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).

Cervical Cancer: Precursors and Prevention.

Cervical cancer, caused due to oncogenic types of human papillomavirus (HPV), is a leading preventable cause of cancer morbidity and mortality globally. Chronic, persistent HPV infection-induced cervical precursor lesions, if left undetected and untreated, can progress to invasive cancer. Cervical cancer screening approaches have evolved from cytology (Papanicolaou test) to highly sensitive HPV-based molecular methods and personalized, risk-stratified, management guidelines. Innovations like self-collection of samples to increase screening access, innovative triage methods to optimize management of screen positives, and scalable and efficacious precancer treatment approaches will be key to further enhance the utility of prevention interventions.

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.

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.

Primary Human Papillomavirus Testing and Other New Technologies for Cervical Cancer Screening.

Cervical cancer screening has saved the lives of millions in regions where routine gynecologic care is readily accessible. As screening continues to evolve away from cervical cytology to primary human papillomavirus (HPV) testing, robust prospective cohort data have allowed for precise risk stratification and improved our ability to identify those at greatest risk of high-grade dysplasia and decrease unnecessary diagnostic procedures. New technologies such as p16/Ki-67 dual stain testing and HPV methylation panels, which offer comparable performance to co-testing and can be developed into high-throughput workflows, could lead to a fully molecular Pap test. Self-sampling in the United States, where the initial screen can be done in the home, in conjunction with new screening technologies, may decrease the existing hurdles of routine cervical cancer screening. Implementation barriers include issues with workflow, workforce, and cost. These need to be addressed to achieve an improved and more equitable cervical cancer screening program in the United States.

Feasibility of 5-fluorouracil and imiquimod for the topical treatment of cervical intraepithelial neoplasias (CIN) 2/3.

OBJECTIVES: To determine the feasibility (as measured by tolerability and safety) and efficacy of topical 5-fluorouracil (5-FU) and imiquimod for the treatment of cervical intraepithelial neoplasia (CIN) 2/3. METHODS: This pilot prospective study was conducted in women aged 18-45 years with p16+ CIN 2/3. Participants underwent an 8-week alternating regimen of self-applied 5% 5-FU on weeks 1, 3, 5, and 7 and physician-applied imiquimod on weeks 2, 4, 6, and 8. Adverse events (AEs) were collected by symptom diary and clinical exam. Feasibility was measured by tolerability and safety (AEs) of the study intervention. Tolerability was assessed as the number of participants able to apply 50% or more of the treatment doses. The safety outcome was calculated as the number of participants who experienced "specified AEs" defined as possibly, probably, or definitely related grade 2 or worse AE or grade 1 genital AEs (blisters, ulcerations, or pustules) lasting more than 5 days. The efficacy of the intervention was determined by histology and high-risk human papillomavirus (hrHPV) testing was done after treatment. RESULTS: The median age of the 13 participants was 27 ± 2.9 years. Eleven (84.61%) participants applied 50% or more of the treatment. All participants reported grade 1 AEs; 6 (46.15%) reported grade 2 AEs; and 0 reported grade 3/4 AEs. Three (23.08%) participants had specified AEs. Histologic regression to normal or CIN 1 among those completing 50% or more of the treatment doses was observed in 10 (90.91%) participants, and 7 (63.63%) tested negative for hr-HPV at the end of the study. CONCLUSIONS: Topical treatment for CIN 2/3 with 5-FU/imiquimod is feasible, with preliminary evidence of efficacy. Topical therapies need further investigation as adjuncts or alternatives to surgical therapy for CIN 2/3.

HPV16/18 Antibody Responses After a Single Dose of Nonavalent HPV Vaccine.

OBJECTIVES: A single dose of human papillomavirus (HPV) vaccine would simplify logistics and reduce costs of vaccination programs worldwide. We conducted a phase IIa trial to determine the stability of HPV type-specific antibody responses after a single dose of the nonavalent HPV vaccine, Gardasil9. METHODS: Two hundred-and-one healthy 9 to 11-year-old girls and boys were enrolled at 2 centers in the United States to receive a prime dose of the nonavalent vaccine at baseline, a delayed dose at month 24, and an optional third dose at month 30. Blood samples were collected to measure HPV type-specific antibodies at baseline and at 6, 12, 18, 24, and 30 months after the prime dose. The primary outcomes were serum HPV16 and HPV18 antibody responses. RESULTS: In both girls and boys, geometric mean concentrations of HPV16 and HPV18 antibodies increased at 6 months, declined between months 6 to 12, and then remained stable and high (at 20- and 10-times those at baseline for HPV16 and HPV18, respectively) throughout months 12, 18, and 24 (prebooster) visits. Both HPV16 and HPV18 antibody responses demonstrated anamnestic boosting effect at 30-months after the delayed (24-month) booster dose. CONCLUSIONS: A single dose of the nonavalent HPV vaccine induced persistent and stable HPV16 and HPV18 antibody responses up to 24 months. This study contributes important immunogenicity data to inform feasibility of the single dose HPV vaccination paradigm. Further research is needed to assess the long-term antibody stability and individual clinical and public health benefit of the single dose schedule.

Diversity of Anal HPV and Non-HPV Sexually Transmitted Infections and Concordance with Genital Infections in HIV-Infected and HIV-Uninfected Women in the Tapajós Region, Amazon, Brazil.

The aim of this study was to classify the diversity of anal HPV and non-HPV sexually transmitted infections (STIs) and compare the concordance between anal and genital infections in HIV-infected and uninfected women living in the Tapajós region, Amazon, Brazil. A cross-sectional study was performed with 112 HIV-uninfected and 41 HIV-infected nonindigenous women. Anal and cervical scrapings were collected and analyzed for HPV, Chlamydia trachomatis (CT), Neisseria gonorrheae (NG), Trichomonas vaginalis (TV), Mycoplasma genitalium (MG), and Human alphaherpesvirus 2 (HSV-2). The Kappa test evaluated the concordance between anal and genital infections. The overall prevalence of anal HPV infection was 31.3% in HIV-uninfected and 97.6% in HIV-infected women. The most frequent anal high-risk HPV (hrHPV) types were HPV18 and HPV16 in HIV-uninfected women and HPV51, HPV59, HPV31, and HPV58 in HIV-infected women. Anal HPV75 Betapapillomavirus was also identified. Anal non-HPV STIs were identified in 13.0% of all participants. The concordance analysis was fair for CT, MG, and HSV-2, almost perfect agreement for NG, moderate for HPV, and variable for the most frequent anal hrHPV types. Thus, a high prevalence of anal HPV infection with moderate and fair concordance between anal and genital HPV and non-HPV STIs was observed in our study.

A Systematic Review and Pooled Analysis of Hypothesized versus Observed Effect Sizes in Early Phase Cancer Prevention Clinical Trials.

Early phase cancer prevention trials are designed to demonstrate safety, tolerability, feasibility, and signals of efficacy of preventive agents. Yet it is often observed that many trials fail to detect intervention effects. We conducted a systematic review and pooled analyses of recently completed early phase chemoprevention trials to gain in depth insight on the failure of detecting efficacy signals by comparing hypothesized effect sizes to the corresponding observed effect sizes.Single- or multi-arm efficacy chemoprevention trials conducted under the phase 0/I/II Cancer Prevention Clinical Trials Program of the Division of Cancer Prevention, NCI between 2003 and 2019 were evaluated. A total of 59 chemoprevention trials were reviewed. Twenty-four studies were efficacy or biomarker trials with complete information on hypothesized and observed effect sizes and included in this analysis. The majority of the trials (n = 18) were multi-arm randomized studies of which 15 trials were blinded. The pooled estimate of the observed to hypothesized effect size ratio was 0.57 (95% confidence interval: 0.42-0.73, P < 0.001) based on a random-effects model. There were no significant differences detected in the ratio of observed to hypothesized effect sizes when conducting various subgroup analyses.The results demonstrate that the majority of early phase cancer chemoprevention trials have substantially smaller observed effect sizes than hypothesized effect sizes. Sample size calculations for early phase chemoprevention trials need to balance the potential detectable effect sizes with realistic and cost-effective accrual of study populations, thereby, detecting only intervention effects large enough to justify subsequent large-scale confirmatory trials. PREVENTION RELEVANCE: The results of this systematic review and pooled analyses demonstrate that for early chemoprevention trials, there are substantial differences between hypothesized and observed effect sizes, regardless of study characteristics. The conduct of early phase chemoprevention trial requires careful planning of study design, primary endpoint, and sample size determination.

Lessons Learned from the Impact of COVID-19 on NCI-sponsored Cancer Prevention Clinical Trials: Moving Toward Participant-centric Study Designs.

The COVID-19 pandemic overloaded health care systems around the globe and brought travel restrictions and other mandates. These effects critically impacted cancer care and conduct of clinical trials, and required medical and research communities to incorporate changes and novel flexible workflows within clinical trials and regulations to improve efficiency. We report the impact of the pandemic on cancer prevention clinical trials managed by the Division of Cancer Prevention within the NCI, focusing on participant-centric, study staff-centric and regulatory elements. Learning lessons from this challenging period, the cancer prevention community has the opportunity to incorporate many of these necessitated novel approaches to future design of clinical trials, to streamline and improve clinical trial efficiency and impact.

A Randomized Clinical Trial of Human Papillomavirus Test-and-Treat as Compared to Cytology-Based Screening for Prevention of Cervical Cancer Among Women With Human Immunodeficiency Virus: AIDS Clinical Trials Group Protocol A5282.

BACKGROUND: Cytology-based cervical cancer screening followed by confirmation and treatment of biopsy-proven high-grade squamous intraepithelial lesions (bHSIL) is difficult to implement in resource-constrained settings. We hypothesized that high-risk human papillomavirus (hrHPV) testing followed by immediate cryotherapy of women with hrHPV (HPV screen-and-treat) may improve outcomes. METHODS: Randomized, open-label, phase 2, multinational clinical trial enrolling women with human immunodeficiency virus (HIV) age 18 or older with cervical hrHPV and having no cervical lesions or lesions appropriate for cryotherapy. Women were randomized to immediate cryotherapy (Arm A) or cytology-based screening (Arm B). For Arm A, cervical biopsies were obtained followed by cervical cryotherapy, and in Arm B, women with abnormal cytology underwent colposcopy followed by loop electroexcision procedure (LEEP) if bHSIL was detected. Women were followed through 30 months. The primary outcome was time to bHSIL detected from Month 6 through study completion. RESULTS: In total, 288 women (145 in Arm A, 143 in Arm B) were randomized: median age 35 years, 84% on antiretroviral therapy, median CD4 501 cells/mm3. In Arm A, 39 (27%) of women had bHSIL at entry, and in Arm B, 88 (62%) had abnormal cytology, 22 (15%) were diagnosed with bHSIL, 12 (8%) underwent LEEP. In follow-up, 30 (21%) and 31 (22%) developed bHSIL; time to bHSIL was similar between arms (P=.94). The prevalence of hrHPV at Month 6 was similar between arms (61% and 70%, P=.13). CONCLUSIONS: HPV test-and-treat was not associated with improved bHSIL outcomes as compared to cytology-based screening. More effective treatment options are required to improve outcomes from screen-and-treat programs. CLINICAL TRIALS REGISTRATION: NCT01315363.

Meta-analysis of agreement/concordance statistics in studies comparing self- vs clinician-collected samples for HPV testing in cervical cancer screening.

We conducted a meta-analysis of test agreement/concordance between human papillomavirus (HPV) testing in self-collected vs clinician-collected samples in 26 studies (10 071 participants) updating a previous meta-analysis on accuracy for cervical precancer. Pooled overall agreement was 88.7% (95% CI: 86.3%-90.9%), positive agreement was 84.6% (95% CI: 79.9%-88.7%), negative agreement was 91.7% (95% CI: 89.1%-94.0%) and kappa was 0.72 (95% CI: 0.66-0.78). Subgroup meta-analyses suggested higher overall agreement for target amplification-based DNA assays (90.4%) compared to signal amplification-based DNA assays (86.7%; P = .175) or RNA assays (82.3%; P < .001). HPV test agreement/concordance targets may provide criteria to extend existing validations toward alternative sampling approaches and devices/storage media.

The development of "automated visual evaluation" for cervical cancer screening: The promise and challenges in adapting deep-learning for clinical testing: Interdisciplinary principles of automated visual evaluation in cervical screening.

There is limited access to effective cervical cancer screening programs in many resource-limited settings, resulting in continued high cervical cancer burden. Human papillomavirus (HPV) testing is increasingly recognized to be the preferable primary screening approach if affordable due to superior long-term reassurance when negative and adaptability to self-sampling. Visual inspection with acetic acid (VIA) is an inexpensive but subjective and inaccurate method widely used in resource-limited settings, either for primary screening or for triage of HPV-positive individuals. A deep learning (DL)-based automated visual evaluation (AVE) of cervical images has been developed to help improve the accuracy and reproducibility of VIA as assistive technology. However, like any new clinical technology, rigorous evaluation and proof of clinical effectiveness are required before AVE is implemented widely. In the current article, we outline essential clinical and technical considerations involved in building a validated DL-based AVE tool for broad use as a clinical test.

Cervical cancer prevention and control in women living with human immunodeficiency virus.

Despite being highly preventable, cervical cancer is the fourth most common cancer and cause of cancer death in women globally. In low-income countries, cervical cancer is often the leading cause of cancer-related morbidity and mortality. Women living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome are at a particularly high risk of cervical cancer because of an impaired immune response to human papillomavirus, the obligate cause of virtually all cervical cancers. Globally, approximately 1 in 20 cervical cancers is attributable to HIV; in sub-Saharan Africa, approximately 1 in 5 cervical cancers is due to HIV. Here, the authors provide a critical appraisal of the evidence to date on the impact of HIV disease on cervical cancer risk, describe key methodologic issues, and frame the key outstanding research questions, especially as they apply to ongoing global efforts for prevention and control of cervical cancer. Expanded efforts to integrate HIV care with cervical cancer prevention and control, and vice versa, could assist the global effort to eliminate cervical cancer as a public health problem.

Infiltrating T-cell markers in cervical carcinogenesis: a systematic review and meta-analysis.

BACKGROUND: The host adaptive immune response helps determine which cervical HPV infections persist and progress to precancer and cancer, and systematic characterisation of T-cell infiltration would help inform key steps in cervical carcinogenesis. METHODS: A systematic review and meta-analysis were conducted of infiltrating T-cells in normal cervix, low-grade lesions, high-grade lesions, and invasive cancers including epithelial, stromal, and total tissue and the following markers: CD3, CD4, CD8, FoxP3, CD25, and the CD4:CD8 ratio. An additional qualitative review summarised longitudinal data on associations between infiltrating T-cells and cervical disease persistence, regression, progression, or prognosis. RESULTS: There were fewer CD3+, CD4+, and CD8+ cells in cervical lesions and more cells in cancers compared to normal epithelium. FoxP3 and CD25+ regulatory T-cell infiltration is high in persistent and precancerous lesions, and longitudinal data show improved outcomes with lower regulatory T-cell levels. CONCLUSIONS: Successful immune evasion may reduce T-cell infiltration in HPV infected and precancerous epithelium, while invasive cancers are highly immunogenic, and regulatory T-cell infiltration increases with cervical disease progression. Understanding these factors may have prognostic value and could aid in novel treatment development and clinical guidelines, but published data are highly heterogeneous and leave important gaps to be filled by future studies.

A prospective, single-arm, open-label, non-randomized, phase IIa trial of a nonavalent prophylactic HPV vaccine to assess immunogenicity of a prime and deferred-booster dosing schedule among 9-11 year-old girls and boys - clinical protocol.

BACKGROUND: Human papillomavirus (HPV) vaccines are indicated for the prevention of cancers and genital warts caused by vaccine-covered HPV types. Although the standard regimen requires a two or three-dose vaccine series, there is emerging data suggesting that a single dose of the bivalent or quadrivalent HPV vaccine generates persistently positive antibody titers. No similar data is yet available for the nonavalent HPV vaccine, currently the only HPV vaccine available in the United States. The overall objective of our study is to assess the stability and kinetics of antibody titers for 24 months following a single dose of the nonavalent HPV vaccine among preteen girls and boys. METHODS: This is a prospective, single-arm, open-label, non-randomized, Phase IIa trial among 9-11 year-old girls and boys to determine the immunogenicity after a single dose of the nonavalent HPV vaccine (GARDASIL® 9) over 24 months, with a deferred booster dose at 24 months and an optional booster at 30 months after the first dose. Participants provide blood specimens at 6, 12, 18, 24, and 30 months after the first dose. Serologic geometric mean titers (GMT) of the nine vaccine types (HPV 16/18/ 6/11/31/33/45/52/58) will be measured at each time point. The primary objective is to determine the stability of type-specific serologic GMT of HPV16 and HPV18 between the 6- vs. 12-month, 12- vs. 18-month, and 18- vs. 24-month visits. Secondary objectives are to determine the stability of type-specific serologic GMT of the other HPV types (HPV 6/11/31/33/45/52/58) between the visits and to assess safety and reactogenicity after each vaccine dose. DISCUSSION: Single dose HPV vaccination could simplify the logistics and reduce costs of HPV vaccination in the US and across the world. This study will contribute important immunogenicity data on the stability and kinetics of type-specific antibody titers and inform feasibility of the single dose HPV vaccination paradigm. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02568566 . Registered on October 6, 2015.

A tailored approach to building specialized surgical oncology capacity: Early experiences and outcomes in Malawi.

OBJECTIVES: Cervical cancer can often be cured by surgery alone, if diagnosed and treated early. However, of the cancer patients who live in the world's poorest countries less that 5% have access to safe, effective and timely cancer surgery. We designed a novel, competency-based curriculum to rapidly build surgical capacity for the treatment of cervical cancer. Here we report experiences and early outcomes of its implementation in Malawi. METHODS: Curriculum implementation consisted of preoperative evaluation of patients and surgical video review, discussion of surgical instruments and suture material, deconstruction of the surgical procedure into critical subcomponents including trainees walking through the steps of the procedure with the master trainers, high-volume surgical repetition over a short time interval, intra-operative mentoring, post-operative case review, and mental narration. This was preceded by self-directed learning and followed by clinical mentorship through electronic communication and quarterly on-site visits. RESULTS: Between June 2015-June 2017, 28 patients underwent radical abdominal hysterectomy with bilateral pelvic lymphadenectomy. The first 8 surgeries were performed over 5 days. After the 7th case the trainee could perform the procedure alone. During and between quarterly mentoring-visits the trainee independently performed the procedure on 20 additional patients. Major surgical complications were rare. CONCLUSIONS: Life-saving surgical treatment for cervical cancer is now available for the first time, as a routine clinical service, in Central/Northern, Malawi.

Leverage of an Existing Cervical Cancer Prevention Service Platform to Initiate Breast Cancer Control Services in Zambia: Experiences and Early Outcomes.

PURPOSE: In 2005, the Cervical Cancer Prevention Program in Zambia (CCPPZ) was implemented and has since provided cervical cancer screen-and-treat services to more than 500,000 women. By leveraging the successes and experiences of the CCPPZ, we intended to build capacity for the early detection and surgical treatment of breast cancer. METHODS: Our initiative sought to build capacity for breast cancer care through the (1) formation of a breast cancer advocacy alliance to raise awareness, (2) creation of resource-appropriate breast cancer care training curricula for mid- and high-level providers, and (3) implementation of early detection and treatment capacity within two major health care facilities. RESULTS: Six months after the completion of the initiative, the following outcomes were documented: Breast health education and clinical breast examination (CBE) services were successfully integrated into the service platforms of four CCPPZ clinics. Two new breast diagnostic centers were opened, which provided access to breast ultrasound, ultrasound-guided core needle biopsy, and needle aspiration. Breast health education and CBE were provided to 1,955 clients, 167 of whom were evaluated at the two diagnostic centers; 55 of those evaluated underwent core-needle biopsy, of which 17 were diagnosed with invasive cancer. Newly trained surgeons performed six sentinel lymph node mappings, eight sentinel lymph node dissections, and 10 breast conservation surgeries (lumpectomies). CONCLUSION: This initiative successfully established clinical services in Zambia that are critical for the early detection and surgical management of breast cancer.