Reproductive history and breast cancer survival: Findings from the African breast cancer-Disparities in outcomes cohort and implications of Africa's fertility transition on breast cancer prognosis.

Reproductive characteristics are known risk factors for breast cancer but, other than recent birth, their role as prognostic factors is less clear, and has not been studied in Sub-Saharan Africa (SSA). In this setting, we examined whether reproductive factors independently influence breast cancer survival in a subset of the African Breast Cancer-Disparities in Outcomes cohort study. In 1485 women with incident breast cancer recruited between 2014 and 2017, we examined birth cohort changes in reproductive factors, and used Cox models to examine whether reproductive characteristics were associated with all-cause mortality after adjusting for confounders (age, stage, treatment, HIV, and social factors). Four years after diagnosis, 822 (56%) women had died. Median parity was 4 (IQR = 2, 6) and 209 (28%) of premenopausal women had had a recent birth (<3 years prior to cancer diagnosis). Each pregnancy was associated with a 5% increase (95% CI: 2%, 8%) in mortality rates, which held among postmenopausal women (5%, [1%-9%]). Pre-menopausal women with a recent birth had 52% (20%, 92%) higher mortality rates. Fertility trends by birth cohort showed declining parity, increasing age at first birth and declining age at last birth, however the impact of these population-level changes on future average survival was predicted to be very small (<3% absolute gain).

Treatment guideline concordance, initiation, and abandonment in patients with non-metastatic breast cancer from the African Breast Cancer-Disparities in Outcomes (ABC-DO) cohort in sub-Saharan Africa: a prospective cohort study.

BACKGROUND: Comprehensive breast cancer management is essential to achieve high breast cancer survival; however, detailed reports of the treatment regimens received by patients are scarce in sub-Saharan Africa where survival is low. We aimed to examine treatment initiation, guideline concordance, and abandonment in patients with non-metastatic breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes (ABC-DO) prospective cohort. METHODS: The ABC-DO prospective cohort study recruited women (aged ≥18 years) with newly diagnosed invasive breast cancer in eight hospitals across five sub-Saharan African countries (Namibia, Nigeria, Uganda, South Africa, and Zambia). We analysed treatments received by women who were classified as non-metastatic (M0) at the initial presentation. Data on surgery, radiotherapy, and systemic therapies were obtained from medical records and a self-reported follow-up questionnaire at 6 months after the diagnosis, follow-up calls every 3 months, and a baseline questionnaire. Initiation, completion, and abandonment of treatment modalities and combined therapy regimens were examined overall, by country-specific groups, and by clinical factors relevant for guideline-based treatment. FINDINGS: Of 2313 women recruited into the ABC-DO study between Sept 10, 2014, and Dec 31, 2017, 2226 had histologically or clinically confirmed breast cancer. Of these 2226 women, 510 were excluded from the present analysis because 378 had metastatic disease, 37 were prevalent cases (defined as those previously diagnosed with breast cancer >2 years before baseline), 82 had unknown TNM stage, and 13 were White or Asian women in South Africa (number was too small for analysis). After a median follow-up of 5·2 years (IQR 4·6-5·9), 1163 (68%) of 1716 women underwent breast cancer surgery. Surgery and systemic therapy (ie, multimodality treatment) with radiotherapy was initiated in 370 (36%) of 1028 women with localised tumours versus 156 (23%) of 688 women with locally advanced tumours, whereas multimodality treatment without radiotherapy was initiated in 386 (38%) versus 167 (24%) women, respectively. Of 1530 patients requiring chemotherapy (which excludes 105 who died within 6 months after baseline), 1013 (66%) initiated treatment of neoadjuvant chemotherapy or surgery within 3 months after baseline, which was adequately completed by 359 (35%) of 1013 women, marginally completed by 284 (28%), abandoned by 200 (20%), and unknown in 151 (15%). 19 (2%) women died within 6 months after chemotherapy initiation. Of 1375 women in whom endocrine therapy was indicated, this treatment was initiated in 920, and lasted at least 3 years in 367 (40%) women. Treatment disparities between country-specific groups were substantial for all therapy regimens. INTERPRETATION: A high proportion of patients with non-metastatic breast cancer did not initiate, did not fully complete, or abandoned treatment with surgery, systemic therapy, radiotherapy, or an appropriate combination of these, highlighting the need for improved treatment access and completion in sub-Saharan Africa to potentially prevent premature breast cancer deaths. FUNDING: National Institutes of Health (National Cancer Institute), Susan G Komen, and the International Agency for Research on Cancer.

Inequities in Adverse Maternal and Perinatal Outcomes: The Effect of Maternal Race and Nativity.

OBJECTIVES: To evaluate the effect of race and ethnicity on differences in maternal and perinatal outcomes among U.S.-born and foreign-born women, as well as racial and ethnic disparities in outcomes within these groups. METHODS: This retrospective study analyzed singleton pregnancies (n = 11,518) among women delivering at Boston Medical Center from January 2010-March 2015. Outcomes of interest included preterm birth, early preterm birth, cesarean delivery, hypertensive disorders, diabetes, low birth weight at term (LBW, < 2500 g), NICU admission and intrauterine fetal demise (IUFD). Prevalence ratios and 95% confidence intervals comparing outcomes between U.S.- and foreign-born women were calculated and stratified by race. Obstetric outcomes among Black and Hispanic women were compared to those of white women within both U.S.- and foreign-born groups. RESULTS: Preterm birth, hypertensive disorders, LBW and NICU admission were more likely to occur among U.S.-born women and their neonates compared to foreign-born women. Controlling for sociodemographic characteristics did not significantly impact these disparities. Among foreign-born women, Black women had a higher prevalence of many maternal and neonatal complications, while Hispanic women had a lower prevalence of some complications compared to white women. Black woman and infants consistently exhibit worse outcomes regardless of their nativity, while Hispanic women foreign-born women experience less disparate outcomes. CONCLUSIONS FOR PRACTICE: Overall, women born in the United States are at higher risk of several adverse perinatal outcomes compared to foreign-born women. Racial and ethnic disparities in birth outcomes exist in both groups. However, the complex interplay between biopsychosocial influences that mediate these inequities appear to have different effects among U.S- and foreign- born women. A better understanding of these factors can be used to combat disparities and improve outcomes for all women.

Cervical cancer screening, abnormal results, and follow-up in women with substance use-related diagnoses.

Background: Substance use-related diagnoses are common and associated with poor health outcomes. The objective of this analysis was to compare rates of cervical cancer screening, screening abnormalities, and follow-up care in women with and without a substance use-related diagnosis seen for primary care between January 1, 2016 and December 31, 2019 in the University of Washington healthcare system. Methods: This study included women aged 21-65 years of age who had at least one outpatient visit between January 1, 2016 and December 31, 2019 within one of 45 primary care or women's health clinics in the academic healthcare system. Exposure status was defined using ICD10 codes for substance-use related diagnoses or no substance-use related diagnoses. Only first cervical cancer screening was included. Generalized linear models with a binomial family and log link were used to estimate risk ratios. Results: 3845 women had a substance use-related diagnosis and 89214 did not. Women with a substance use-related diagnosis were less likely to be screened for cervical cancer (44%, 1675/3845) compared to women without a substance use-related diagnosis (49%, 43338/89214; relative risk [RR] 0.90, 95% CI 0.86-0.93). Women with a substance use-related diagnosis were also more likely to have an abnormal screening result (18%, 304/1675) compared to women without a substance use-related diagnosis (10%, 4528/43338; RR 1.74, 95% CI 1.56-1.93). Follow-up for abnormal screens did not differ significantly between groups (24 vs 25%; RR 0.80, 95% CI 0.55-1.17). Conclusion: To combat disparities in cervical cancer screening for women with substance use-related diagnoses, public health efforts should expand access to screening where women with substance use-related diagnoses are seen, including acute care, inpatient hospitalizations, and addiction treatment settings.

Self-reported arm and shoulder problems in breast cancer survivors in Sub-Saharan Africa: the African Breast Cancer-Disparities in Outcomes cohort study.

BACKGROUND: Arm and shoulder problems (ASP), including lymphedema, were common among women with breast cancer in high-income countries before sentinel lymph node biopsy became the standard of care. Although ASP impair quality of life, as they affect daily life activities, their frequency and determinants in Sub-Saharan Africa remain unclear. METHODS: All women newly diagnosed with breast cancer at the Namibian, Ugandan, Nigerian, and Zambian sites of the African Breast Cancer-Disparities in Outcomes (ABC-DO) cohort study were included. At each 3-month follow-up interview, women answered the EORTC-QLQ-Br23 questionnaire, including three ASP items: shoulder/arm pain, arm stiffness, and arm/hand swelling. We estimated the cumulative incidence of first self-reported ASP, overall and stratified by study and treatment status, with deaths treated as competing events. To identify determinants of ASP, we estimated cause-specific hazard ratios using Cox models stratified by study site. RESULTS: Among 1476 women, up to 4 years after diagnosis, 43% (95% CI 40-46), 36% (33-38) and 23% (20-25), respectively, self-reported having experienced arm/shoulder pain, stiffness and arm/hand swelling at least once. Although risks of self-reported ASP differed between sites, a more advanced breast cancer stage at diagnosis, having a lower socioeconomic position and receiving treatment increased the risk of reporting an ASP. CONCLUSION: ASP are very common in breast cancer survivors in Sub-Saharan Africa. They are influenced by different factors than those observed in high-income countries. There is a need to raise awareness and improve management of ASP within the African setting.

Dissecting the journey to breast cancer diagnosis in sub-Saharan Africa: Findings from the multicountry ABC-DO cohort study.

Most breast cancer patients in sub-Saharan Africa are diagnosed at advanced stages after prolonged symptomatic periods. In the multicountry African Breast Cancer-Disparities in Outcomes cohort, we dissected the diagnostic journey to inform downstaging interventions. At hospital presentation for breast cancer, women recalled their diagnostic journey, including dates of first noticing symptoms and health-care provider (HCP) visits. Negative binomial regression models were used to identify correlates of the length of the diagnostic journey. Among 1429 women, the median (inter-quartile range) length (months) of the diagnostic journey ranged from 11.3 (5.7-21.2) in Ugandan, 8.2 (3.4-16.4) in Zambian, 6.5 (2.4-15.7) in Namibian-black to 5.6 (2.3-13.1) in Nigerian and 2.4 (0.6-5.5) in Namibian-non-black women. Time from first HCP contact to diagnosis represented, on average, 58% to 79% of the diagnostic journey in each setting except Nigeria where most women presented directly to the diagnostic hospital with advanced disease. The median number of HCPs visited was 1 to 4 per woman, but time intervals between visits were long. Women who attributed their initial symptoms to cancer had a 4.1 months (absolute) reduced diagnostic journey than those who did not, while less-educated (none/primary) women had a 3.6 months longer journey than more educated women. In most settings the long journey to breast cancer diagnosis was not primarily due to late first presentation but to prolonged delays after first presentation to diagnosis. Promotion of breast cancer awareness and implementation of accelerated referral pathways for women with suspicious symptoms are vital to downstaging the disease in the region.

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.

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.

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.

Drivers of advanced stage at breast cancer diagnosis in the multicountry African breast cancer - disparities in outcomes (ABC-DO) study.

Breast cancer (BC) survival rates in sub-Saharan Africa (SSA) are low in part due to advanced stage at diagnosis. As one component of a study of the entire journey of SSA women with BC, we aimed to identify shared and setting-specific drivers of advanced stage BC. Women newly diagnosed in the multicountry African Breast Cancer-Disparities in Outcomes (ABC-DO) study completed a baseline interview and their stage information was extracted from medical records. Ordinal logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for advanced stage (I, II, III, IV) in relation to individual woman-level, referral and biological factors. A total of 1795 women were included from Nigeria, Uganda, Zambia, and the multiracial populations of Namibia and South Africa, 1091 of whom (61%) were stage III/IV. Stage was lower in women with greater BC knowledge (OR 0.77 (95% CI: 0.70, 0.85) per point on a 6 point scale). More advanced stage was associated with being black (4.00 (2.79, 5.74)), having attended

Breast cancer awareness in the sub-Saharan African ABC-DO cohort: African Breast Cancer-Disparities in Outcomes study.

A greater understanding of the nature and drivers of poor breast cancer (BC) awareness in sub-Saharan Africa (SSA) will inform much needed awareness programmes. We aimed to assess the level and nature of BC awareness in the multi-country African Breast Cancer-Disparities in Outcome (ABC-DO) cohort of women newly diagnosed with BC during 2014-2017. Awareness indicators were assessed during a baseline interview at/near diagnosis. Logistic/ordinal regression was used to estimate odds ratios (OR) for indicators of BC awareness in relation to woman-level characteristics for individual settings and then meta-analyzed. In the 1,451 women included, almost all Namibian non-black women (n = 104) knew of BC and its curability, while in Namibian black and Zambian women, one in 7 (~ 15%) had not previously heard of BC and 25-40% did not know it was curable. In Uganda and Nigeria awareness was lowest: one in four women had no BC awareness, and 2 in 3 had no knowledge of its cure potential. Low educational level, unskilled employment, low socioeconomic position, rural residence, older age, being unmarried, and in some settings HIV-positivity, were associated with lower BC awareness-e.g., having unskilled employment was associated with not having heard of BC (summary OR 3.37; 95% confidence interval (CI) 2.17-5.23), believing that it is incurable (2.43; 1.81-3.26), and not recognizing a breast lump symptom (1.85; 1.41-2.43) but with between-setting variation (I2 > 68% for all). The findings provide evidence of the level and difference in BC awareness and beliefs across different settings, highlighting the urgent need for context-specific education programmes in the SSA region.

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.

Nurse-midwives' ability to diagnose acute third- and fourth-degree obstetric lacerations in western Kenya.

BACKGROUND: Obstetric fistula devastates the lives of women and is found most commonly among the poor in resource-limited settings. Unrepaired third- and fourth-degree perineal lacerations have been shown to be the source of approximately one-third of the fistula burden in fistula camps in Kenya. In this study, we assessed potential barriers to accurate identification by Kenyan nurse-midwives of these complex perineal lacerations in postpartum women. METHODS: Nurse-midwife trainers from each of the seven sub-counties of Siaya County, Kenya were assessed in their ability to accurately identify obstetric lacerations and anatomical structures of the perineum, using a pictorial assessment tool. Referral pathways, follow-up mechanisms, and barriers to assessing obstetric lacerations were evaluated. RESULTS: Twenty-two nurse-midwife trainers were assessed. Four of the 22 (18.2%) reported ever receiving formal training on evaluating third- and fourth-degree obstetric lacerations, and 20 of 22 (91%) reported health-system challenges to adequately completing their examination of the perineum at delivery. Twenty-one percent of third- and fourth-degree obstetric lacerations in the pictorial assessment were incorrectly identified as first- or second-degree lacerations. CONCLUSION: County nurse-midwife trainers in Siaya, Kenya, experience inadequate training, equipment, staffing, time, and knowledge as barriers to adequate diagnosis and repair of third- and fourth-degree perineal tears.

Reduced-Dose HPV Vaccination - Implications for Cancer Prevention Policy.

Human papillomaviruses (HPVs), of which there are over 200 types, typically infect cells of the skin and mucosa. Most infections are cleared by the immune system without any intervention; however, in a small percentage of infected individuals, the virus persists, resulting in a variety of disorders. More specifically, 13 HPV types have been characterized as oncogenic because of their central role in the development of premalignant and malignant lesions of the oropharynx (mouth and throat), lower gastrointestinal tract (anus), and genital organs (uterine cervix, vagina, vulva, and penis). Worldwide, HPV infections contribute to approximately 5% of all cancers, with an estimated 625,000 women and 69,000 men affected annually by HPV-related cancers.

A portable thermal ablation device for cervical cancer prevention in a screen-and-treat setting: a randomized, noninferiority trial.

Implementing standard-of-care cryotherapy or electrosurgical excision to treat cervical precancers is challenging in resource-limited settings. An affordable technological alternative that is as effective as standard-of-care techniques would greatly improve access to treatment. This randomized controlled trial aims to demonstrate the noninferiority efficacy of a portable, battery-driven thermal ablation (TA) device compared to cryotherapy and electrosurgical excision (large loop excision of transformation zone (LLETZ)) to treat cervical precancer in a screen-and-treat program in Zambia. A total of 3,124 women positive on visual inspection with acetic acid and eligible for ablative therapy were randomized to one of the treatment arms. Human papillomavirus (HPV) testing was performed at baseline and at the follow-up. The primary outcome was treatment success, defined as either type-specific HPV clearance at the follow-up in participants positive for HPV at baseline, or a negative visual inspection with acetic acid test for those who had a negative HPV test at baseline. After a median follow-up of 12 months, treatment success rates were 74.0%, 71.1% and 71.4% for the TA, cryotherapy and LLETZ arms, respectively, thus demonstrating noninferiority (P = 0.83). TA was a safe and well-accepted procedure. Only 3.6% of those randomized to TA reported moderate-to-severe pain, compared to 6.5% and 1.9% for the cryotherapy and LLETZ arms, respectively. Thus, our randomized controlled trial demonstrates the safety and efficacy of TA, which is not inferior to cryotherapy or surgical excision.ClinicalTrials.gov registration: NCT02956239 .

Geospatial disparities in survival of patients with breast cancer in sub-Saharan Africa from the African Breast Cancer-Disparities in Outcomes cohort (ABC-DO): a prospective cohort study.

BACKGROUND: There is an urgent need to improve breast cancer survival in sub-Saharan Africa. Geospatial barriers delay diagnosis and treatment, but their effect on survival in these settings is not well understood. We examined geospatial disparities in 4-year survival in the African Breast Cancer-Disparities in Outcomes cohort. METHODS: In this prospective cohort study, women (aged ≥18 years) newly diagnosed with breast cancer were recruited from eight hospitals in Namibia, Nigeria, South Africa, Uganda, and Zambia. They reported sociodemographic information in interviewer-administered questionnaires, and their clinical and treatment data were collected from medical records. Vital status was ascertained by contacting participants or their next of kin every 3 months. The primary outcome was all-cause mortality in relation to rural versus urban residence, straight-line distance, and modelled travel time to hospital, analysed using restricted mean survival time, Cox proportional hazards, and flexible parametric survival models. FINDINGS: 2228 women with breast cancer were recruited between Sept 8, 2014, and Dec 31, 2017. 127 were excluded from analysis (58 had potentially recurrent cancer, had previously received treatment, or had no follow-up; 14 from minority ethnic groups with small sample sizes; and 55 with missing geocoded home addresses). Among the 2101 women included in analysis, 928 (44%) lived in a rural area. 1042 patients had died within 4 years of diagnosis; 4-year survival was 39% (95% CI 36-42) in women in rural areas versus 49% (46-52) in urban areas (unadjusted hazard ratio [HR] 1·24 [95% CI 1·09-1·40]). Among the 734 women living more than 1 h from the hospital, the crude 4-year survival was 37% (95% CI 32-42) in women in rural areas versus 54% (46-62) in women in urban areas (HR 1·35 [95% CI 1·07-1·71] after adjustment for age, stage, and treatment status). Among women in rural areas, mortality rates increased with distance (adjusted HR per 50 km 1·04, 1·01-1·07) and travel time (adjusted HR per h 1·06, 1·02-1·10). Among women with early-stage breast cancer receiving treatment, women in rural areas had a strong survival disadvantage (overall HR 1·54, 1·14-2·07 adjusted for age and stage; >1 h distance adjusted HR 2·14, 1·21-3·78). INTERPRETATION: Geospatial barriers reduce survival of patients with breast cancer in sub-Saharan Africa. Specific attention is needed to support patients with early-stage breast cancer living in rural areas far from cancer treatment facilities. FUNDING: US National Institutes of Health (National Cancer Institute), Susan G Komen for the Cure, and the International Agency for Research on Cancer.

Implementation and scale-up of a single-visit, screen-and-treat approach with thermal ablation for sustainable cervical cancer prevention services: a protocol for a stepped-wedge cluster randomized trial in Kenya.

BACKGROUND: An important cervical cancer prevention strategy in low- and middle-income countries (LMICs) has been single-visit screen-and-treat (SV-SAT) approach, using visual inspection with acetic acid (VIA) and ablative treatment with cryotherapy to manage precancerous lesions. While SV-SAT with VIA and cryotherapy have established efficacy, its population level coverage and impact on reducing cervical cancer burden remains low. In Kenya, the estimated cervical cancer screening uptake among women aged 30-49 is 16% and up to 70% of screen-positive women do not receive treatment. Thermal ablation for treatment of precancerous lesions of the cervix is recommended by the World Health Organization and has the potential to overcome logistical challenges associated with cryotherapy and facilitate implementation of SV-SAT approach and increase treatment rates of screen-positive women. In this 5-year prospective, stepped-wedge randomized trial, we plan to implement and evaluate the SV-SAT approach using VIA and thermal ablation in ten reproductive health clinics in central Kenya. METHODS: The study aims to develop and evaluate implementation strategies to inform the national scale-up of SV-SAT approach with VIA and thermal ablation through three aims: (1) develop locally tailored implementation strategies using multi-level participatory method with key stakeholders (patient, provider, system-level), (2) implement SV-SAT approach with VIA and thermal ablation and evaluate clinical and implementation outcomes, and (3) assess the budget impact of SV-SAT approach with VIA and thermal ablation compared to single-visit, screen-and-treat method using cryotherapy. DISCUSSION: Our findings will inform national scale-up of the SV-SAT approach with VIA and thermal ablation. We anticipate that this intervention, along with tailored implementation strategies will enhance the adoption and sustainability of cervical cancer screening and treatment compared to the standard of care using cryotherapy. TRIAL REGISTRATION: NCT05472311.

Gynaecologic oncology surgical cancellations in Zambia.

Introduction: Cancellations of elective surgery in low-and middle-income countries (LMIC) are common and a major hindrance for patients who are in need of surgical therapeutic modalities. This is especially important in the context of scaling up needed surgical interventions for gynaecological cancer care. There is a knowledge gap in the literature related to cancellation of gynaecologic oncology surgeries in LMIC, where there is enormous need for this specific cancer surgical capacity. We report in an observational descriptive fashion, our experience at the UTH/CDH in Lusaka, Zambia, on the causes of surgical cancellations in gynaecologic oncology. Methods: From January 1, 2021 through June 31, 2023, we retrospectively evaluated the surgical registry for gynaecologic oncology at the UTH/CDH in Lusaka, Zambia to assess the number and causes of surgical cancellations. Results: There were a total of 66 (16.96%) surgical cancellations out of 389 scheduled gynaecologic oncology cases. Lack of available blood and/or low haemoglobin was the most frequent cause of surgical cancellations, 27 cases (40.90%). Conclusion: We highlight in our series that the lack of blood, leading to surgical cancellations was the most frequent impediment related to performing scheduled gynaecologic oncology surgical procedures. As gynaecologic oncology services scale up in LMIC, given the radical nature of surgery and its association with blood loss, it is incumbent on the entire clinical ecosystem to address this issue and to develop mitigating strategies, specific to their respective resource setting.

Durability of single-dose HPV vaccination in young Kenyan women: randomized controlled trial 3-year results.

Cervical cancer burden is high where prophylactic vaccination and screening coverage are low. We demonstrated in a multicenter randomized, double-blind, controlled trial that single-dose human papillomavirus (HPV) vaccination had high vaccine efficacy (VE) against persistent infection at 18 months in Kenyan women. Here, we report findings of this trial through 3 years of follow-up. Overall, 2,275 healthy women aged 15-20 years were recruited and randomly assigned to receive bivalent (n = 760), nonavalent (n = 758) or control (n = 757) vaccine. The primary outcome was incident-persistent vaccine type-specific cervical HPV infection. The primary evaluation was superiority analysis in the modified intention-to-treat (mITT) HPV 16/18 and HPV 16/18/31/33/45/52/58 cohorts. The trial met its prespecified end points of vaccine type-specific persistent HPV infection. A total of 75 incident-persistent infections were detected in the HPV 16/18 mITT cohort: 2 in the bivalent group, 1 in the nonavalent group and 72 in the control group. Nonavalent VE was 98.8% (95% CI 91.3-99.8%, P < 0.0001) and bivalent VE was 97.5% (95% CI 90.0-99.4%, P < 0.0001). Overall, 89 persistent infections were detected in the HPV 16/18/31/33/45/52/58 mITT cohort: 5 in the nonavalent group and 84 in the control group; nonavalent VE was 95.5% (95% CI 89.0-98.2%, P < 0.0001). There were no vaccine-related severe adverse events. Three years after vaccination, single-dose HPV vaccination was highly efficacious, safe and conferred durable protection. ClinicalTrials.gov no. NCT03675256 .

High-risk human papillomavirus-associated vulvar neoplasia among women living with human immunodeficiency virus in Zambia.

Background: Globally, women living with HIV have a higher risk of vulvar neoplasia than HIV-negative women. Vulvar neoplasia among women living with HIV has not previously been characterised in Zambia. Objective: This study determined the clinical and pathologic features of vulvar neoplasia among women living with HIV at the University Teaching Hospital, Lusaka, Zambia. Methods: We conducted a cross-sectional study of vulvar lesions among 53 women living with HIV who presented with vulvar lesions between July 2017 and February 2018. The study assessed clinical and histological characteristics and prevalence of high-risk human papillomavirus (HRHPV). Results: Twenty-one patients were diagnosed with vulvar squamous cell carcinoma (VSCC), 20 with usual vulvar intraepithelial neoplasm (uVIN), and the rest with either benign lesions or non-neoplastic lesions (NNL). Participants' mean age was 40 years. Patients with VSCC were significantly older than those with NNL (mean (s.d.): 43 (21) vs 33 (10), p = 0.004). The prevalence of HRHPV was 88.9% in VSCC patients and 100.0% in high-grade squamous intraepithelial lesion patients. HPV16 was the most common (52.6%) genotype. The clinical features of neoplasia were similar to those of NNL. Conclusion: VSCC was significantly more common among women aged ≥ 40 years. HRHPV in VSCC and high-grade squamous intraepithelial lesions was high. Women with vulvar lesions, especially those aged > 40 years, should be evaluated for vulvar cancer. Young girls should be vaccinated to prevent vulvar cancer.