Partnering with traditional Chiefs to expand access to cervical cancer prevention services in rural Zambia

Objective: To evaluate how the influence of traditional Chiefs can be leveraged to promote access to cervical cancer prevention services in rural Zambia. Methods: A retrospective review of outcome data was conducted for all screening outreach events that occurred in Zambian Chiefdoms between October 4, 2015, and October 3, 2016. Members of the health promotion team of the Cervical Cancer Prevention Program in Zambia visited local Chiefs to inform them of the importance of cervical cancer prevention. The local Chiefs then summoned adults living within their Chiefdoms to assemble for cervical cancer prevention health talks. Screen-and-treat services were implemented within each of the Chiefdoms over a 1-week period. Results: VIA-enhanced digital imaging of the cervix (digital cervicography) was offered to 8399 women in ten Chiefdoms as part of a village-based screening (VBS) program. In all, 419 (4.9%) women had positive screening test results. Of these women, 276 (65.8%) were treated immediately with thermocoagulation and 143 (34.1%) were referred to provincial government hospitals to undergo either the loop electrosurgical excision procedure/large loop excision of the transformation zone (n=109, 26.0%) or punch biopsy (n=34, 8.1%). Conclusion: The influence of traditional Chiefs was leveraged to facilitate access to cervical cancer prevention services in rural Zambia

Differences in cervical cancer screening knowledge and practices by HIV status and geographic location: Implication for program implementation in Zambia

The knowledge and perceptions of cervical cancer among HIV negative and positive women, aged 25-49 years, from rural and urban locations in Zambia was systematically accessed in this study to determine any differences. Data were coded and analyzed using NVivo software. Compared to HIV negative women, HIV positive women had more accurate information about cervical cancer. They were more likely to cite male circumcision as the best approach to cervical cancer prevention. HPV infection was more commonly mentioned as a risk factor among HIV positive women. However, HIV positive women displayed little knowledge about HPV being the major cause of cervical cancer. Among HIV positive women, lack of time was the major screening barrier cited while HIV negative women mentioned being symptomatic as a determinant for early detection. Compared to rural residents, urban residents cited a wider range of cervical cancer information sources, including media and workplace although all of the participants who stated that they had no knowledge of cervical cancer were urban residents. Overall, knowledge and perceptions of cervical cancer among study participants was high, although differences exist between subgroups. Sharing accurate and standardized information on cervical cancer would improve participation in cervical cancer screening services

Minimizing Delays in the Breast Cancer Pathway by Integrating Breast Specialty Care Services at the Primary Health Care Level in Zambia

PURPOSE In Zambia, more than two-thirds of female patients with breast cancer present with late-stage disease, leading to high mortality rates. Most of the underlying causes are associated with delays in symptom recognition and diagnosis. By implementing breast care specialty services at the primary health care level, we hypothesized that some of the delays could be minimized. METHODS In March 2018, we established a breast care specialty clinic for women with symptomatic disease within 1 of the 5 district hospitals in Lusaka. The clinic offers breast self-awareness education, clinical breast examination, breast ultrasound, ultrasound-guided breast biopsy, surgery, referral for chemoradiation, follow-up care, and electronic medical records. RESULTS Between March 2018 and April 2019, of 1,790 symptomatic women who presented to the clinic, 176 (10%) had clinical and/or ultrasound indications for histologic evaluation. Biopsy specimens were obtained using ultrasound-guided core-needle procedures, all of which were performed on the same day as the initial visit. Of the 176 women who underwent biopsy, 112 (64%) had pathologic findings compatible with a primary breast cancer, and of these, 42 (37%) were early-stage (stage I/II) disease. Surgery for early-stage cancers was performed at the district hospital within 2 weeks of the time of definitive pathologic diagnosis. Patients with advanced disease were referred to the national cancer center for multimodality therapy, within a similar time frame. CONCLUSION Breast care specialty services for symptomatic women were established in a district-level hospital in a resource-constrained setting in Africa. As a result, the following time intervals were minimized: initial presentation and performance of clinical diagnostics; receipt of a definitive pathologic diagnosis and initiation of surgery; receipt of a definitive pathologic diagnosis and referral

Thermal ablation versus cryotherapy or loop excision to treat women positive for cervical precancer on visual inspection with acetic acid test: pilot phase of a randomised controlled trial

Background: Cryotherapy is standard practice for treating patients with cervical precancer in see-and-treat programmes in low-income and middle-income countries (LMICs). Because of logistical difficulties with cryotherapy (eg, the necessity, costs, and supply chain difficulties of refrigerant gas; equipment failure; and treatment duration >10 min), a battery-operated thermal ablator that is lightweight and portable has been developed. We aimed to compare thermal ablation using the new device with cryotherapy. Methods: We report the pilot phase of a randomised controlled trial in routine screen-and-treat clinics providing cervical screening using visual inspection with acetic acid (VIA) in Lusaka, Zambia. We recruited non-pregnant women, aged 25 years or older, who were eligible for ablative therapy. We randomly assigned participants (1:1:1) to thermal ablation, cryotherapy, or large loop excision of the transformation zone (LLETZ), using computer-generated allocation. The randomisation was concealed but the nurses providing treatment and the participants were unmasked. Thermal ablation was achieved using the Liger thermal ablator (using 1–5 overlapping applications of the probe heated to 100°C, each application lasting for 40 s), cryotherapy was carried out using the double-freeze technique (freeze for 3 min, thaw for 5 min, and freeze again for 3 min), and LLETZ (using a large loop driven by an electro-surgical unit to excise the transformation zone) was done under local anaesthesia. The primary endpoint was treatment success, defined as either human papillomavirus (HPV) type-specific clearance among participants who were positive for the same HPV type at baseline, or a negative VIA test at 6-month follow-up, if the baseline HPV test was negative. Per protocol analyses were done. Enrolment for the full trial is ongoing. Here, we present findings from a prespecified pilot phase of the full trial. The final analysis of the full trial will assess non-inferiority of the groups for the primary efficacy endpoint. The study is registered with ClinicalTrials.gov, number NCT02956239. Findings: Between Aug 2, 2017, and Jan 15, 2019, 750 participants were randomly assigned (250 per group). 206 (84%) participants in the cryotherapy group, 197 (81%) in the thermal ablation group, and 204 (84%) in the LLETZ group attended the 6-month follow-up examination. Treatment success was reported in 120 (60%) of 200 participants in the cryotherapy group, 123 (64%) of 192 in the thermal ablation group, and 134 (67%) of 199 in the LLETZ group (p=0·31). Few participants complained of moderate to severe pain in any group immediately after the procedure (six [2%] of 250 in the cryotherapy group, four [2%] of 250 in the thermal ablation group, and five [2%] of 250 in the LLETZ group) and 2 weeks after the procedure (one [<1%] of 241 in the cryotherapy group, none of 242 in the thermal ablation group, and two [<1%] of 237 in the LLETZ group). None of the participants reported any complication requiring medical consultation or admission to hospital. Interpretation: Results from this pilot study preliminarily suggest that thermal ablation has similar treatment success to cryotherapy, without the practical disadvantages of providing cryotherapy in an LMIC. However, the study was not powered to establish the similarity between the techniques, and results from the ongoing randomised controlled trial are need to confirm these results. Funding: US National Institutes of Health

A comprehensive assessment of breast and cervical cancer control infrastructure in Zambia

Introduction: By 2030 cancer will kill one million Africans each year. Women will bear the heaviest burden, as cancers of the breast and cervix are the most common malignancies and causes of cancer-related death in the African region. National-level data that map the status of women's cancer control services are needed to inform strategies for implementing platforms for the early detection and treatment of these “priority” cancers. Methods: Using mixed-methods, we assessed available services for breast and cervical cancer detection and treatment at all provincial hospitals, the national referral hospital, and the national cancer treatment center in Zambia. Results: A system for cervical cancer prevention using visual inspection with acetic acid (VIA) and ablation/excision of precancerous lesions has been established at the provincial level. The potential for mammography, clinical breast examination, diagnostic ultrasound and biopsy exist at the provincial level, albeit on a much smaller scale. Breast wedge resections and mastectomy can be performed in provinces where general surgeons are located; however, breast conserving and reconstructive surgery are not available. Invasive cancers are generally referred to University Teaching Hospital in Lusaka, where services for radiation, chemotherapy and hormonal therapy are available but overburdened. Pathology services nationwide are woefully inadequate. Discussion: The assessment revealed a critical need for centrally coordinated, but decentralized, public service platforms for women's cancer control. Efforts are underway, through multiple stakeholders, to implement recommendations related to training healthcare workers who can provide advanced diagnostic and therapeutic services, improving pathology services, and innovative financing for these initiatives

Demonstration of an algorithm to overcome health system-related barriers to timely diagnosis of breast diseases in rural Zambia

Background Long delays to diagnosis is a major cause of late presentation of breast diseases in sub-Saharan Africa. Aims We designed and implemented a single-visit breast care algorithm that overcomes health system-related barriers to timely diagnosis of breast diseases. Methods A multidisciplinary team of Zambian healthcare experts trained a team of mid- and high-level Zambian healthcare practitioners how to evaluate women for breast diseases, and train trainers to do likewise. Working collaboratively, the two teams then designed a clinical platform that provides multiple breast care services within a single visit. The service platform was implemented using a breast outreach camp format, during which breast self-awareness, psychosocial counseling, clinical breast examination, breast ultrasound, ultrasound-guided biopsy, imprint cytology of biopsy specimens and surgical treatment or referral, were offered within a single visit. Results Eleven hundred and twenty-nine (1129) women attended the camps for breast care. Mean age was 35.9 years. The majority were multiparous (79.4%), breast-fed (76.0%), and reported hormone use (50.4%). Abnormalities were detected on clinical breast examination in 122 (10.8%) women, 114 of whom required ultrasound. Of the 114 who underwent ultrasound, 48 had identifiable lesions and were evaluated with ultrasound-guided core needle biopsy (39) or fine-needle aspiration (9). The concordance between imprint cytology and histopathology was 100%, when breast specimens were classified as either benign or malignant. However, when specimens were classified by histopathologic subtype, the concordance between imprint cytology and histology was 85.7% for benign and 100% for malignant lesions. Six (6) women were diagnosed with invasive cancer. Eighteen (18) women with symptomatic breast lesions had next-day surgery. Significance Similar to its impact on cervical cancer prevention services, a single visit breast care algorithm has the potential to overcome health system-related barriers to timely diagnosis of breast diseases, including cancer, in rural African settings

Maternally Orphaned Children and Intergenerational Concerns Associated with Breast Cancer Deaths among Women in Sub-Saharan Africa

Importance: Low breast cancer survival in sub-Saharan Africa's young population increases the likelihood that breast cancer deaths result in maternal orphans, ie, children (<18 years) losing their mother. Objective: To estimate the number of maternal orphans and their ages for every 100 breast cancer deaths in sub-Saharan African settings during 2014-2019 and to describe family concerns about the orphaned children. Design, Setting, and Participants: Deaths occurring between September 1, 2014, and July 1, 2019, in the African Breast Cancer-Disparities in Outcomes (ABC-DO) were examined in a cohort of women diagnosed with breast cancer during 2014-2017 at major cancer treatment hospitals in Namibia, Nigeria, Uganda, and Zambia. The cohort was actively followed up for vital status via a trimonthly mobile phone call to each woman or her next of kin (typically a partner, husband, or child). Main Outcomes and Measures: The number (Poisson counts) and ages of new orphans at the time of maternal death. Results: This cohort study found that a total of 795 deaths resulted in 964 new maternal orphans, with deaths occurring in women younger than 50 years accounting for 85% of the orphans. For every 100 deaths in women younger than 50 years, there were 210 new orphans (95% CI, 196-225) overall, with country-specific estimates of 189 in Nigerian, 180 in Namibian, 222 in Ugandan, and 247 in Zambian Black women. For every 100 deaths of the women at any age, there were 121 maternal orphans, 17% of whom were younger than 5 years, 32% aged 5 to 9 years, and 51% aged 10 to 17 years at the time of maternal death. In follow-up interviews, families' concerns for children's education and childcare were reported to be exacerbated by the financial expenses associated with cancer treatment. Conclusions and Relevance: This study provides evidence that the number of maternal orphans due to breast cancer exceeds the number of breast cancer deaths among women in sub-Saharan Africa. The intergenerational consequences associated with cancer deaths in sub-Saharan Africa appear to be large and support the need for continued action to improve survival

Geospatial barriers to healthcare access for breast cancer diagnosis in sub-Saharan African settings: The African Breast Cancer—Disparities in Outcomes Cohort Study

We examined the geospatial dimension of delays to diagnosis of breast cancer in a prospective study of 1541 women newly diagnosed in the African Breast Cancer—Disparities in Outcomes (ABC-DO) Study. Women were recruited at cancer treatment facilities in Namibia, Nigeria, Uganda and Zambia. The baseline interview included information used to generate the geospatial features: urban/rural residence, travel mode to treatment facility and straight-line distances from home to first-care provider and to diagnostic/treatment facility, categorized into country/ethnicity (population)-specific quartiles. These factors were investigated in relation to delay in diagnosis (≥3 months since first symptom) and late stage at diagnosis (TNM: III, IV) using logistic regression, adjusted for population group and sociodemographic characteristics. The median (interquartile range) distances to first provider and diagnostic and treatment facilities were 5 (1-37), 17 (3-105) and 62 (5-289) km, respectively. The majority had a delay in diagnosis (74%) and diagnosis at late stage (64%). Distance to first provider was not associated with delay in diagnosis or late stage at diagnosis. Rural residence was associated with delay, but the association did not persist after adjustment for sociodemographic characteristics. Distance to the diagnostic/treatment facility was associated with delay (highest vs lowest quartile: odds ratio (OR) = 1.56, 95% confidence interval (CI) = 1.08-2.27) and late stage (overall: OR = 1.47, CI = 1.05-2.06; without Nigerian hospitals where mostly local residents were treated: OR = 1.73, CI = 1.18-2.54). These findings underscore the need for measures addressing the geospatial barriers to early diagnosis in sub-Saharan African settings, including providing transport or travel allowance and decentralizing diagnostic services

Breast cancer survival and survival gap apportionment in sub-Saharan Africa (ABC-DO): a prospective cohort study

Background: Breast cancer is the second leading cause of death from cancer in women in sub-Saharan Africa, yet there are few well characterised large-scale survival studies with complete follow-up data. We aimed to provide robust survival estimates in women in this setting and apportion the survival gaps. Methods: The African Breast Cancer-Disparities in Outcomes (ABC-DO) prospective cohort study was done at eight hospitals across five sub-Saharan African countries (Namibia, Nigeria, South Africa, Uganda, and Zambia). We prospectively recruited women (aged ≥18 years) who attended these hospitals with suspected breast cancer. Women were actively followed up by use of a telephone call once every 3 months, and a mobile health application was used to keep a dynamic record of follow-up calls due. We collected detailed sociodemographic, clinical, and treatment data. The primary outcome was 3-year overall survival, analysed by use of flexible proportional mortality models, and we predicted survival under scenarios of modified distributions of risk factors. Findings: Between Sept 8, 2014, and Dec 31, 2017, 2313 women were recruited from these eight hospitals, of whom 85 did not have breast cancer. Of the remaining 2228 women with breast cancer, 58 women with previous treatment or recurrence, and 14 women from small racial groups (white and Asian women in South Africa), were excluded. Of the 2156 women analysed, 1840 (85%) were histologically confirmed, 129 (6%) were cytologically confirmed, and 187 (9%) were clinically confirmed to have breast cancer. 2156 (97%) women were followed up for up to 3 years or up to Jan 1, 2019, whichever was earlier. Up to this date, 879 (41%) of these women had died, 1118 (52%) were alive, and 159 (7%) were censored early. 3-year overall survival was 50% (95% CI 48–53), but we observed variations in 3-year survival between different races in Namibia (from 90% in white women to 56% in Black women) and in South Africa (from 76% in mixed-race women to 59% in Black women), and between different countries (44–47% in Uganda and Zambia vs 36% in Nigeria). 215 (10%) of all women had died within 6 months of diagnosis, but 3-year overall survival remained low in women who survived to this timepoint (58%). Among survival determinants, improvements in early diagnosis and treatment were predicted to contribute to the largest increases in survival, with a combined absolute increase in survival of up to 22% in Nigeria, Zambia, and Uganda, when compared with the contributions of other factors (such as HIV or aggressive subtypes). Interpretation: Large variations in breast cancer survival in sub-Saharan African countries indicate that improvements are possible. At least a third of the projected 416 000 breast cancer deaths that will occur in this region in the next decade could be prevented through achievable downstaging and improvements in treatment. Improving survival in socially disadvantaged women warrants special attention. Funding: Susan G Komen and the International Agency for Research on Cancer

Few Losses to Follow-up in a Sub-Saharan African Cancer Cohort via Active Mobile Health Follow-up

Accurate survival estimates are needed for guiding cancer control efforts in sub-Saharan Africa, but previous studies have been hampered by unknown biases due to excessive loss to follow-up (LTFU). In the African Breast Cancer-Disparities in Outcomes Study, a prospective breast cancer cohort study, we implemented active mobile health follow-up, telephoning each woman or her next-of-kin (NOK) trimonthly on her mobile phone to update information on her vital status. Dates of every contact with women/NOK were analyzed from diagnosis in 2014-2017 to the earliest of September 1, 2018, death, or 3 years postdiagnosis. The cumulative incidence of being LTFU was calculated considering deaths as competing events. In all, 1,490 women were followed for a median of 24.2 (interquartile range (IQR), 14.2-34.5) months, corresponding to 8,529 successful contacts (77% of total contacts) with the women/NOK. Median time between successful contacts was 3.0 (IQR, 3.0-3.7) months. In all, 71 women (5.3%) were LTFU at 3 years: 0.8% in Nigeria, 2.2% in Namibia, and 5.6% in Uganda. Because of temporary discontinuity of active follow-up, 20.3% of women were LTFU after 2 years in Zambia. The median time to study notification of a death was 9.1 (IQR, 3.9-14.0) weeks. Although the present study was not a randomized controlled trial, in this cancer cohort with active mobile health follow-up, LTFU was much lower than in previous studies and enabled estimation of up-to-date and reliable cancer survival