Continuing Professional Development Program in Health Facilities in Rwanda: A Qualitative Study on the Perceptions of Health Professionals.

Background: Continuous professional development (CPD) is an important pillar in healthcare service delivery. Health professionals at all levels and disciplines must continuously update their knowledge and skills to cope with increasing professional demands in the context of a continuously changing spectrum of diseases. This study aimed to assess the CPD programs available in healthcare facilities (HFs) in Rwanda. Methodology: Semi-structured interviews were conducted using purposive sampling. Accordingly, the respondents belonged to different categories of health professionals, namely nurses, midwives, laboratory technicians, pharmacists, general practitioners, and specialist doctors. Thirty-five participants from district, provincial, and national referral hospitals were interviewed between September and October 2020. A thematic analysis was conducted using Atlas ti.7.5.18, and the main findings for each theme were reported as a narrative summary. Results: The CPD program was reported to be available, but not for all HPs and HFs, because of either limited access to online CPD programs or limited HF leaders. Where available, CPD programs have sometimes been reported to be irrelevant to health professionals and patients' needs. Furthermore, the planning and implementation of current CPD programs seldom involves beneficiaries. Some HFs do not integrate CPD programs into their daily activities, and current CPD programs do not accommodate mentorship programs. The ideal CPD program should be designed around HPs and service needs and delivered through a user-friendly platform. The motivators for HPs to engage in CPD activities include learning new things that help them improve their healthcare services and license renewal. Conclusion: This study provides an overview of the status and perceptions of the CPD program in HFs in Rwanda and provides HPs' insights on the improvements in designing a standardized and harmonized CPD program in Rwanda.

The spectrum of TP53 mutations in Rwandan patients with gastric cancer.

BACKGROUND: Gastric cancer is the sixth most frequently diagnosed cancer and third in causing cancer-related death globally. The most frequently mutated gene in human cancers is TP53, which plays a pivotal role in cancer initiation and progression. In Africa, particularly in Rwanda, data on TP53 mutations are lacking. Therefore, this study intended to obtain TP53 mutation status in Rwandan patients with gastric cancer. RESULTS: Formalin-fixed paraffin-embedded tissue blocks of 95 Rwandan patients with histopathologically proven gastric carcinoma were obtained from the University Teaching Hospital of Kigali. After DNA extraction, all coding regions of the TP53 gene and the exon-intron boundary region of TP53 were sequenced using the Sanger sequencing. Mutated TP53 were observed in 24 (25.3%) of the 95 cases, and a total of 29 mutations were identified. These TP53 mutations were distributed between exon 4 and 8 and most of them were missense mutations (19/29; 65.5%). Immunohistochemical analysis for TP53 revealed that most of the TP53 missense mutations were associated with TP53 protein accumulation. Among the 29 mutations, one was novel (c.459_477delCGGCACCCGCGTCCGCGCC). This 19-bp deletion mutation in exon 5 caused the production of truncated TP53 protein (p.G154Wfs*10). Regarding the spectrum of TP53 mutations, G:C > A:T at CpG sites was the most prevalent (10/29; 34.5%) and G:C > T:A was the second most prevalent (7/29; 24.1%). Interestingly, when the mutation spectrum of TP53 was compared to three previous TP53 mutational studies on non-Rwandan patients with gastric cancer, G:C > T:A mutations were significantly more frequent in this study than in our previous study (p = 0.013), the TCGA database (p = 0.017), and a previous study on patients from Hong Kong (p = 0.006). Even after correcting for false discovery, statistical significance was observed. CONCLUSIONS: Our results suggested that TP53 G:C > T:A transversion mutation in Rwandan patients with gastric cancer is more frequent than in non-Rwandan patients with gastric cancer, indicating at an alternative etiological and carcinogenic progression of gastric cancer in Rwanda.

Clinicopathological Characteristics and Mutational Landscape of APC, HOXB13, and KRAS among Rwandan Patients with Colorectal Cancer.

Cancer research in Rwanda is estimated to be less than 1% of the total African cancer research output with limited research on colorectal cancer (CRC). Rwandan patients with CRC are young, with more females being affected than males, and most patients present with advanced disease. Considering the paucity of oncological genetic studies in this population, we investigated the mutational status of CRC tissues, focusing on the Adenomatous polyposis coli (APC), Kirsten rat sarcoma (KRAS), and Homeobox B13 (HOXB13) genes. Our aim was to determine whether there were any differences between Rwandan patients and other populations. To do so, we performed Sanger sequencing of the DNA extracted from formalin-fixed paraffin-embedded adenocarcinoma samples from 54 patients (mean age: 60 years). Most tumors were located in the rectum (83.3%), and 92.6% of the tumors were low-grade. Most patients (70.4%) reported never smoking, and 61.1% of patients had consumed alcohol. We identified 27 variants of APC, including 3 novel mutations (c.4310_4319delAAACACCTCC, c.4463_4470delinsA, and c.4506_4507delT). All three novel mutations are classified as deleterious by MutationTaster2021. We found four synonymous variants (c.330C>A, c.366C>T, c.513T>C, and c.735G>A) of HOXB13. For KRAS, we found six variants (Asp173, Gly13Asp, Gly12Ala, Gly12Asp, Gly12Val, and Gln61His), the last four of which are pathogenic. In conclusion, here we contribute new genetic variation data and provide clinicopathological information pertinent to CRC in Rwanda.

The use of Vsee videoconferencing for live telepathology in Rwanda, a potential solution for resource-limited area.

Objective: The shortage of pathologists is a worldwide problem that is more severe in Africa. One of the solutions is the use of telepathology (TP); however, most of the TP systems are expensive and unaffordable in many developing countries. At the University Teaching Hospital of Kigali, Rwanda, we assessed the possibility of combining commonly available laboratory tools into a system that can be used for diagnostic TP using Vsee videoconferencing. Methodology: Using an Olympus microscope (with a camera) operated by a laboratory technologist, histologic images were transmitted to a computer whose screen was shared, using Vsee, with a remotely located pathologist who made the diagnoses. Sixty consecutive small biopsies (≤6 glass slides) from different tissues were examined to make a diagnosis using live Vsee-based videoconferencing TP. Vsee-based diagnoses were compared to pre-existing light microscopy-based diagnoses. Percent agreement and unweighted Cohen's kappa coefficient of the agreement were calculated. Results: For agreement between conventional microscopy-based and Vsee-based diagnoses, we found an unweighted Cohen's kappa of 0.77 ± 0.07SE with a 95% CI of 0.62-0.91. The perfect percent agreement was 76.6% (46 of 60). Agreement with minor discrepancy was 15% (9 of 60). There were 2 cases of major discrepancy (3.30%). We were unable to make a diagnosis in 3 cases (5%) because of poor image quality related to the instantaneous internet connectivity problems. Conclusion: This system provided promising results. However, additional studies to assess other parameters which can affect its performance are needed before this system can be considered an alternative method of providing TP services in resource-limited settings.

Teaching Infectious Disease Pathology and Taking it To Africa.

With the advent of increasing emerging infectious diseases, rising antibiotic resistance, and the growing number of immunocompromised patients, there is increasing demand for infectious disease (ID) pathology expertise and microbiology testing. Currently, ID pathology training and emerging molecular microbiology techniques (eg, metagenomic next-generation sequencing and whole genome sequencing) are not included in the most American Council of Graduate Medical Education medical microbiology fellowship curricula, and not surprisingly, many institutions lack anatomical pathologists with expertise in ID pathology and advanced molecular diagnostics. In this article, we describe the curriculum and structure of the Franz von Lichtenberg Fellowship in Infectious Disease and Molecular Microbiology at Brigham and Women's Hospital in Boston, MA. We emphasize the value of a training model that strives to integrate anatomical pathology, clinical pathology, and molecular pathology by providing examples in a case-based format and presenting selected metrics of the potential effect of such integrative ID pathology service and briefly describing opportunities and challenges of our global health efforts in Rwanda.

Pathological Characteristics, Prognostic Determinants and the Outcome of Patients Diagnosed with Colorectal Adenocarcinoma at the University Teaching Hospital of Kigali.

Worldwide, colorectal cancer (CRC) is the second most diagnosed cancer in female and the third in men, arising from the epithelium of the colorectum. It is known that colorectal cancer is common in developed countries than in developing countries which may be due to inaccurate data on the existence of the disease in that region combined with embracing western lifestyle expressed by the current trend of changes in cultural, social, and lifestyle practices playing a major part in the etiology of CRC. The aim of this study was to document epidemiological, pathological characteristics, and prognostics determinants of patients diagnosed with CRC in Rwanda. The data from patients' files and reviewed glass slides for 101 cases all from Kigali University Teaching Hospital (CHUK) were statistically analyzed and patient characteristics were described as mean and frequency accordingly. Comparisons were performed using chi square tests, Fisher's exact test and odds ratio with 95% confidence interval (CI). Survival curves were plotted using the Kaplan-Meier method, and log-rank test was used to assess the statistical differences in the observed survival curves by each categorical variable. A P value < 0.05 was considered statistically significant. Statistical analyses were performed using Statistical Product and Service Solutions (SPSS), GraphPad Prism, and MedCalc, accordingly. Mean age of the participants was 54.26 years, the main symptom was rectal bleeding (46.5%), rectal adenocarcinoma NOS represented 40.6%, conventional adenocarcinoma was 60.4%, most tumors were of Grade II (54.5%), most common stage was pT3N0 (20.8%), resection margins were free at 71.3%, lympho-vascular invasion was 49.5% of cases, a high immune response was in 71.3% of cases and of 101cases, and 55.4% were still alive at the end of the data collection, with 29.3% of patients have overall survival of 5 years. Prognostic determinants also affect the outcome in this study and overall survival period was 3 years for CRC diagnosed in Rwanda.

Knowledge, Barriers and Motivators to Cervical Cancer Screening in Rwanda: A Qualitative Study.

Background: Cervical cancer is a global public health problem with marked geographical disparity. High morbidity and mortality rates in developing countries are associated with low screening rates. In 2020, in Rwanda, 3.7 million women aged 15-59 years were at risk of developing cervical cancer, the most commonly diagnosed female cancer in Rwanda. Despite Rwanda being the first African country to vaccinate against human papilloma virus with a three-dose regimen vaccination coverage of nearly 93% in the target population of girls aged <15 years, and having established cervical cancer screening program, recent studies have found low screening rates. Our study sought to determine knowledge, motivators and barriers of cervical cancer screening. Methods: We conducted a qualitative descriptive study; using focus group interview in an urban health facility (Muhima district hospital) and a rural health center (Nyagasambu health center) offering cervical screening services in Rwanda. Participants were women seeking these services and other women attending the health facility for any reason, and female staff working in these facilities. Interviews were recorded and transcribed, and data were analyzed using content analysis. Results: Thirty women participated in focus group interview, with an average age of 39 years. Many of women showed knowledge about cervical cancer existence and prevention methods. However, fear for pain, lack of knowledge about screening, how and where the screening was done, and concern for privacy were recurring subthemes. Some participants also mentioned lack of health insurance as a barrier for cervical cancer screening. Conclusion: Barriers to uptake cervical cancer screening services in Rwanda are related to poor information about cervical cancer and the importance of screening as well as non-adherence to medical insurance. Population sensitization through campaign and community outreach activities could have a positive impact on increasing the usage of cervical cancer screening in Rwanda.

Experience and Perception of Patients and Healthcare Professionals on Acute Leukemia in Rwanda: A Qualitative Study.

Purpose: To explore challenges associated with the timely diagnosis, therapy, and prognosis of acute leukemia in Rwanda. Methods: This is a qualitative study using a phenomenological approach that involved patients, patients' guardians, and healthcare professionals such as physicians from district hospitals and specialists from referral hospitals, as well as healthcare administrators. The primary data were collected from district and referral hospitals and central healthcare administration in Rwanda. The data were collected between July and October 2019. In-depth interviews were conducted, and thematic analysis was employed to interpret the results. Results: We identified barriers to seeking healthcare such as (i) insufficient knowledge within the population may lead patients and their guardians to consult traditional healers before seeking qualified medical care, and (ii) financial constraints that preclude payment of healthcare fees or other out-of-pocket cost related to diagnosis and treatment. We also observed that the referral system is tedious and primary healthcare facilities lack the competence and resources for the necessary diagnostic practices. Both may further delay diagnosis and therapy. Accordingly, healthcare professionals at the referral hospitals stated that most patients were seen at an advanced stage of the disease. For the treatment of acute lymphoblastic leukemia (ALL), only chemotherapy is utilized in Rwanda, while bone marrow (BM) transplantation is not available. Palliation is the only available treatment for the vast majority of Rwandan acute myeloid leukemia (AML) patients. Conclusion: ALL and AML are likely under-reported in Rwanda and diagnosis may be delayed, which may be explained by patient-related factors (lack of knowledge, financial constraints), a tedious referral system, and suboptimal diagnostic resources.

Building Capacity and Infrastructure at Hospitals Implementing Minimally Invasive Tissue Sampling: Experience and Lessons Learned From Nepal, Rwanda, and Tanzania.

BACKGROUND: Minimally invasive tissue sampling (MITS) is a useful tool to determine cause of death in low- and middle-income countries (LMICs). In 2019 the MITS Surveillance Alliance supported the implementation of small-scale postmortem studies using MITS in several LMICs. METHODS: In this article we describe the preparations, challenges, and lessons learned as part of implementing MITS across 4 study sites in 3 countries: Nepal, Rwanda, and Tanzania. We describe the process for building capacity to conduct MITS, which consisted of training in MITS sample collection, individual site assessment to determine readiness and gaps prior to implementation, site visits as sites began implementation of MITS, and feedback based on remote evaluation of histology slides via an online portal. RESULTS: The 4 study sites each conducted 100 MITS, for a total of 400. All 4 sites lacked sufficient infrastructure and facilities to conduct MITS, and upgrades were required. Common challenges faced by sites included that clinical autopsies were neither routinely conducted nor widely accepted. Limited clinical records made cause of death determination more difficult. Lessons learned included the importance of sensitization of the community and medical staff to MITS to enhance understanding and increase consent. CONCLUSIONS: The study sites accomplished MITS and utilized the available support systems to overcome the challenges. The quality of the procedures was satisfactory and was facilitated through the organized capacity-building programs.

Exploring Perceptions and Acceptance of Minimally Invasive Tissue Sampling among Bereaved Relatives and Health-Care Professionals in Rwanda.

PURPOSE: In most low- and lower middle-income countries (LMICs), minimally invasive tissue sampling (MITS) is a relatively new procedure for identifying the cause of death (CoD). This study aimed to explore perceptions and acceptance of bereaved families and health-care professionals regarding MITS in the context of MITS initiation in Rwanda as an alternative to clinical autopsy. METHODS: This was a qualitative phenomenological study with thematic analysis. Participants were bereaved relatives (individual interviews) and health-care professionals (focus-group discussions) involved in MITS implementation. It was conducted in the largest referral and teaching hospital in Rwanda. RESULTS: Motivators of MITS acceptance included eagerness to know the CoD, noninvasiveness of MITS, trust in medics, and the fact that it was free. Barriers to consent to MITS included inadequate explanations from health-care professionals, high socioeconomic status, lack of power to make decisions, and lack of trust in medics. Health-care professionals perceived both conventional autopsy and MITS as gold-standard procedures in CoD determination. They recommended including MITS among hospital services and commended the post-MITS multidisciplinary discussion panel in CoD determination. They pointed out that there might be reticence in approaching bereaved relatives to obtain consent for MITS. Both groups of participants highlighted the issue of delay in releasing MITS results. CONCLUSION: Both health-care professionals and bereaved relatives appreciate that MITS is an acceptable procedure to include in routine hospital services. Dealing with barriers met by either group is to be considered in the eventual next phases of MITS implementation in Rwanda and similar sociocultural contexts.

Premenopausal Breast Cancer Risk Factors and Associations with Molecular Subtypes: A Case-Control Study.

BACKGROUND: Breast cancer (BC) is the most prevalent cancer in women and the leading cause of women's cancer-related deaths and morbidity worldwide. In Rwanda, BC incidence is increasing with an unacceptably high mortality rate in premenopausal women. OBJECTIVES: The purpose was to identify modifiable BC risk factors and assess associations between common breast cancer risks factors and molecular subtypes in premenopausal women in Rwanda. METHODS: This was a case-control study. Premenopausal women with histological confirmation of BC and frequency-matched for age controls were recruited. A preestablished questionnaire was administered to both cases and controls for sociodemographics, BC probable risk factors, and clinical and pathological characteristics. BC was classified into luminal A, luminal B, HER2-type, basal-like (triple negative), and unclassified molecular subtypes by immunohistochemistry (IHC). Odds ratio (OR) and 95% confidence interval (CI) were estimated using multivariate logistic regression analysis. RESULTS: 340 participants were recruited into the study (170 cases vs. 170 controls). The median age was 39 years. The majority of cases presented at advanced stages of the disease (51.2% in stages III and IV) and had invasive ductal carcinoma (98.2%). 60.6% had subtypes of poor prognosis (HER2 enriched 14.7%, triple negative 12.9%, and unclassified 32.9%). Alcohol intake (AOR = 3.73, 95%CI 2.19 - 6.32, p < 0.001), obesity/overweight in adolescence or early adulthood (AOR = 10.86, 95%CI 4.82 - 24.4, p < 0.001), history of primary infertility (AOR = 33.8, 95%CI 3.5 - 321.5, p = 0.002), nulliparity (AOR = 3.75, 95%CI 1.61 - 8.75, p = 0.002), and a history of benign breast disease (AOR = 6.06, 95%CI 1.19 - 30.73, p = 0.03) were associated with the occurrence of premenopausal breast cancer. There was no significant difference between risk factor stratification per molecular subtype. CONCLUSION: Several reproductive, environmental, and lifestyle risk factors have been identified to be associated with premenopausal BC. Among them, alcohol intake and obesity/overweight during adolescence/early adulthood can be modified. Interventions targeting alcohol consumption and obesity/overweight in adolescents and young adults may decrease the incidence of premenopausal breast cancer.

Use of the Xpert Breast Cancer STRAT4 for Biomarker Evaluation in Tissue Processed in a Developing Country.

OBJECTIVES: Breast cancer immunohistochemistry (IHC) biomarker testing is limited in low-resource settings, and an alternative solution is needed. A point-of-care mRNA STRAT4 breast cancer assay for ESR1, PGR, ERBB2, and MKi67, for use on the GeneXpert platform, has been recently validated on tissues from internationally accredited laboratories, showing excellent concordance with IHC. METHODS: We evaluated STRAT4/IHC ESR1/estrogen receptor (ER), ERBB2/human epidermal growth factor receptor 2 (HER2) concordance rates of 150 breast cancer tissues processed in Rwanda, with undocumented cold ischemic and fixation time. RESULTS: Assay fail/indeterminate rate was 2.6% for ESR1 and ERBB2. STRAT4 agreement with ER IHC was 92.5% to 93.3% and 97.8% for HER2, for standard (1x) and concentrated (4x) reagent-conserving protocols, respectively. Eleven of 12 discordant ER/ESR1 cases were ESR1- negative/IHC-positive. These had low expression of ER by IHC in mostly very small tumor areas tested (7/12; <25 mm2). In two of three discordant HER2 cases, the STRAT4-ERBB2 result correlated with the subsequent fluorescence in situ hybridization (FISH) result. STRAT4-ERBB2 results in 9 of 10 HER2-IHC equivocal cases were concordant with FISH. CONCLUSIONS: The STRAT4 assay is an alternative for providing quality-controlled breast cancer biomarker data in laboratories unable to provide quality and/or cost-efficient IHC services.

Occurrence of Helicobacter Pylori in Specimens of Chronic Gastritis and Gastric Adenocarcinoma Patients: A Retrospective Study at University Teaching Hospital, Kigali, Rwanda.

INTRODUCTION: Helicobacter pylori (H. pylori) infection is the major cause of gastroduodenal diseases in populations of different ages. We conducted aretrospective studyusing archived tissue samples to determine the prevalence of H. pylori infection among patients diagnosed with gastritis and gastric adenocarcinoma by histopathology cases in one hospital in Rwanda. MATERIALS AND METHODS: Cases of chronic gastritis and gastric adenocarcinoma histologically diagnosed in a tertiary hospital in Rwanda over the period of 2016-2018 were studied for the presence of H. pylori using immunohistochemistry. Diagnosis of positive cases considered immunoreactivity as well as bacterial morphology, including spiral, rod-shaped, angulated and coccoid forms. RESULTS: Three hundred and seven cases were included in this study; chronic gastritis and gastric adenocarcinoma representing 39% and 61%, respectively. The overall frequency of H. pylori infection was 77.5% (80% among chronic gastritis cases versus 76% among gastric adenocarcinoma cases). Prevalence of H. pylori infection in chronic gastritis and adenocarcinoma did not significantly associate with age and sex. CONCLUSION: The prevalence of H. pylori was high among chronic gastritis and gastric adenocarcinoma cases in Rwanda. Pathologists should investigate the presence of H. pylori in gastric biopsies. Our data shows immunohistochemistry method is feasible and adequate to facilitate detection of H. pylori, which may guide timely treatment.

Pathology Characteristics of Lymphomas in Rwanda: A Retrospective Study.

BACKGROUND: Lymphomas have been a global challenge for many decades and despite measures for prevention and management, the incidence continues to increase. There are two main categories, which are Non-Hodgkin's Lymphomas and Hodgkin's Lymphomas and most common etiologies are environmental, genetic alteration, radiation and some viruses. OBJECTIVE: To describe pathology characteristics of lymphomas in Rwanda based on Hematoxylin and Eosin stained glass slides and immuno histo chemistry, and classify them according to clinical aggressiveness. PATIENTS AND METHODS: We conducted a retrospective observational and descriptive study from January 2013 to December 2019. Lymphoma cases were retrieved together with relevant clinical and pathological information, and reviewed by independent pathologists. Histological diagnosis was classified according to the 2008 World Health Organization system in order to assign clinical aggressiveness of the lymphoma. RESULTS: Three hundred and six lymphoma cases were enrolled. Males contributed to 57% of all reviewed case, and slightly over 50% were young aged ≤35 years. Approximately 191 (62%) of cases were nodal lymphomas. Approximately one fifth (18%) of lymphoma cases were HIV positive. Most 213(70%) cases were Non-Hodgkin's Lymphomas of aggressive forms 164(77%). Among 164 cases of aggressive Non-Hodgkin's Lymphomas, diffuse large B cell lymphoma was the leading subtype 91(55.5%), followed by solid lymphoblastic lymphoma 32(19.5%) and Burkitt lymphoma 17(10.4%). Among all Hodgkin lymphoma cases, 90(97%) were classical Hodgkin lymphomaof nodular sclerosis subtype. Hodgkin lymphoma patients were younger compared to Non-Hodgkin's Lymphomas patients (mean age of 24.78±16.3 years versus 38.6±22. 5years, p=.000). CONCLUSION: Substantial proportion of Lymphomapatients in Rwanda were also HIV positive. Interestingly, Non-Hodgkin's Lymphomas in Rwanda are predominated by the most aggressive forms, and these mostly affect a younger population. Optimal characterisation of such cases, using advanced methods, is recommended.

Metaplastic Carcinoma of the Breast with Squamous Differentiation: A Case Report from the University Teaching Hospital of Kigali (CHUK), Rwanda.

Metaplastic breast carcinoma is a rare and aggressive condition, accounting less than 1% of breast malignancies. It presents with large mass and frequently with distant metastasis at time of diagnosis. Morphologically, it is characterized by the differentiation of neoplastic epithelium into epithelial or mesenchymal-looking elements like squamous cells, spindle cells, cartilage, or bone and has poor prognosis with its triple negative status.

State of Cancer Control in Rwanda: Past, Present, and Future Opportunities.

Rwanda is a densely populated low-income country in East Africa. Previously considered a failed state after the genocide against the Tutsi in 1994, Rwanda has seen remarkable growth over the past 2 decades. Health care in Rwanda is predominantly delivered through public hospitals and is emerging in the private sector. More than 80% of patients are covered by community-based health insurance (Mutuelle de Santé). The cancer unit at the Rwanda Biomedical Center (a branch of the Ministry of Health) is responsible for setting and implementing cancer care policy. Rwanda has made progress with human papillomavirus (HPV) and hepatitis B vaccination. Recently, the cancer unit at the Rwanda Biomedical Center launched the country's 5-year National Cancer Control Plan. Over the past decade, patients with cancer have been able to receive chemotherapy at Butaro Cancer Center, and recently, the Rwanda Cancer Center was launched with 2 linear accelerator radiotherapy machines, which greatly reduced the number of referrals for treatment abroad. Palliative care services are increasing in Rwanda. A cancer registry has now been strengthened, and more clinicians are becoming active in cancer research. Despite these advances, there is still substantial work to be done and there are many outstanding challenges, including the need to build capacity in cancer awareness among the general population (and shift toward earlier diagnosis), cancer care workforce (more in-country training programs are needed), and research.

Human papillomavirus genotypes in cervical and other HPV-related anogenital cancer in Rwanda, according to HIV status.

The study aim was to describe human papillomavirus (HPV)-attributable cancer burden in Rwanda, according to anogenital cancer site, HPV type, age and HIV status. Tissue specimens of cervical, vulvar, vaginal, penile and anal cancer diagnosed in 2012-2018 were retrieved from three cancer referral hospitals and tested for high-risk (HR) HPV DNA. Cervical cancer represented the majority of cases (598 of 738), of which 96.0% were HR-HPV positive. HPV-attributable fractions in other cancer sites varied from 53.1% in 81 penile, through 76.7% in 30 vulvar, 83.3% in 24 vaginal, up to 100% in 5 anal cases. HPV16 was the predominant HR-HPV type in cervical cancer (55.0%), followed by HPV18 (16.6%) and HPV45 (13.4%). HPV16 also predominated in other cancer sites (60-80% of HR-HPV-attributable fraction). For cervical cancer, type-specific prevalence varied significantly by histology (higher alpha-9 type prevalence in 509 squamous cell carcinoma vs. higher alpha-7 type prevalence in 80 adenocarcinoma), but not between 501 HIV-negative and 97 HIV-positive cases. With respect to types targeted, and/or cross-protected, by HPV vaccines, HPV16/18 accounted for 73%, HPV31/33/45/52/58 for an additional 22% and other HR-HPV types for 5%, of HPV-attributable cancer burden, with no significant difference by HIV status nor age. These data highlight the preventive potential of the ongoing national HPV vaccination program in Rwanda, and in sub-Saharan Africa as a whole. Importantly for this region, the impact of HIV on the distribution of causal HPV types was relatively minor, confirming type-specific relevance of HPV vaccines, irrespective of HIV status.

IFNL4 Genotypes Predict Clearance of RNA Viruses in Rwandan Children With Upper Respiratory Tract Infections.

Polymorphisms in the interferon lambda gene locus (IFNL) such as the IFNL4 genetic variants rs12979860 and rs368234815 are predictive of resolution of hepatitis C virus infection, but information about the impact of these variants in other infections is scarce. This study aimed at determining the potential impact of IFNL4 variation for the clearance of respiratory tract pathogens in Rwandan children (≤5 years old, n = 480) seeking medical care for acute respiratory infections. Nasopharyngeal swabs were retrieved from all children at the first hospital referral and from 161 children at follow-up visits 2 weeks later. The swabs were analyzed for pathogens by real-time PCR and for host cell IFNL4 genotype at rs12979860 and rs368234815. Approximately 1/3 of the children were homozygous for the rs12979860 T allele and the rs368234815 ΔG allele, which are overrepresented in subjects of African descent. These IFNL4 variants were significantly associated with reduced clearance of RNA viruses. Our results suggest that IFNL4 genotypes that are common among subjects of African descent may determine inefficacious clearance of RNA viruses from the respiratory tract.