State of the Science of Scale-Up of Cancer Prevention and Early Detection Interventions in Low- and Middle-Income Countries: A Scoping Review.

PURPOSE: Cancer deaths in low- and middle-income countries (LMICs) will nearly double by 2040. Available evidence-based interventions (EBIs) for cancer prevention and early detection can reduce cancer-related mortality, yet there is a lack of evidence on effectively scaling these EBIs in LMIC settings. METHODS: We conducted a scoping review to identify published literature from six databases between 2012 and 2022 that described efforts for scaling cancer prevention and early detection EBIs in LMICs. Included studies met one of two definitions of scale-up: (1) deliberate efforts to increase the impact of effective intervention to benefit more people or (2) an intervention shown to be efficacious on a small scale expanded under real-world conditions to reach a greater proportion of eligible population. Study characteristics, including EBIs, implementation strategies, and outcomes used, were summarized using frameworks from the field of implementation science. RESULTS: This search yielded 3,076 abstracts, with 24 studies eligible for inclusion. Included studies focused on a number of cancer sites including cervical (67%), breast (13%), breast and cervical (13%), liver (4%), and colon (4%). Commonly reported scale-up strategies included developing stakeholder inter-relationships, training and education, and changing infrastructure. Barriers to scale-up were reported at individual, health facility, and community levels. Few studies reported applying conceptual frameworks to guide strategy selection and evaluation. CONCLUSION: Although there were relatively few published reports, this scoping review offers insight into the approaches used by LMICs to scale up cancer EBIs, including common strategies and barriers. More importantly, it illustrates the urgent need to fill gaps in research to guide best practices for bringing the implementation of cancer EBIs to scale in LMICs.

Cascade Analysis for Women Presenting With Breast Concerns to a Zonal Hospital in Mwanza, Tanzania.

PURPOSE: In Tanzania, high breast cancer mortality can be attributed to delays in diagnosis and treatment initiation. We adapted the cascade analysis method to depict sequential steps along the breast cancer care pathway in a tertiary hospital in Mwanza, to identify where correction of loss to attrition would have the biggest impact on improving outcomes. METHODS: This prospective cohort included adult women presenting with breast concerns between February 2020 and January 2022. Five cascade steps beginning with patients' initial clinical breast assessment (CBA) through cancer treatment were identified: (1) CBA, (2) ordering diagnostic test(s), (3) completion of diagnostic test(s), (4) receipt of final diagnosis, and (5) initiating cancer treatment. RESULTS: Overall, 721 eligible women with a median age of 42.8 years (IQR, 32.5-55.0) were included. Median time from presentation to treatment initiation was 35 days (IQR, 20-63). For step 1, 39.1% (n = 282) of patients were diagnosed with a benign concern and removed from the cascade. Completion rates for steps 2-4 were 95.0%, 90.2%, and 91.0, respectively. There were 156 (45.6%) patients diagnosed with breast cancer, and for step 5, 71.2% of patients initiated cancer treatment. In steps 2, 3, 4, and 5, there was a loss of 22, 41, 34, and 45 patients, respectively. If loss was eliminated at steps 2, 3, 4, or 5, an additional 6, 12, 11, or 45 patients, respectively, would have completed the pathway. CONCLUSION: Initiating cancer treatment was identified as the step with the biggest loss and, if remedied, would have the biggest impact on improving breast cancer outcomes at Bugando Medical Centre. These results will inform future programs focused on reducing overall loss in the system and supporting patients with breast cancer.

Cervical cancer screening in HIV-endemic countries: An urgent call for guideline change.

Women living with HIV (WLWH) are at an increased risk of developing HPV-related high grade cervical dysplasia and cervical cancer. Prior World Health Organization (WHO) screening guidelines recommended starting screening at age 30. We assessed characteristics of women diagnosed with cervical cancer to further inform and refine screening guidelines. We prospectively enrolled women diagnosed with cervical cancer from January 2015 to March 2020 at two tertiary hospitals in Gaborone, Botswana. We performed chi-square and ANOVA analyses to evaluate the association between age upon diagnosis and HIV status, CD4 count, viral load, and other sociodemographic and clinical factors. Data were available for 1130 women who were diagnosed with cervical cancer and 69.3% were WLWH. The median age overall was 47.9 (IQR 41.2-59.1), 44.6 IQR: 39.8 - 50.9) among WLWH, and 61.2 (IQR 48.6-69.3) among women living without HIV. There were 1.3% of women aged <30 years old, 19.1% were 30-39 and 37.2% were 40-49. Overall, 20.4% (n = 231) of cancers were in women <40 years. Age of cervical cancer diagnosis is younger in countries with higher HIV prevalence, like Botswana. Approximately 20% of the patients presented with cancer at <40 years of age and would have likely benefited from screening 10 years prior to cancer diagnosis to provide an opportunity for detection and treatment of pre-invasive disease.

Distance to Multidisciplinary Team Clinic in Gaborone, Botswana, and Stage at Cervical Cancer Presentation for Women Living With and Without HIV.

PURPOSE: Cervical cancer is the leading cause of cancer death for women in Botswana. Barriers in access to cancer care can lead to later stages at diagnosis and increased mortality. This study evaluated access, defined as travel time from a patient's residential village to a multidisciplinary team clinic in Gaborone, with stage of cervical cancer at presentation. In addition, because of the high HIV prevalence in Botswana, we explored the association between travel time and HIV status. METHODS: Eligible patients with cervical cancer presenting to the multidisciplinary team between 2015 and 2020 were included. Data were abstracted from questionnaires and hospital records. Google Maps was used to calculate travel time. Multinomial regression was used to examine travel time and cancer stage, and multivariable logistic regression was used to investigate travel time and HIV status. RESULTS: We identified 959 patients with cervical cancer of which 70.1% were women living with HIV. The median travel time was approximately 2 hours. Using a reference group of stage I disease and a travel time of < 1 hour, the odds of presenting with stage II increased for patients traveling 3-5 hours (adjusted odds ratio [OR], 2.00; 95% CI, 1.14 to 3.52) and > 5 hours (OR, 2.19; 95% CI, 1.15 to 4.19). There were no significant associations for stage III. For stage IV disease, the odds were increased for patients traveling 3-5 hours (OR, 2.93; 95% CI, 1.26 to 6.79) and > 5 hours (adjusted OR, 4.05; 95% CI, 1.62 to 10.10). In addition, the odds of patients presenting living with HIV increased with increasing travel time (trend test = 0.004). CONCLUSION: This study identified two potential factors, travel time and HIV status, that influence access to comprehensive cervical cancer care in Botswana.

Evaluating the geographic distribution of cervical cancer patients presenting to a multidisciplinary gynecologic oncology clinic in Gaborone, Botswana.

OBJECTIVE: In Botswana, cervical cancer is the leading cause of cancer death for females. With limited resources, Botswana is challenged to ensure equitable access to advanced cancer care. Botswana's capital city, Gaborone, houses the only gynecologic oncology multi-disciplinary team (MDT) and the one chemoradiation facility in the country. We aimed to identify areas where fewer women were presenting to the MDT clinic for care. METHODS: This cross-sectional study examined cervical cancer patients presenting to the MDT clinic between January 2015 and March 2020. Patients were geocoded to residential sub-districts to estimate age-standardized presentation rates. Global Moran's I and Anselin Local Moran's I tested the null hypothesis that presentation rates occurred randomly in Botswana. Community- and individual-level factors of patients living in sub-districts identified with higher (HH) and lower (LL) clusters of presentation rates were examined using ordinary least squares with a spatial weights matrix and multivariable logistic regression, respectively, with α level 0.05. RESULTS: We studied 990 patients aged 22-95 (mean: 50.6). Presentation rates were found to be geographically clustered across the country (p = 0.01). Five sub-districts were identified as clusters, two high (HH) sub-district clusters and three low (LL) sub-district clusters (mean presentation rate: 35.5 and 11.3, respectively). Presentation rates decreased with increased travel distance (p = 0.033). Patients residing in LL sub-districts more often reported abnormal vaginal bleeding (aOR: 5.62, 95% CI: 1.31-24.15) compared to patients not residing in LL sub-districts. Patients in HH sub-districts were less likely to be living with HIV (aOR: 0.59; 95% CI: 0.38-0.90) and more likely to present with late-stage cancer (aOR: 1.78; 95%CI: 1.20-2.63) compared to patients not in HH sub-districts. CONCLUSIONS: This study identified geographic clustering of cervical cancer patients presenting for care in Botswana and highlighted sub-districts with disproportionately lower presentation rates. Identified community- and individual level-factors associated with low presentation rates can inform strategies aimed at improving equitable access to cervical cancer care.

Patient perspectives on delays in cervical cancer screening and follow-up care in Botswana: a mixed methods study.

BACKGROUND: Delays in screening and timely diagnosis contribute significantly to global disparities in cervical cancer mortality in Botswana and other low- and middle-income countries, particularly those with high rates of HIV. Little is known about the modifiable factors shaping these delays from the perspectives of women themselves and how these perspectives may differ between those living with and without HIV. METHODS: From March-May 2019, we conducted a concurrent, mixed methods study of women receiving treatment for cervical cancer at a multidisciplinary oncology clinic in Botswana. Enrolled participants completed a one-time, concurrent semi-structured interview and structured questionnaire assessing patient characteristics, screening and HIV-related beliefs and knowledge, and barriers and facilitators to screening and follow-up care. Qualitative data were analyzed using directed content analysis guided by the Model of Pathways to Treatment and triangulated with quantitative questionnaire data to identify areas of convergence and divergence. Fisher's exact tests were used to explore associations between questionnaire data (e.g., screening knowledge) and HIV status. RESULTS: Forty-two women enrolled in the study, 64% of whom were living with HIV and 26% were diagnosed with stage III cervical cancer. Median age was 45 years (IQR 54-67) in those living with HIV and 64 years (IQR 42-53) in those living without. Overall screening rates before symptomatic disease were low (24%). Median time from most proximal screen to diagnosis was 52 median days (IQR 15-176), with no significant differences by HIV status. General screening knowledge was higher among those living with HIV versus those without (100% vs 73%; p < 0.05), but knowledge about HPV and other risk factors was low in both groups. Similar to questionnaire results, qualitative results indicate limited awareness of the need to be screened prior to symptoms as a central barrier to timely screening. Some participants also noted that delays in the receipt of screening results and fear also contributed to treatment delays. However, many participants also described myriad sources of social and tangible support that helped them to overcome some of these challenges. CONCLUSION: Interventions focused on increasing routine screening and supporting timely awareness and access to care are needed to reduce global disparities in cervical cancer.

Risk factors for breast cancer subtypes among Black women undergoing screening mammography.

PURPOSE: Black women are more likely than non-Hispanic White women to be diagnosed with triple negative breast cancer (TNBC), an aggressive subtype with limited treatment options. The study objective was to evaluate the associations of known breast cancer risk factors, including breast density, with TNBC among Black women. METHODS: This study included Black women who underwent screening mammography between the ages of 40-84 years at a University of Pennsylvania Health System between 2010 and 2015. Cox proportional hazard models using multiple imputation with chained equations were used to estimate hazard ratios and 95% confidence intervals for risk factors for ER/PR+/HER2- and TNBC. RESULTS: Among 25,013 Black women, there were 330 incident breast cancers (1.3%) during a mean follow-up of 5.8 years; 218 (66.1%) ER/PR+ HER- and 61 (18.1%) TNBC. Having dense breasts (heterogeneously dense or extremely dense) vs. non-dense breasts (almost entirely fatty or scattered areas of fibroglandular density) increased risk of ER/PR+/HER2- breast cancer almost 80% (HR 1.79, 95% CI 1.32-2.43) and TNBC more than twofold (HR 2.53, 1.45-4.44). Older age was associated with an increased risk for ER/PR+/HER2- (HR 1.04, 1.03-1.06) and TNBC (HR 1.03, 1.00-1.05). Having a BMI of > 30 kg/m2 was associated with an increased risk (HR 2.77, 1.05-7.30) for TNBC and an increased risk of ERPR+/HER2- breast cancer in postmenopausal but not pre-menopausal women (p-interaction = 0.016). CONCLUSION: Our results suggest that breast density and obesity are strong risk factors for TNBC among Black women. Understanding breast cancer subtype specific risk factors among Black women can help improve risk assessment.

Clinical and sociodemographic factors associated with late stage cervical cancer diagnosis in Botswana.

BACKGROUND: Cervical cancer is the leading cause of female cancer mortality in Botswana with the majority of cervical cancer patients presenting with late-stage disease. The identification of factors associated with late-stage disease could reduce the cervical cancer burden. This study aims to identify potential patient level clinical and sociodemographic factors associated with a late-stage diagnosis of cervical cancer in Botswana in order to help inform future interventions at the community and individual levels to decrease cervical cancer morbidity and mortality. RESULTS: There were 984 women diagnosed with cervical cancer from January 2015 to March 2020 at two tertiary hospitals in Gaborone, Botswana. Four hundred forty women (44.7%) presented with late-stage cervical cancer, and 674 women (69.7%) were living with HIV. The mean age at diagnosis was 50.5 years. The association between late-stage (III/IV) cervical cancer at diagnosis and patient clinical and sociodemographic factors was evaluated using multivariable logistic regression with multiple imputation. Women who reported undergoing cervical cancer screening had lower odds of late-stage disease at diagnosis (OR: 0.63, 95% CI 0.47-0.84) compared to those who did not report screening. Women who had never been married had increased odds of late-stage disease at diagnosis (OR: 1.35, 95% CI 1.02-1.86) compared to women who had been married. Women with abnormal vaginal bleeding had higher odds of late-stage disease at diagnosis (OR: 2.32, 95% CI 1.70-3.16) compared to those without abnormal vaginal bleeding. HIV was not associated with a diagnosis of late-stage cervical cancer. Rural women who consulted a traditional healer had increased odds of late-stage disease at diagnosis compared to rural women who had never consulted a traditional healer (OR: 1.61, 95% CI 1.02-2.55). CONCLUSION: Increasing education and awareness among women, regardless of their HIV status, and among providers, including traditional healers, about the benefits of cervical cancer screening and about the importance of seeking prompt medical care for abnormal vaginal bleeding, while also developing support systems for unmarried women, may help reduce cervical cancer morbidity and mortality in Botswana.