cancer in sub-Saharan Africa to access timely and high-quality diagnostic and treatment services, serving as guidance to institutions and policy makers. With regard to clinical practice, there might be cancer-directed treatment options that, although not fully guideline adherent, have relevant survival benefit. Others should perhaps not be chosen even under resource-constrained circumstances.

Breast Cancer Diagnostics, Therapy, and Outcomes in Sub-Saharan Africa: A Population-Based Registry Study.

BACKGROUND: Breast cancer (BC) is the most common cancer in sub-Saharan Africa (SSA). However, little is known about the actual therapy received by women with BC and their survival outcome at the population level in SSA. This study aims to describe the cancer-directed therapy received by patients with BC at the population level in SSA, compare these results with the NCCN Harmonized Guidelines for SSA (NCCN Harmonized Guidelines), and evaluate the impact on survival. METHODS: Random samples of patients with BC (≥40 patients per registry), diagnosed from 2009 through 2015, were drawn from 11 urban population-based cancer registries from 10 countries (Benin, Congo, Cote d'Ivoire, Ethiopia, Kenya, Mali, Mozambique, Namibia, Uganda, and Zimbabwe). Active methods were used to update the therapy and outcome data of diagnosed patients ("traced patients"). Excess hazards of death by therapy use were modeled in a relative survival context. RESULTS: A total of 809 patients were included. Additional information was traced for 517 patients (63.8%), and this proportion varied by registry. One in 5 traced patients met the minimum diagnostic criteria (cancer stage and hormone receptor status known) for use of the NCCN Harmonized Guidelines. The hormone receptor status was unknown for 72.5% of patients. Of the traced patients with stage I-III BC (n=320), 50.9% received inadequate or no cancer-directed therapy. Access to therapy differed by registry area. Initiation of adequate therapy and early-stage diagnosis were the most important determinants of survival. CONCLUSIONS: Downstaging BC and improving access to diagnostics and care are necessary steps to increase guideline adherence and improve survival for women in SSA. It will also be important to strengthen health systems and facilities for data management in SSA to facilitate patient follow-up and disease surveillance.

Cancer in Mozambique: Results from two population-based cancer registries.

Results from two recently established population-based registries in Mozambique are reported: Beira in the central region (2014-2017) and Maputo, the capital city, in the South (2015-2017). The results are compared to those from Maputo (Lourenço Marques at the time) in 1956-1960 (appearing Cancer Incidence in Five Continents Vol 1), and with estimated incidence rates from other regions of Africa. The elevated prevalence of HIV infection (12.6% of adults in 2018) results in high rates for HIV-related cancers, and the greater prevalence in central Mozambique, compared to the south, largely explains the rather higher rates of Kaposi sarcoma (males), non-Hodgkin lymphoma, squamous cell carcinoma of conjunctiva and cervical cancer in Beira than in Maputo. Burkitt lymphoma is the commonest childhood cancer in Beira, with high rates typical of East Africa, while the low rates in Maputo are more typical of Southern Africa. Overall, 44% of cancers in Maputo and 52% in Beira are estimated to be caused by infectious agents. In the last 60 years, cancers more frequent in developed countries, such as breast and prostate, are emerging in Mozambique. The incidence of the former in Maputo has increased fivefold since 1956-1960, that of prostate cancer 2.5-fold, and that of large bowel cancer doubled. The results reported here were used to make national estimates of incidence, mortality and prevalence in Globocan 2018. The two registries were important in providing data to establish priority actions in the National Cancer Control Plan, and are a valuable resource to monitor progress toward its goals.

Cervical cancer survival in sub-Saharan Africa by age, stage at diagnosis and Human Development Index: A population-based registry study.

Cervical cancer is the leading cause of cancer death in African women. We sought to estimate population-based survival and evaluate excess hazards for mortality in African women with cervical cancer, examining the effects of country-level Human Development Index (HDI), age and stage at diagnosis. We selected a random sample of 2760 incident cervical cancer cases, diagnosed in 2005 to 2015 from 13 population-based cancer registries in 11 countries (Benin, Cote d'Ivoire, Ethiopia, Kenya, Mauritius, Mozambique, Namibia, Seychelles, South Africa, Uganda and Zimbabwe) through the African Cancer Registry Network. Of these, 2735 were included for survival analyses. The 1-, 3- and 5-year observed and relative survival were estimated by registry, stage and country-level HDI. We used flexible Poisson regression models to estimate the excess hazards for death adjusting for age, stage and HDI. Among patients with known stage, 65.8% were diagnosed with Stage III-IV disease. The 5-year relative survival for Stage I-II cervical cancer in high HDI registry areas was 67.5% (42.1-83.6) while it was much lower (42.2% [30.6-53.2]) for low HDI registry areas. Independent predictors of mortality were Stage III-IV disease, medium to low country-level HDI and age >65 years at cervical cancer diagnosis. The average relative survival from cervix cancer in the 11 countries was 69.8%, 44.5% and 33.1% at 1, 3 and 5 years, respectively. Factors contributing to the HDI (such as education and a country's financial resources) are critical for cervical cancer control in SSA and there is need to strengthen health systems with timely and appropriate prevention and treatment programmes.

Breast cancer survival in sub-Saharan Africa by age, stage at diagnosis and human development index: A population-based registry study.

Breast cancer is the leading cancer diagnosis and second most common cause of cancer deaths in sub-Saharan Africa (SSA). Yet, there are few population-level survival data from Africa and none on the survival differences by stage at diagnosis. Here, we estimate breast cancer survival within SSA by area, stage and country-level human development index (HDI). We obtained data on a random sample of 2,588 breast cancer incident cases, diagnosed in 2008-2015 from 14 population-based cancer registries in 12 countries (Benin, Cote d'Ivoire, Ethiopia, Kenya, Mali, Mauritius, Mozambique, Namibia, Seychelles, South Africa, Uganda and Zimbabwe) through the African Cancer Registry Network. Of these, 2,311 were included for survival analyses. The 1-, 3- and 5-year observed and relative survival (RS) were estimated by registry, stage and country-level HDI. We equally estimated the excess hazards adjusting for potential confounders. Among patients with known stage, 64.9% were diagnosed in late stages, with 18.4% being metastatic at diagnosis. The RS varied by registry, ranging from 21.6%(8.2-39.8) at Year 3 in Bulawayo to 84.5% (70.6-93.5) in Namibia. Patients diagnosed at early stages had a 3-year RS of 78% (71.6-83.3) in contrast to 40.3% (34.9-45.7) at advanced stages (III and IV). The overall RS at Year 1 was 86.1% (84.4-87.6), 65.8% (63.5-68.1) at Year 3 and 59.0% (56.3-61.6) at Year 5. Age at diagnosis was not independently associated with increased mortality risk after adjusting for the effect of stage and country-level HDI. In conclusion, downstaging breast cancer at diagnosis and improving access to quality care could be pivotal in improving breast cancer survival outcomes in Africa.

Clinical presentation and diagnosis of adult patients with non-Hodgkin lymphoma in Sub-Saharan Africa.

Non-Hodgkin lymphoma (NHL) is the sixth most common cancer in Sub-Saharan Africa (SSA). Comprehensive diagnostics of NHL are essential for effective treatment. Our objective was to assess the frequency of NHL subtypes, disease stage and further diagnostic aspects. Eleven population-based cancer registries in 10 countries participated in our observational study. A random sample of 516 patients was included. Histological confirmation of NHL was available for 76.2% and cytological confirmation for another 17.3%. NHL subclassification was determined in 42.1%. Of these, diffuse large B cell lymphoma, chronic lymphocytic leukaemia and Burkitt lymphoma were the most common subtypes identified (48.8%, 18.4% and 6.0%, respectively). We traced 293 patients, for whom recorded data were amended using clinical records. For these, information on stage, human immunodeficiency virus (HIV) status and Eastern Cooperative Oncology Group Performance Status (ECOG PS) was available for 60.8%, 52.6% and 45.1%, respectively. Stage at diagnosis was advanced for 130 of 178 (73.0%) patients, HIV status was positive for 97 of 154 (63.0%) and ECOG PS was ≥2 for 81 of 132 (61.4%). Knowledge about NHL subclassification and baseline clinical characteristics is crucial for guideline-recommended treatment. Hence, regionally adapted investments in pathological capacity, as well as standardised clinical diagnostics, will significantly improve the therapeutic precision for NHL in SSA.

The Capulana study: a prospective evaluation of cervical cancer screening using human papillomavirus testing in Mozambique.

BACKGROUND: Cervical cancer is the leading cause of cancer and related deaths among women in Mozambique. There is limited access to screening and few trained personnel to manage women with abnormal results. Our objective was to implement cervical cancer screening with human papillomavirus (HPV) testing, with navigation of women with abnormal results to appropriate diagnostic and treatment services. METHODS: We prospectively enrolled women aged 30-49 years living in Maputo, Mozambique, from April 2018 to September 2019. All participants underwent a pelvic examination by a nurse, and a cervical sample was collected and tested for HPV using the careHPV test (Qiagen, Gaithersburg, Maryland, USA). HPV positive women were referred for cryotherapy or, if ineligible for cryotherapy, a loop electrosurgical excision procedure. Women with findings concerning for cancer were referred to the gynecologic oncology service. RESULTS: Participants (n=898) had a median age of 38 years and 20.3% were women living with the human immunodeficiency virus. HPV positivity was 23.7% (95% confidence interval 21.0% to 26.6%); women living with human immunodeficiency virus were twice as likely to test positive for HPV as human immunodeficiency virus negative women (39.2% vs 19.9%, p<0.001). Most HPV positive women (194 of 213, 91.1%) completed all steps of their diagnostic work-up and treatment. Treatment included cryotherapy (n=158, 77.5%), loop electrosurgical excision procedure (n=30, 14.7%), or referral to a gynecologist or gynecologic oncologist (n=5, 2.5%). Of eight invasive cervical cancers, 5 (2.8%) were diagnosed in women living with human immunodeficiency virus and 3 (0.4%) in human immunodeficiency virus negative women (p=0.01). CONCLUSION: Cervical cancer screening with HPV testing, including appropriate follow-up and treatment, was feasible in our study cohort in Mozambique. Women living with human immunodeficiency virus appear to be at a significantly higher risk for HPV infection and the development of invasive cervical cancer than human immunodeficiency virus negative women.

Standardization of Minimally Invasive Tissue Sampling Specimen Collection and Pathology Training for the Child Health and Mortality Prevention Surveillance Network.

BACKGROUND: Minimally invasive tissue sampling (MITS) is a simplified postmortem examination technique that has shown to be an adequate approach for cause of death investigation in low-resource settings. It requires relatively low level of infrastructures and can be performed by health professionals with no background in pathology. A training program has been developed for the Child Health and Mortality Prevention Surveillance (CHAMPS) network to guarantee standardization of specimen collection techniques, procedures, and laboratory methods. METHODS: The training program has included assessment of the site capacities and training on a standardized protocol of MITS sampling and histological processing. The project has also introduced a program of training for trainers for the personnel from Mozambique. To guarantee the adequacy of the procedure in each site, a trainer accompanied the local teams when the activities started. Training outcomes were assessed by evaluating the quality of the samples obtained and the quality of the slides produced locally. RESULTS: Between June 2016 and October 2018, the laboratories of 7 sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) have been evaluated and upgraded. Training has been delivered to 63 staff members from all sites. More than 600 MITS procedures have been performed. The quantity of tissue obtained in the MITS by the local teams was sufficient or abundant in 73%, and 87% of the slides were considered as technically acceptable or excellent. CONCLUSIONS: Satisfactory standardization of MITS and histology procedures has been achieved across all CHAMPS sites through organized capacity-building plans.

Unmasking the hidden tuberculosis mortality burden in a large post mortem study in Maputo Central Hospital, Mozambique.

Sensitive tools are needed to accurately establish the diagnosis of tuberculosis (TB) at death, especially in low-income countries. The objective of this study was to evaluate the burden of TB in a series of patients who died in a tertiary referral hospital in sub-Saharan Africa using an in-house real time PCR (TB-PCR) and the Xpert MTB/RIF Ultra (Xpert Ultra) assay.Complete diagnostic autopsies were performed in a series of 223 deaths (56.5% being HIV-positive), including 54 children, 57 maternal deaths and 112 other adults occurring at the Maputo Central Hospital, Mozambique. TB-PCR was performed in all lung, cerebrospinal fluid and central nervous system samples in HIV-positive patients. All samples positive for TB-PCR or showing histological findings suggestive of TB were analysed with the Xpert Ultra assay.TB was identified as the cause of death in 31 patients: three out of 54 (6%) children, five out of 57 (9%)maternal deaths and 23 out of 112 (21%) other adults. The sensitivity of the main clinical diagnosis to detect TB as the cause of death was 19.4% (95% CI 7.5-37.5) and the specificity was 97.4% (94.0-99.1) compared to autopsy findings. Concomitant TB (TB disease in a patient dying of other causes) was found in 31 additional cases. Xpert Ultra helped to identify 15 cases of concomitant TB. In 18 patients, Mycobacterium tuberculosis DNA was identified by TB-PCR and Xpert Ultra in the absence of histological TB lesions. Overall, 62 (27.8%) cases had TB disease at death and 80 (35.9%) had TB findings.The use of highly sensitive, easy to perform molecular tests in complete diagnostic autopsies may contribute to identifying TB cases at death that would have otherwise been missed. Routine use of these tools in certain diagnostic algorithms for hospitalised patients needs to be considered. Clinical diagnosis showed poor sensitivity for the diagnosis of TB at death.

Validity of a minimally invasive autopsy for cause of death determination in maternal deaths in Mozambique: An observational study.

BACKGROUND: Despite global health efforts to reduce maternal mortality, rates continue to be unacceptably high in large parts of the world. Feasible, acceptable, and accurate postmortem sampling methods could provide the necessary evidence to improve the understanding of the real causes of maternal mortality, guiding the design of interventions to reduce this burden. METHODS AND FINDINGS: The validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in an observational study in 57 maternal deaths by comparing the results of the MIA with those of the gold standard (complete diagnostic autopsy [CDA], which includes any available clinical information). Concordance between the MIA and the gold standard diagnostic categories was assessed by the kappa statistic, and the sensitivity, specificity, positive and negative predictive values and their 95% confidence intervals (95% CI) to identify the categories of diagnoses were estimated. The main limitation of the study is that both the MIA and the CDA include some degree of subjective interpretation in the attribution of cause of death. A cause of death was identified in the CDA in 98% (56/57) of cases, with indirect obstetric conditions accounting for 32 (56%) deaths and direct obstetric complications for 24 (42%) deaths. Nonobstetric infectious diseases (22/32, 69%) and obstetric hemorrhage (13/24, 54%) were the most common causes of death among indirect and direct obstetric conditions, respectively. Thirty-six (63%) women were HIV positive, and HIV-related conditions accounted for 16 (28%) of all deaths. Cerebral malaria caused 4 (7%) deaths. The MIA identified a cause of death in 86% of women. The overall concordance of the MIA with the CDA was moderate (kappa = 0.48, 95% CI: 0.31-0.66). Both methods agreed in 68% of the diagnostic categories and the agreement was higher for indirect (91%) than for direct obstetric causes (38%). All HIV infections and cerebral malaria cases were identified in the MIA. The main limitation of the technique is its relatively low performance for identifying obstetric causes of death in the absence of clinical information. CONCLUSIONS: The MIA procedure could be a valuable tool to determine the causes of maternal death, especially for indirect obstetric conditions, most of which are infectious diseases. The information provided by the MIA could help to prioritize interventions to reduce maternal mortality and to monitor progress towards achieving global health targets.

Validity of a minimally invasive autopsy for cause of death determination in stillborn babies and neonates in Mozambique: An observational study.

BACKGROUND: Over 5 million stillbirths and neonatal deaths occur annually. Limited and imprecise information on the cause of these deaths hampers progress in achieving global health targets. Complete diagnostic autopsies (CDAs)-the gold standard for cause of death determination-are difficult to perform in most high-burden settings. Therefore, validation of simpler and more feasible methods is needed. METHODS AND FINDINGS: In this observational study, the validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in 18 stillbirths and 41 neonatal deaths by comparing the results of the MIA with those of the CDA. Concordance between the categories of diseases obtained by the 2 methods was assessed by the Kappa statistic, and the sensitivity, specificity, positive, and negative predictive values of the MIA diagnoses were calculated. A cause of death was identified in 16/18 (89%) and 15/18 (83%) stillborn babies in the CDA and the MIA, respectively. Fetal growth restriction accounted for 39%, infectious diseases for 22%, intrapartum hypoxia for 17%, and intrauterine hypoxia for 11% of stillborn babies. Overall, the MIA showed in this group a substantial concordance with the CDA (Kappa = 0.78, 95% CI [0.56-0.99]). A cause of death was identified in all (100%) and 35/41 (85%) neonatal deaths in the CDA and the MIA, respectively. In this group, the majority of deaths were due to infectious diseases (66%). The overall concordance of the MIA with the CDA in neonates was moderate (Kappa = 0.40, 95% CI [0.18-0.63]). A high percentage of accuracy was observed for the MIA in all the diagnostic categories in both stillbirths and neonates (>75%). The main limitation of this study is that some degree of subjective interpretation is inherent to cause-of-death attribution in both the MIA and the CDA; this is especially so in stillbirths and in relation to fetal growth restriction. CONCLUSIONS: The MIA could be a useful tool for cause-of-death determination in stillbirths and neonatal deaths. These findings may help to accelerate progress towards meeting global health targets by obtaining more accurate information on the causes of death in these age groups, which is essential in guiding the design of new interventions and increasing the effectiveness of those already implemented.