A cervical cancer biorepository for pharmacogenomics research in Zimbabwe.

BACKGROUND: Research infrastructures such as biorepositories are essential to facilitate genomics and its growing applications in health research and translational medicine in Africa. Using a cervical cancer cohort, this study describes the establishment of a biorepository consisting of biospecimens and matched phenotype data for use in genomic association analysis and pharmacogenomics research. METHOD: Women aged > 18 years with a recent histologically confirmed cervical cancer diagnosis were recruited. A workflow pipeline was developed to collect, store, and analyse biospecimens comprising donor recruitment and informed consent, followed by data and biospecimen collection, nucleic acid extraction, storage of genomic DNA, genetic characterization, data integration, data analysis and data interpretation. The biospecimen and data storage infrastructure included shared -20 °C to -80 °C freezers, lockable cupboards, secured access-controlled laptop, password protected online data storage on OneDrive software. The biospecimen or data storage, transfer and sharing were compliant with the local and international biospecimen and data protection laws and policies, to ensure donor privacy, trust, and benefits for the wider community. RESULTS: This initial establishment of the biorepository recruited 410 women with cervical cancer. The mean (± SD) age of the donors was 52 (± 12) years, comprising stage I (15%), stage II (44%), stage III (47%) and stage IV (6%) disease. The biorepository includes whole blood and corresponding genomic DNA from 311 (75.9%) donors, and tumour biospecimens and corresponding tumour DNA from 258 (62.9%) donors. Datasets included information on sociodemographic characteristics, lifestyle, family history, clinical information, and HPV genotype. Treatment response was followed up for 12 months, namely, treatment-induced toxicities, survival vs. mortality, and disease status, that is disease-free survival, progression or relapse, 12 months after therapy commencement. CONCLUSION: The current work highlights a framework for developing a cancer genomics cohort-based biorepository on a limited budget. Such a resource plays a central role in advancing genomics research towards the implementation of personalised management of cancer.

Recurrent squamous cell carcinoma of the skin treated with immunotherapy.

Squamous cell carcinoma (SCC) has a good prognosis, while metastatic tumors have aggressive behavior. Immunotherapy has become a standard line of treatment in metastatic cancers; pembrolizumab has shown promising results and improved quality of life in recurrent and metastatic cancers. We report a case of recurrent SCC of the skin with extensive disease and a known case of human immunodeficiency virus. He completed standard lines of treatment and currently on immunotherapy. After 3 cycles of immunotherapy plus chemotherapy, he got a complete metabolic response. Our experience showed palliative benefits and increased quality of life.

Cervical cancer management in Zimbabwe (2019-2020).

BACKGROUND: Globally, cervical cancer is the fourth most commonly diagnosed cancer amongst women, and it is especially common in low- and middle-income countries (LMICs). The aim of the study was to determine the current patterns and characteristics of CC management in Zimbabwe in the HIV pandemic era, including the knowledge, attitude and practice of patience. METHODS: The study was a mixed method which incorporated a cross-sectional survey of 408 CC patients which was conducted from October 2019 to September 2020 using an interviewer administered paper questionnaire. The study was conducted at Parirenyatwa hospital, the only cancer treating public health facility in Harare, Zimbabwe. Differences in study outcome by categorical variables were assessed using the Person Chi-square (χ2) test. Odds ratios (unadjusted and adjusted) and 95%CIs for potential risk factors associated with the outcome were estimated using logistic regression model. RESULTS: From a total of 408 CC patients recruited into the study no prevention mechanism was available or known to these patients and only 13% knew that CC is caused by Human papillomavirus. Only 87 (21%) had ever been screened for CC and 83 (97%) of those who had been screened had the visual inspection with acetic acid procedure done. Prevention (screening uptake) is statistically high among the educated (with secondary education OR = 9.497, 95%CI: 2.349-38.390; with tertiary OR = 59.381, 95%CI: 11.937-295.380). Late presentation varied statistically significantly with marital status (high among the divorced, OR = 2.866; 95% CI: 1.549-5.305 and widowed OR = 1.997; 95% CI: 1.112-3.587), was low among the educated (Tertiary OR = .393; 95% CI: .166-.934), low among those living in the rural (OR = .613; 95% CI: .375-.987), high among those with higher parity OR = 1.294; 95% CI: 1.163-1.439). Less than 1% of the patients had surgery done as a means of treatment. Radiotherapy was administered to 350 (86%) of the patients compared to chemotherapy administered to 155 (38%). A total of 350 (86%) have failed to take medication due to its unavailability, while 344 (85%) missed taking medication due to unaffordability. Complementary and alternative medicines were utilized by 235 (58%). Majority, 278 (68%) were HIV positive, mainly pronounced within age (36-49 years OR = 12.673; 95% CI: 2.110-76.137), among those with higher education (secondary education OR = 4.981; 95%CI: 1.394-17.802 and in those with no co-morbidities (893.956; 95%CI: 129.611-6165.810). CONCLUSION: CC management was inadequate from prevention, screening, diagnosis, treatment and palliative care hence there is need to improve CC management in Zimbabwe if morbidity and mortality are to be reduced to acceptable levels. Education helped improve prevention, but reduces chances of diagnosis, working as a doubled edged sword in CC management Prevention was high among the educated. Those in rural areas experience poor CC management. It should be noted that general education is good; however it must be complimented by CC awareness to improve CC management outcomes holistically. Cervical cancer management services need to be decentralized so that those in rural areas have easy access. Given that those with co-morbidities and high parity have better CC management, CC services need to be tied to co-morbidity and antenatal/post-natal care and management services.

Mapping Evidence on Management of Cervical Cancer in Sub-Saharan Africa: Scoping Review.

Cervical cancer (CC) is the most common viral infection of the reproductive tract and in Sub-Saharan Africa (SSA), its morbidity and mortality rates are high. The aim of this review was to map evidence on CC management in SSA. The scoping review was conducted in accordance with Arksey and O'Malley's scoping review framework. The review included studies on different aspects of CC management. The review was also done following the steps and guidelines outlined in the PRISMA-Extension for Scoping Reviews (PRISMA-ScR) checklist. The following databases were searched: PubMed, EBSCOhost, Scopus and Cochrane Database of Systematic Review. A total of 1121 studies were retrieved and 49 which were eligible for data extraction were included in the review. The studies were classifiable in 5 groups: 14 (28.57%) were on barriers to CC screening, 10 (20.41%) on factors associated with late-stage presentation at diagnosis, 11 (22.45%) on status of radiotherapy, 4 (8.20%) on status of chemotherapy and 10 (20.41%) on factors associated with high HPV coverage. High HPV vaccine coverage can be achieved using the class school-based strategy with opt-out consent form process. Barriers to CC screening uptake included lack of knowledge and awareness and unavailability of screening services. The reasons for late-stage presentation at diagnosis were unavailability of screening services, delaying whilst using complementary and alternative medicines and poor referral systems. The challenges in chemotherapy included unavailability and affordability, low survival rates, treatment interruption due to stock-outs as well as late presentation. Major challenges on radiotherapy were unavailability of radiotherapy, treatment interruption due to financial constraints, and machine breakdown and low quality of life. A gap in understanding the status of CC management in SSA has been revealed by the study implying that, without full knowledge of the extent of CC management, the challenges and opportunities, it will be difficult to reduce infection, improve treatment and palliative care. Research projects assessing knowledge, attitude and practice of those in immediate care of girls at vaccination age, situational analysis with health professionals and views of patients themselves is important to guide CC management practice.

Knowledge, attitude and practice towards cervical cancer prevention among mothers of girls aged between 9 and 14 years: a cross sectional survey in Zimbabwe.

BACKGROUND: Cervical cancer (CC) morbidity and mortality is still high in developing countries like Zimbabwe. Treatment for CC is out of reach for many women, hence the need to maximise on prevention which mainly includes screening and administering human papillomavirus (HPV) vaccine. Knowledge about CC prevention is a prerequisite for utilisation of all the available options for CC prevention, yet little is known about its levels and the corresponding attitudes and practices on cancer prevention methods within the society. METHODS: A cross sectional survey was done to assess knowledge, attitude and practice (KAP) on CC prevention among mothers of girls aged between 9 and 14 years in Zimbabwe as well as factors explaining the KAP. Four hundred and six mothers participate. Descriptive and inferential statistics (binary logistic regression and Chi-Square test of association) were applied to determine participant characteristics with KAP using STATA version 16 software. FINDINGS: Overall KAP of cervical cancer prevention is in a poor state. The knowledge was poor with 24% being able to say CC is caused by HPV; the attitude is negative with 58% being of the opinion that CC is caused by witchcraft and it is a death sentence, while the bad practices of relying only on traditional means were being practiced. Factors associated with knowledge are: not having medical aid (odds: 0.17, 95%CI: 0.05-0.59, p = 0.005) and high levels of education (secondary level odds: 4.20; 95%CI: 2.25-7.84 p < 0.001 and tertiary odds: 7.75; 95%CI: 2.04-29.45, p-value: 0.003 compared to primary education). Attitude towards CC management was driven by levels of education (secondary level odds: 0.39, 95%CI: 0.20-0.78, p = 0.007 and tertiary odds: 0.12, 95%CI: 0.04-0.33, p < 0.001), the same factor increases odds of good practice (secondary odds: 3.78, 95%CI: 1.99-7.18, p < 0.001 and tertiary odds: 3.78, 95%CI: 1.99-7.18, p < 0.001). On the other hand, HPV vaccine knowledge was also very moderate (with majority of mothers not knowing the right age of vaccination; vaccine acceptability was high (90%), but uptake was very low (8% had their daughter vaccinated). CONCLUSION: KAP about CC prevention was poor with factors necessary for improvement of KAP identified as education, medical insurance coverage. Making health education easily accessible in schools, primary health facilities and various media platforms will help to address the myths on causes of CC and how it can be treated. Health education and availability of free screening services and free vaccine will improve CC prevention out outcomes.

Mapping evidence on management of cervical cancer in sub-Saharan Africa: scoping review protocol.

BACKGROUND: Cancer is a non-communicable disease and is the number 2 leading cause of death globally. Among all cancers, cervical cancer is the number 1 killer of women in low-income countries (LICs). Cervical cancer is a well understood preventable cancer. The rates of cervical cancer are very varied and inversely proportional to the effectiveness of disease management policies. Management of cervical cancer includes prevention, screening, diagnosis and treatment. The main objective of this scoping review is to map the evidence on cervical cancer management in sub-Saharan Africa (SSA) to understand the coverage of cervical cancer prevention and treatment services and provide an opportunity to generate knowledge on the risk factors, attitudes and practices extendable globally. METHODS AND ANALYSIS: This review will be guided by Arksey and O'Malley's framework recommended for conducting scoping review studies. The Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Reviews (PRISMA-Scr) checklist will also be completed to ensure that the review adheres to the sound methodological rigour acceptable for scoping review studies. The following electronic databases will be searched for potentially eligible articles: PubMed, Ebsco Host, Scopus and Cochrane Database of Systematic Reviews. Study screening procedures recommended by Higgins and Deeks will be followed. A narrative synthesis will be used, with data synthesised and interpreted using sifting, charting and sorting based on themes and key issues. DISCUSSION: Cervical cancer can become a disease of the past with a proper control strategy in place. It is therefore imperative to map available evidence on the management of cervical cancer to inform policy and advocacy action. More knowledge on the status quo will guide policymakers in ensuring cancer management guiding policies are formulated/updated/revised accordingly. SYSTEMATIC REVIEW REGISTRATION: Not registered with PROSPERO (not needed). PROTOCOL AND REGISTRATION: This scoping review was not registered.

Pain management strategies among cervical cancer patients in Zimbabwe.

Aim: To describe pain management regulations, prevalence of pain and pain management practices in a Zimbabwean setting. Materials & methods: A multi-methods approach was used, consisting of: policy and guideline review; review of 410 cervical cancer patient records for pain symptoms and pain management data; and semistructured interviews with oncology healthcare practitioners. Results: We found a lack of policies that are specific for cervical cancer pain management. Although prevalence of pain was 68% (n = 278), only 42% of the patient records indicated pain drugs had been prescribed. Barriers to pain management included inadequate use of pain assessment tools, inaccessibility of key drugs and limited capacity. Conclusion: Cancer pain management in Zimbabwe can be improved by tailoring assessment protocols, improving drug accessibility and strengthening healthcare systems.

Lay abstract Although cancer pain has potential life-altering impact, it is not well studied in developing countries. This study aims to report on cancer pain management in Zimbabwe by reviewing policies of pain management, patient records for prevalence and assessing the practices of cancer pain management, using 410 cervical cancer patients as a model. In total, 278 (68%) cancer patients presented with pain, yet only 42% of patient records had documented prescribed pain management. We report that these findings can be consequences of restrictive policies, inadequate patient pain assessment, inaccessible pain drugs, unrecorded prescriptions and limitations of resources in the facility. Our study is important because it identifies gaps that can be addressed to improve care for cancer patients in resource-limited settings.

Working title: high dose rate intra-cavitary brachytherapy with cobalt 60 source for locally advanced cervical cancer: the Zimbabwean experience.

BACKGROUND AND PURPOSE: Cervical cancer is the fourth commonest cancer in women in the world with the highest regional incidence and mortality seen in Southern, Eastern and Western Africa. It is the commonest cause of cancer morbidity and mortality among Zimbabwean women. Most patients present with locally advanced disease that is no longer amenable to surgery. Definitive concurrent chemoradiation (CCRT), which is the use of external beam radiotherapy (EBRT) and weekly cisplatin, includes use of intracavitary brachytherapy, as the standard treatment. In the setting of this study, cobalt-60 (Co60)-based high dose rate brachytherapy (HDR-BT) has been in use since 2013. This study sought to review practices pertaining to use of brachytherapy in Zimbabwe, including timing with external beam radiotherapy, adverse effects and patient outcomes. METHODS: A retrospective analysis of data from records of patients with histologically confirmed cervical cancer treated with HDR-BT at the main radiotherapy centre in Zimbabwe from January 2013 to December 2014 was done. Outcome measures were local control, overall survival as well as gastro-intestinal and genito-urinary toxicity. RESULTS: A total of 226 patients were treated with HDR-BT during the study period, with a 97% treatment completion rate. All patients received between 45-50Gy of pelvic EBRT. Seventy-four percent received concurrent platinum-based chemotherapy. In 52% of the patients, HDR-BT was started when they were still receiving EBRT. The commonest fractionation schedule used was the 7Gy × 3 fractions, once a week (87%). Clinical complete tumour response was achieved in 75% at 6 weeks post treatment, 23% had partial response. Follow-up rates at 1 year and 2 years were 40 and 19% respectively. Disease free survival at 1 year and 2 years was 94 and 95% respectively. Vaginal stenosis was the commonest toxicity recorded, high incidence noted with increasing age. Four patients developed vesico-vaginal fistulae and two patients had rectovaginal fistulae. CONCLUSION: One hundred and seventeen patients patients started HDR-BT during EBRT course, with a treatment completion rate of 97%. The overall treatment duration was within 56 days in the majority of patients. Early local tumour control was similar for all the HDR-BT fractionation regimes used in the study, with a high rate (75%) of complete clinical response at 6 weeks post-treatment. Prospective studies to evaluate early and long-term outcomes of HDR-BT in our setting are recommended.

Clinical and demographic characteristics of cervical cancer patients presenting at Parirenyatwa Hospital, Zimbabwe.

Cervical cancer is the leading cause of cancer deaths in women in Africa, predominately due to late diagnosis. This study aims to identify risk factors, potential prognostic indicators, and optimal treatment modalities for Zimbabwean cervical cancer patients. Medical records for 1063 cervical cancer patients were reviewed for sociodemographic, clinical, treatment, and response data. All data were analysed using SPSS version 25. More than half of the cohort was pre-menopausal (63%) with low (2%) history of cervical cancer screening. Schistosoma ova were observed in 2.4% of the tumour specimens. More than 50% were diagnosed at stage 3 and later, with a high frequency of comorbidities (~68%). This study highlights a need for improving screening education and uptake in Zimbabwe. Moreover, the current data provides a dataset for understanding cervical cancer pathogenesis and treatment responses in an African cohort.

Genetic Susceptibility for Cervical Cancer in African Populations: What Are the Host Genetic Drivers?

Human papillomavirus (HPV) is an essential but not a sufficient cervical cancer etiological factor. Cancer promoters, such as host genetic mutations, significantly modulate therapeutic responses and susceptibility. In cervical cancer, of interest have been viral clearing genes and HPV oncoprotein targets, for which conflicting data have been reported among different populations. This expert analysis evaluates cervical cancer genetic susceptibility biomarkers studied in African populations. Notably, the past decade has seen Africa as a hotbed of biomarker and precision medicine innovations, thus potentially informing worldwide biomarker development strategies. We conducted a critical literature search in PubMed/MEDLINE, Google Scholar, and Scopus databases for case-control studies reporting on cervical cancer genetic polymorphisms among Africans. We found that seven African countries conducted cervical cancer molecular epidemiology studies in one of Casp8, p53, CCR2, FASL, HLA, IL10, TGF-beta, and TNF-alpha genes. This analysis reveals a remarkable gap in cervical cancer molecular epidemiology among Africans, whereas cervical cancer continues to disproportionately have an impact on African populations. Genome-wide association, whole exome- and whole-genome sequencing studies confirmed the contribution of candidate genes in cervical cancer. With such advances and omics technologies, the role of genetic susceptibility biomarkers can be exploited to develop novel interventions to improve current screening, diagnostic and prognostic methods worldwide. Exploring these genetic variations is crucial because African populations are genetically diverse and some variants or their combined effects are yet to be discovered and translated into tangible clinical applications. Thus, translational medicine and flourishing system sciences in Africa warrant further emphasis in the coming decade.

Cervical cancer in Zimbabwe: a situation analysis.

INTRODUCTION: Despite the wide-spread availability of cervical cancer prevention and screening programs in developed countries, the morbidity and mortality rates of cervical cancer in Zimbabwe are still very high. Limited resources as well as the high HIV prevalence are contributors to the high burden of cervical cancer. This paper aims to analyse the policies, frameworks and current practices in the management of cervical cancer in Zimbabwe. METHODS: A review of national documents and published literature on cervical cancer prevention, screening, treatment and knowledge in Zimbabwe was done. Informal interviews were conducted to assess the practices of cervical cancer management. RESULTS: Through strategic collaboration, a pilot for the HPV vaccination program is underway. The VIAC national cervical cancer screening program is being adopted into the current healthcare system. With regards to the treatment of precancerous lesions we found that the "see and treat" program has been implemented in colposcopy clinics. In addition, there are two multidisciplinary cancer treatment clinics installed in two central public hospitals. The general knowledge and understanding of cervical cancer is poor in Zimbabwe. CONCLUSION: Limitations in resources, infrastructure, manpower, delays in treatment and patient knowledge play a role in the high morbidity and mortality of cervical cancer in Zimbabwe. The Ministry of Health needs to increase funding to expedite the availability of HPV vaccine and screening programs. Community engagement initiatives to raise awareness on cervical cancer should be established to provide education on how to prevent the development of cervical cancer, as well as promote screening for early detection.