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 .

Internal validation of Automated Visual Evaluation (AVE) on smartphone images for cervical cancer screening in a prospective study in Zambia.

OBJECTIVES: Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other visual tests, is subjective and requires sustained training and quality assurance. We developed, trained, and validated an artificial-intelligence-based "Automated Visual Evaluation" (AVE) tool that can be adapted to run on smartphones to assess smartphone-captured images of the cervix and identify precancerous lesions, helping augment VIA performance. DESIGN: Prospective study. SETTING: Eight public health facilities in Zambia. PARTICIPANTS: A total of 8204 women aged 25-55. INTERVENTIONS: Cervical images captured on commonly used low-cost smartphone models were matched with key clinical information including human immunodeficiency virus (HIV) and human papillomavirus (HPV) status, plus histopathology analysis (where applicable), to develop and train an AVE algorithm and evaluate its performance for use as a primary screen and triage test for women who are HPV positive. MAIN OUTCOME MEASURES: Area under the receiver operating curve (AUC); sensitivity; specificity. RESULTS: As a general population screening tool for cervical precancerous lesions, AVE identified cases of cervical precancerous and cancerous (CIN2+) lesions with high performance (AUC = 0.91, 95% confidence interval [CI] = 0.89-0.93), which translates to a sensitivity of 85% (95% CI = 81%-90%) and specificity of 86% (95% CI = 84%-88%) based on maximizing the Youden's index. This represents a considerable improvement over naked eye VIA, which as per a meta-analysis by the World Health Organization (WHO) has a sensitivity of 66% and specificity of 87%. For women living with HIV, the AUC of AVE was 0.91 (95% CI = 0.88-0.93), and among those testing positive for high-risk HPV types, the AUC was 0.87 (95% CI = 0.83-0.91). CONCLUSIONS: These results demonstrate the feasibility of utilizing AVE on images captured using a commonly available smartphone by nurses in a screening program, and support our ongoing efforts for moving to more broadly evaluate AVE for its clinical sensitivity, specificity, feasibility, and acceptability across a wider range of settings. Limitations of this study include potential inflation of performance estimates due to verification bias (as biopsies were only obtained from participants with visible aceto-white cervical lesions) and due to this being an internal validation (the test data, while independent from that used to develop the algorithm was drawn from the same study).

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.

Three-year survival of breast cancer patients attending a one-stop breast care clinic nested within a primary care health facility in sub-Saharan Africa-Zambia.

In Zambia, women with breast symptoms travel through multiple levels of the healthcare system before obtaining a definitive diagnosis. To eradicate this critical barrier to care, we nested a novel breast specialty service platform inside a large public-sector primary healthcare facility in Lusaka, Zambia to offer clinical breast examination, breast ultrasound, and ultrasound-guided core needle biopsy in a one-stop format, tightly linked to referral for treatment. The objective of the study was to determine the life expectancy and survival outcomes of a prospective cohort of women diagnosed with breast cancer who were attended to and followed up at the clinic. The effect of breast cancer stage on prognosis was determined by estimating stage-specific crude survival using the Kaplan-Meier method. Survival analysis was used to estimate mean lifespan according to age and stage at diagnosis. We enrolled 302 women with histologically confirmed breast cancer. The overall 3-year survival was 73%. An increase in patients presenting with early breast cancer and improvements in their survival were observed. Women with early-stage breast cancer had a lifespan similar to the general population, while loss of life expectancy was significant at more advanced stages of disease. Our findings suggest that implementing efficient breast care services at the primary care level can avert a substantial proportion of breast cancer-related deaths. The mitigating factor appears to be stage of disease at the time of diagnosis, the cause of which is multifactorial, with the most influential being delays in the referral process.

Racial disparities in endometrial cancer: Where are we after 26 years?

INTRODUCTION: Endometrial cancer is the most commonly diagnosed female genital tract malignancy in the United States of America. Racial disparities surrounding this particular disease have been extensively investigated for over 26-years. We sought to determine if research in this area has led to any significant improvements in this disparity. METHODS: We performed a rapid systematic review of English language publications on racial disparities in endometrial cancer among African American (AAW) and white American women (WAW), from 1997 to 2023. We looked at trends in incidence and survival; impact of known poor prognostic factors (stage at diagnosis, histological subtypes, grade); co-morbidities; differences in treatment (surgery, radiation and chemotherapy); socioeconomic factors; differences in biological and genetic markers; and policies/declarations. RESULTS: During the period under review (1997-2023), there was a notable increase in both disease incidence (39%) and mortality (26%) rates for AAW, in comparison to WAW among whom the incidence rates increased by 2% and mortality rates rose, but 9% less than for AAW. It should be noted that the current incidence rate of 29.4% in AAW represent a reversal of what is was 26-years ago, when the incidence rate was 17.8%. In comparison to WAW, AAW had a higher prevalence of poor prognostic variables, more co-morbidities, lower income levels, less insurance coverage, and were more frequently under treated with surgery, chemotherapy and radiation. To date no actionable molecular/genetic markers have been identified. We were unable to locate any published recommendations or active programs of implementation strategies/policies designed to effectively mitigate the documented racial disparity. CONCLUSION: Racial disparities in disease incidence and mortality in endometrial cancer rates between WAW and AAW have widened during a 26-year period of robust research, suggesting that current research alone is not enough to eliminate this disparity. Based on this rapid systematic review we have identified and analyzed the impact of causation variables on this disparity. Additionally, we have made strong and pertinent recommendations for the benefit of mitigating this escalating racial disparity.

The impact of Black founding fathers on the specialty of gynecologic oncology.

INTRODUCTION: The formative period of the specialty of gynecologic oncology was from 1968 to 1972 and became a board-certified specialty in 1973. During this formation there were no Black physicians participating in this process. We chronicle and document the incorporation of the first three board-certified Black physicians in the specialty of gynecologic oncology here for historical purposes. METHODS: We highlight the hostile climate experienced by Black physicians before and during the formation of gynecologic oncology, review the acceptance and training of the first three Black physicians in the specialty and recognize their significant contributions to the field. RESULTS: The biographies and the narrative of these men describe their impact and contribution to medicine. We chronicle the historic presence of the first board-certified Black gynecologic oncologists and pelvic surgeons in the United States. CONCLUSION: These three men represent the Black Founding Fathers of gynecologic oncology. Their perseverance in the face of adversity and commitment to excellence have left an indelible impact on the institutions that they developed, the individuals that they trained, and the patients that they served.

Inequities in global cancer surgery: Challenges and solutions.

The disparity in access to and quality of surgical cancer care between high and low resource settings impacts immediate and long-term oncological outcomes. With cancer incidence and mortality set to increase rapidly in the next few decades, we examine the factors leading to inequities in global cancer surgery, and look at potential solutions to overcome these challenges.

Internal Validation of Automated Visual Evaluation (AVE) on Smartphone Images for Cervical Cancer Screening in a Prospective Study in Zambia.

Objectives: Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other visual tests like histopathology, is subjective and requires sustained training and quality assurance. We developed, trained, and validated an artificial-intelligence-based "Automated Visual Evaluation" (AVE) tool that can be adapted to run on smartphones to assess smartphone-captured images of the cervix and identify precancerous lesions, helping augment performance of VIA. Design: Prospective study. Setting: Eight public health facilities in Zambia. Participants: 8,204 women aged 25-55. Interventions: Cervical images captured on commonly used low-cost smartphone models were matched with key clinical information including human immunodeficiency virus (HIV) and human papillomavirus (HPV) status, plus histopathology analysis (where applicable), to develop and train an AVE algorithm and evaluate its performance for use as a primary screen and triage test for women who are HPV positive. Main outcome measures: Area under the receiver operating curve (AUC); sensitivity; specificity. Results: As a general population screening for cervical precancerous lesions, AVE identified cases of cervical precancerous and cancerous (CIN2+) lesions with high performance (AUC = 0.91, 95% confidence interval [CI] = 0.89 to 0.93), which translates to a sensitivity of 85% (95% CI = 81% to 90%) and specificity of 86% (95% CI = 84% to 88%) based on maximizing the Youden's index. This represents a considerable improvement over VIA, which a meta-analysis by the World Health Organization (WHO) estimates to have sensitivity of 66% and specificity of 87%. For women living with HIV, the AUC of AVE was 0.91 (95% CI = 0.88 to 0.93), and among those testing positive for high-risk HPV types, the AUC was 0.87 (95% CI = 0.83 to 0.91). Conclusions: These results demonstrate the feasibility of utilizing AVE on images captured using a commonly available smartphone by screening nurses and support our transition to clinical evaluation of AVE's sensitivity, specificity, feasibility, and acceptability across a broader range of settings. The performance of the algorithm as reported may be inflated, as biopsies were obtained only from study participants with visible aceto-white cervical lesions, which can lead to verification bias; and the images and data sets used for testing of the model, although "unseen" by the algorithm during training, were acquired from the same set of patients and devices, limiting the study to that of an internal validation of the AVE algorithm.

Improving access to safe, quality surgical care for gynecologic cancers through capacity-building interventions in low- and middle-income countries: A scoping review.

BACKGROUND: Following the launch of the World Health Organization's Strategy to accelerate the elimination of cervical cancer, diagnosis is expected to increase, especially in low- and middle-income countries (LMICs). A well-integrated surgical system is critical to treat cervical cancer. Two major approaches have been employed to build human capacity: task-sharing and training of gynecologic oncologists (GynOncs). OBJECTIVES: This review aimed to explore existing literature on capacity-building for surgical management of early-stage gynecologic cancers. SEARCH STRATEGY: The search strategy was registered on Open Science Framework (doi 10.17605/OSF.IO/GTRCB) and conducted on OVID Medline, Embase, Global Index Medicus, and Web of Science. Search results were exported and screened in COVIDENCE. SELECTION CRITERIA: Studies published in English, Spanish, French, and/or Portuguese conducted in LMIC settings evaluating capacity building, task-sharing, or outcomes following operation by subspecialists compared to specialists were included. DATA COLLECTION AND ANALYSIS: Results were synthesized using narrative synthesis approach with emergence of key themes by frequency. MAIN RESULTS: The scoping review identified 18 studies spanning our themes of interest: capacity building, subspecialized versus non-subspecialized care, and task-shifting/-sharing. CONCLUSIONS: A multilayered approach is critical to achieve the WHO Strategy to Eliminate Cervical Cancer. Capacity-building and task-sharing programs demonstrate encouraging results to meet this need; nevertheless, a standardized methodology is needed to evaluate these programs, their outcomes, and cost-effectiveness.

Validation in Zambia of a cervical screening strategy including HPV genotyping and artificial intelligence (AI)-based automated visual evaluation.

BACKGROUND: WHO has recommended HPV testing for cervical screening where it is practical and affordable. If used, it is important to both clarify and implement the clinical management of positive results. We estimated the performance in Lusaka, Zambia of a novel screening/triage approach combining HPV typing with visual assessment assisted by a deep-learning approach called automated visual evaluation (AVE). METHODS: In this well-established cervical cancer screening program nested inside public sector primary care health facilities, experienced nurses examined women with high-quality digital cameras; the magnified illuminated images permit inspection of the surface morphology of the cervix and expert telemedicine quality assurance. Emphasizing sensitive criteria to avoid missing precancer/cancer, ~ 25% of women screen positive, reflecting partly the high HIV prevalence. Visual screen-positive women are treated in the same visit by trained nurses using either ablation (~ 60%) or LLETZ excision, or referred for LLETZ or more extensive surgery as needed. We added research elements (which did not influence clinical care) including collection of HPV specimens for testing and typing with BD Onclarity™ with a five channel output (HPV16, HPV18/45, HPV31/33/52/58, HPV35/39/51/56/59/66/68, human DNA control), and collection of triplicate cervical images with a Samsung Galaxy J8 smartphone camera™ that were analyzed using AVE, an AI-based algorithm pre-trained on a large NCI cervical image archive. The four HPV groups and three AVE classes were crossed to create a 12-level risk scale, ranking participants in order of predicted risk of precancer. We evaluated the risk scale and assessed how well it predicted the observed diagnosis of precancer/cancer. RESULTS: HPV type, AVE classification, and the 12-level risk scale all were strongly associated with degree of histologic outcome. The AVE classification showed good reproducibility between replicates, and added finer predictive accuracy to each HPV type group. Women living with HIV had higher prevalence of precancer/cancer; the HPV-AVE risk categories strongly predicted diagnostic findings in these women as well. CONCLUSIONS: These results support the theoretical efficacy of HPV-AVE-based risk estimation for cervical screening. If HPV testing can be made affordable, cost-effective and point of care, this risk-based approach could be one management option for HPV-positive women.

Virtual reality and surgical oncology.

More than 80% of people diagnosed with cancer will require surgery. However, less than 5% have access to safe, affordable and timely surgery in low- and middle-income countries (LMICs) settings mostly due to the lack of trained workforce. Since its creation, virtual reality (VR) has been heralded as a viable adjunct to surgical training, but its adoption in surgical oncology to date is poorly understood. We undertook a systematic review to determine the application of VR across different surgical specialties, modalities and cancer pathway globally between January 2011 and 2021. We reviewed their characteristics and respective methods of validation of 24 articles. The results revealed gaps in application and accessibility of VR with a proclivity for high-income countries and high-risk, complex oncological surgeries. There is a lack of standardisation of clinical evaluation of VR, both in terms of clinical trials and implementation science. While all VR illustrated face and content validity, only around two-third exhibited construct validity and predictive validity was lacking overall. In conclusion, the asynchrony between VR development and actual global cancer surgery demand means the technology is not effectively, efficiently and equitably utilised to realise its surgical capacity-building potential. Future research should prioritise cost-effective VR technologies with predictive validity for high demand, open cancer surgeries required in LMICs.

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).

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.

Global and regional estimates of orphans attributed to maternal cancer mortality in 2020.

Despite women being disproportionally affected by cancer deaths at young ages, there are no global estimates of the resulting maternal orphans, who experience health and education disadvantages throughout their lives. We estimated the number of children who became maternal orphans in 2020 due to their mother dying from cancer in that year, for 185 countries worldwide and by cause of cancer-related death. Female cancer deaths-by country, cancer type and age (derived from GLOBOCAN estimates)-were multiplied by each woman's estimated number of children under the age of 18 years at the time of her death (fertility data were derived from United Nations World Population Prospects for birth cohort), accounting for child mortality and parity-cancer risk associations. Globally, there were 1,047,000 such orphans. Over half of these were orphans due to maternal deaths from breast (258,000, 25%), cervix (210,000, 20%) and upper-gastrointestinal cancers (136,000, 13%), and most occurred in Asia (48%: India 15%, China 10%, rest of Asia 23%) and Africa (35%). Globally, there were 40 new maternal orphans due to cancer per 100,000 children, with a declining trend with a higher Human Development Index (range: 121 in Malawi to 15 in Malta). An estimated 7 million children were prevalent maternal orphans due to cancer in mid-2020. Accelerating the implementation of the World Health Organization's cervical and breast cancer initiatives has the potential to avert not only millions of preventable female cancer deaths but also the associated, often-overlooked, intergenerational consequences of these deaths.

Cancer research across Africa: a comparative bibliometric analysis.

INTRODUCTION: Research is a critical pillar in national cancer control planning. However, there is a dearth of evidence for countries to implement affordable strategies. The WHO and various Commissions have recommended developing stakeholder-based needs assessments based on objective data to generate evidence to inform national and regional prioritisation of cancer research needs and goals. METHODOLOGY: Bibliometric algorithms (macros) were developed and validated to assess cancer research outputs of all 54 African countries over a 12-year period (2009-2020). Subanalysis included collaboration patterns, site and domain-specific focus of research and understanding authorship dynamics by both position and sex. Detailed subanalysis was performed to understand multiple impact metrics and context relative outputs in comparison with the disease burden as well as the application of a funding thesaurus to determine funding resources. RESULTS: African countries in total published 23 679 cancer research papers over the 12-year period (2009-2020) with the fractional African contribution totalling 16 201 papers and the remaining 7478 from authors from out with the continent. The total number of papers increased rapidly with time, with an annual growth rate of 15%. The 49 sub-Saharan African (SSA) countries together published just 5281 papers, of which South Africa's contribution was 2206 (42% of the SSA total, 14% of all Africa) and Nigeria's contribution was 997 (19% of the SSA total, 4% of all Africa). Cancer research accounted for 7.9% of all African biomedical research outputs (African research in infectious diseases was 5.1 times than that of cancer research). Research outputs that are proportionally low relative to their burden across Africa are paediatric, cervical, oesophageal and prostate cancer. African research mirrored that of Western countries in terms of its focus on discovery science and pharmaceutical research. The percentages of female researchers in Africa were comparable with those elsewhere, but only in North African and some Anglophone countries. CONCLUSIONS: There is an imbalance in relevant local research generation on the continent and cancer control efforts. The recommendations articulated in our five-point plan arising from these data are broadly focused on structural changes, for example, overt inclusion of research into national cancer control planning and financial, for example, for countries to spend 10% of a notional 1% gross domestic expenditure on research and development on cancer.

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.

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.

Priorities for cancer research in low- and middle-income countries: a global perspective.

Cancer research currently is heavily skewed toward high-income countries (HICs), with little research conducted in, and relevant to, the problems of low- and middle-income countries (LMICs). This regional discordance in cancer knowledge generation and application needs to be rebalanced. Several gaps in the research enterprise of LMICs need to be addressed to promote regionally relevant research, and radical rethinking is needed to address the burning issues in cancer care in these regions. We identified five top priorities in cancer research in LMICs based on current and projected needs: reducing the burden of patients with advanced disease; improving access and affordability, and outcomes of cancer treatment; value-based care and health economics; quality improvement and implementation research; and leveraging technology to improve cancer control. LMICs have an excellent opportunity to address important questions in cancer research that could impact cancer control globally. Success will require collaboration and commitment from governments, policy makers, funding agencies, health care organizations and leaders, researchers and the public.

Disparities in breast cancer survival between women with and without HIV across sub-Saharan Africa (ABC-DO): a prospective, cohort study.

BACKGROUND: Studies have shown increased mortality among women living with HIV diagnosed with breast cancer compared with HIV-negative women with breast cancer. We aimed to examine how this HIV differential varies by patient or breast tumour characteristics. METHODS: The African Breast Cancer-Disparities in Outcomes (ABC-DO) study is a prospective cohort of women (aged ≥18 years) with incident breast cancer recruited consecutively at diagnosis (2014-17) from hospitals in Namibia, Nigeria, South Africa, Uganda, and Zambia. Detailed clinical and epidemiological data, including self-reported or tested HIV status, were collected at baseline. Participants were actively followed up via telephone calls every 3 months. The primary outcome was all-cause mortality, assessed in all women who had at least one updated vital status after baseline interview. Using Cox regression, we examined differences in overall survival by HIV status in the cohort, and across country and patient subgroups, adjusted for age, tumour grade, and tumour stage at cancer diagnosis. FINDINGS: Between Sept 8, 2014, and Dec 31, 2017, we recruited 2154 women with primary breast cancer, 519 of whom were excluded due to their countries having small numbers of women with HIV for comparison. Among the remaining 1635 women, 313 (19%) were living with HIV, 1184 (72%) were HIV negative, and 138 (9%) had unknown HIV status. At breast cancer diagnosis, women with HIV were younger and had lower body-mass index (BMI) than their HIV-negative counterparts, but had similar tumour stage, grade, and receptor subtypes. At the end of the follow-up (Jan 1, 2019), a higher proportion of women with HIV (137 [44%] of 313) had died than had HIV-negative women (432 [37%] of 1184). Crude 3-year survival was 9% lower for women with HIV (46% [95% CI 40-53]) than for HIV-negative women (55% [52-59]; hazard ratio (HR) 1·41 [1·15-1·74]). The HIV survival differential did not differ by age, BMI, tumour subtype, or tumour grade, but was stronger in women with non-metastatic disease (3-year survival 52% HIV-positive vs 63% HIV-negative women, adjusted HR 1·65 [1·30-2·10]), whereas women with metastatic cancer had low survival, regardless of HIV status. INTERPRETATION: The larger survival deficit among women with HIV with non-metastatic breast cancer calls for a better understanding of the reasons underlying this differential (eg, biological mechanisms, health behaviours, detrimental HIV-breast cancer treatment interactions, or higher HIV background mortality) to inform strategies for reducing mortality among this patient group. FUNDING: Susan G Komen, International Agency for Research on Cancer, National Cancer Institute, and UK-Commonwealth Scholarships.

Implementation research to accelerate scale-up of national screen and treat strategies towards the elimination of cervical cancer.

BACKGROUND: Cervical cancer is a significant public health problem, with 570,000 new cases and 300,000 deaths of women per year globally, mostly in low- and middle-income countries. In 2018 the WHO Director General made a call to action for the elimination of cervical cancer as a public health problem. MAIN BODY: New thinking on programmatic approaches to introduce emerging technologies and screening and treatment interventions of cervical precancer at scale is needed to achieve elimination goals. Implementation research (IR) is an important yet underused tool for facilitating scale-up of evidence-based screening and treatment interventions, as most research has focused on developing and evaluating new interventions. It is time for countries to define their specific IR needs to understand acceptability, feasibility, and cost-effectiveness of interventions as to design and ensure effective implementation, scale-up, and sustainability of evidence-based screening and treatment interventions. WHO convened an expert advisory group to identify priority IR questions for HPV-based screening and treatment interventions in population-based programmes. Several international organizations are supporting large scale introduction of screen-and-treat approaches in many countries, providing ideal platforms to evaluate different approaches and strategies in diverse national contexts. CONCLUSION: For reducing cervical cancer incidence and mortality, the readiness of health systems, the reach and effectiveness of new technologies and algorithms for increasing screening and treatment coverage, and the factors that support sustainability of these programmes need to be better understood. Answering these key IR questions could provide actionable guidance for countries seeking to implement the WHO Global Strategy towards cervical cancer elimination.