Introduction of HPV testing for cervical cancer screening in Central America: The Scale-Up project.

The Scale-Up project introduced vaginal self-sampling and low-cost human papillomavirus (HPV) testing as the primary approach for cervical cancer screening in selected public health centers in Guatemala, Honduras, and Nicaragua. We evaluate the country-specific accomplishments in screening: target-coverage, triage, and treatment. Between 2015 and 2018, cervical cancer screening was offered to women at least 30 years of age. Triage of HPV-positive women was based on visual inspection with acetic acid or Pap. Aggregated data included total women screened, use of self-sampling, age, time elapsed since last screening, HPV results, triage tests, triage results, and treatment. A total of 231,741 women were screened for HPV, representing 85.8% of the target populations within the project. HPV positivity was lower in Guatemala (12.4%) compared to Honduras and Nicaragua (14.5% and 14.2%, respectively, p < 0.05). A follow-up triage test was completed for 84.2%, 85.8%, and 50.1% of HPV-positive women in Guatemala, Nicaragua, and Honduras, respectively. Of those with a positive triage test, 84.7%, 67.1%, and 58.8% were treated in Guatemala, Nicaragua, and Honduras, respectively. First-time screening was highest in Nicaragua (55.8%) where self-sampling was also widely used (97.1%). The Scale-Up project demonstrated that large-scale cervical cancer screening and treatment intervention in a high-burden, low-resource setting can be achieved. Self-sampling and ablative treatment were key to the project's achievements. Data monitoring, loss to follow-up, and triage methods of screen- positive women remain critical to full success.

HPV-based cervical cancer screening in Nicaragua: from testing to treatment.

BACKGROUND: In Nicaragua, cervical cancer is the leading cause of cancer death among women. Human papillomavirus (HPV) testing, primarily using self-sampling, was introduced between 2014 and 2018 in three provinces. We analyzed data from the HPV screening program with the goal of describing key characteristics including reach, HPV prevalence, triage and treatment, and factors associated with follow-up completion. METHODS: We analyzed individual-level data from routinely collected forms for women attending HPV-based cervical cancer screening. HPV-positive women were triaged with Pap or visual inspection with acetic acid (VIA) prior to treatment. Logistic regression was used to identify factors associated with receiving triage and treatment; analyses were adjusted for province, age, and self- vs. provider-collected sampling. RESULTS: Forty-four thousand six hundred thirty-five women were screened with HPV testing; 96.6% of women used self-sampling. Six thousand seven hundred seventy-six women were HPV positive (15.2%), 54.0% of screen-positive women received triage, and 53.1% of triage-positive women were treated, primarily with cryotherapy. If women lost at triage are included, the overall treatment percentage was 27.8%. Province and provider sampling were significantly associated with completing triage. Province and triage type were significantly associated with receiving treatment. The odds of receiving treatment after Pap triage as compared to VIA was significantly lower (aOR: 0.05, 95% CI: 0.04-0.08, p < 0.001), and the relative proportion of women receiving treatment after Pap triage versus VIA was 0.29. CONCLUSIONS: Introduction of HPV testing resulted in a substantial number of women screened, and acceptance of self-sampling was high. Management of screen-positive women remained a challenge, particularly with Pap triage. Our results can inform other developing countries as they work to reach World Health Organization (WHO) elimination targets.

Age patterns of human papillomavirus infection as primary screening test for cervical cancer and subsequent triage with visual inspection in Honduras.

OBJECTIVE: To evaluate age patterns in human papillomavi-rus (HPV) prevalence and visual inspection with acetic acid (VIA) positivity among women participating in cervical cancerscreening in Honduras. MATERIALS AND METHODS: Data on the HPV status (careHPV) and subsequent VIA in HPV-positivewomen were retrieved from three provinces within the PublicHealth Sector. RESULTS: Between 2015 and 2018, 60 883 women aged 15-85 years were screened. HPV was detected in 15%, with variation by age, peaking at 20-24 years (27.8%) decreasing to 16% at 30-49 years. Differences in point age-specific HPV prevalence were observed between provinces,but with similar age pattern. VIA was positive in 24.5% of the women aged 30-44 year. CONCLUSIONS: The age pattern of the HPV prevalence supports starting HPV testing at age 30+. The low positivity of VIA in ages close to menopause suggest underdetection of cervical lesions in this age group.

OBJETIVO: Evaluar la prevalencia del virus del papilomahumano (VPH) y la positividad a la inspección visual con ácido acético (IVA) de cáncer cervicouterico, según edad en mujeres tamizadas en Honduras. MATERIAL Y MÉTODOS: Se extrajo información sobre la prueba de VPH (careHPV) y de IVA en tres provincias en el ámbito de la Atención Pública en Salud. RESULTADOS: Durante 2015-2018, 60 883 mujeresde 15-85 años fueron tamizadas, 15% fueron VPH positivas con valores máximos en mujeres de 20-24 años (27.8%),con una disminución a 16% entre 30-49 años. Se observaron diferencias mínimas entre provincias, con un patrón de edad similar. La IVA fue positiva en 24.5% en mujeres de 30-44 años, con una posterior disminución. CONCLUSIONES: La curva de prevalencia del VPH respalda el tamizar con VPH a los 30+ años. La baja positividad de la IVA en edades cercanas a la menopausia sugiere una subdetección de lesiones cervicales en este grupo.

Statistical Modeling for Quality Assurance of Human Papillomavirus DNA Batch Testing.

OBJECTIVES: Our objective was to simulate the distribution of human papillomavirus (HPV) DNA test results from a 96-well microplate assay to identify results that may be consistent with well-to-well contamination, enabling programs to apply specific quality assurance parameters. MATERIALS AND METHODS: For this modeling study, we designed an algorithm that generated the analysis population of 900,000 to simulate the results of 10,000 microplate assays, assuming discrete HPV prevalences of 12%, 13%, 14%, 15%, and 16%. Using binomial draws, the algorithm created a vector of results for each prevalence and reassembled them into 96-well matrices for results distribution analysis of the number of positive cells and number and size of cell clusters (≥2 positive cells horizontally or vertically adjacent) per matrix. RESULTS: For simulation conditions of 12% and 16% HPV prevalence, 95% of the matrices displayed the following characteristics: 5 to 17 and 8 to 22 total positive cells, 0 to 4 and 0 to 5 positive cell clusters, and largest cluster sizes of up to 5 and up to 6 positive cells, respectively. CONCLUSIONS: Our results suggest that screening programs in regions with an oncogenic HPV prevalence of 12% to 16% can expect 5 to 22 positive results per microplate in approximately 95% of assays and 0 to 5 positive results clusters with no cluster larger than 6 positive results. Results consistently outside of these ranges deviate from what is statistically expected and could be the result of well-to-well contamination. Our results provide guidance that laboratories can use to identify microplates suspicious for well-to-well contamination, enabling improved quality assurance.

The role of diet in children's exposure to organophosphate pesticides.

BACKGROUND: Studies suggest that some of the greatest exposure to OPs in children occurs in agricultural communities and various pathways of exposure including the take-home pathway, proximity to orchards, and diet have been explored. However, the importance of the dietary pathway of exposure for children in agricultural communities is not well understood. OBJECTIVES: Our goal was to ascertain whether there were associations between measures of OP exposure and apple juice, fruit, and vegetable consumption across growing seasons by children of farmworkers and non-farmworkers in a rural agricultural setting. METHODS: Study participants were children of farmworker (N=100) or non-farmworker (N=100) households from a longitudinal cohort study. Dietary intake of fruits and vegetables was assessed using a "5-A-Day" abbreviated food frequency questionnaire, and exposure to OPs was characterized using three urinary di-methyl and three di-ethyl metabolite measurements per child for each of three growing seasons. We used generalized estimating equations to examine data. RESULTS: Consumption frequency of fruits and vegetables was similar between children of farmworkers and non-farmworkers and across seasons. There were a few significant trends between dimethyl metabolites (DMAP) and fruit, vegetable or apple juice consumption; however, no clear pattern held across seasons or occupation. One difference was found in vegetable consumption during the harvest season, where the farmworker families showed a significant relationship between vegetable consumption and dimethyl metabolite levels (p=0.002). We also found a significant difference in this relationship between farmworkers and non-farmworkers (p=0.001). No significant trends between fruit and vegetable consumption and diethyl (DEAP) metabolites were found. CONCLUSIONS: Our study shows the importance of considering season and parents' occupation in understanding OP exposure routes among children in an agricultural community. The impact of these factors on dietary OP exposure requires a more thorough analysis of the availability and consumption of produce from different sources including farms using pesticides where parents worked.

A process evaluation of PRONTO simulation training for obstetric and neonatal emergency response teams in Guatemala.

BACKGROUND: Despite expanding access to institutional birth in Guatemala, maternal mortality remains largely unchanged over the last ten years. Enhancing the quality of emergency obstetric and neonatal care is one important strategy to decrease mortality. An innovative, low-tech, simulation-based team training program (PRONTO) aims to optimize care provided during obstetric and neonatal emergencies in low-resource settings. METHODS: We conducted PRONTO simulation training between July 2012 and December 2012 in 15 clinics in Alta Verapaz, Huehuetenango, San Marcos, and Quiche, Guatemala. These clinics received PRONTO as part of a larger pair-matched cluster randomized trial of a comprehensive intervention package. Training participants were obstetric and neonatal care providers that completed pre- and post- training assessments for the two PRONTO training modules, which evaluated knowledge of evidence-based practice and self-efficacy in obstetric and neonatal topics. Part of the training included a session for trained teams to establish strategic goals to improve clinical practice. We utilized a pre/post-test design to evaluate the impact of the course on both knowledge and self-efficacy with longitudinal fixed effects linear regression with robust standard errors. Pearson correlation coefficients were used to assess the correlation between knowledge and self-efficacy. Poisson regression was used to assess the association between the number of goals achieved and knowledge, self-efficacy, and identified facility-level factors. RESULTS: Knowledge and self-efficacy scores improved significantly in all areas of teaching. Scores were correlated for all topics overall at training completion. More than 60 % of goals set to improve clinic functioning and emergency care were achieved. No predictors of goal achievement were identified. CONCLUSIONS: PRONTO training is effective at improving provider knowledge and self-efficacy in training areas. Further research is needed to evaluate the impact of the training on provider use of evidence-based practices and on maternal and neonatal health outcomes. TRIAL REGISTRATION: NCT01653626.

Promoting cultural humility during labor and birth: putting theory into action during PRONTO obstetric and neonatal emergency training.

Maternal and neonatal mortality in Northern Guatemala, a region with a high percentage of indigenous people, is disproportionately high. Initiatives to improve quality of care at local health facilities equipped for births, and increasing the number of births attended at these facilities will help address this problem. PRONTO (Programa de Rescate Obstétrico y Neonatal: Tratamiento Óptimo y Oportuno) is a low-tech, high-fidelity, simulation-based, provider-to-provider training in the management of obstetric and neonatal emergencies. This program has been successfully tested and implemented in Mexico. PRONTO will now be implemented in Guatemala as part of an initiative to decrease maternal and perinatal mortality. Guatemalan health authorities have requested that the training include training on cultural humility and humanized birth. This article describes the process of curricular adaptation to satisfy this request. The PRONTO team adapted the existing program through 4 steps: (a) analysis of the problem and context through a review of qualitative data and stakeholder interviews, (b) literature review and adoption of a theoretical framework regarding cultural humility and adult learning, (c) adaptation of the curriculum and design of new activities and simulations, and (d) implementation of adapted and expanded curriculum and further refinement in response to participant response.

Recall Efforts Successfully Increase Follow-Up for Cervical Cancer Screening Among Women With Human Papillomavirus in Honduras.

Scaling up coverage of routine cervical screening in low-resource settings must be accompanied by efforts to retain women throughout the screening cascade and continuum of care, including adequate follow-up of abnormal results. The Scale-Up Project implemented human papillomavirus (HPV) testing for cervical cancer screening within public-sector health facilities in Honduras between 2015 and 2019. Women who were HPV-positive but did not have visually confirmed cervical lesions upon visual inspection with acetic acid (VIA-negative) were instructed to return to the health center after 1 year for repeat HPV testing. The current evaluation assessed the effectiveness of recall strategies to prompt women to return for retesting. Clinic staff placed reminder phone calls and followed up with short message service (SMS) or home visits, if needed. We summarized number of contacts, type of contacts, and time elapsed until return to the clinic, and used log-binomial regression to identify factors associated with return to the clinic. We identified 558 women who were initially HPV-positive VIA-negative from 8 clinics as needing repeat HPV testing 1 year later. Mean age was 43.2 years. Nearly all women (98.6%) were successfully contacted and 75.1% completed repeat HPV testing. The majority of contacts (65.4%) were phone calls, and nearly half of women who returned to the clinic (42.9%) did so after 1 contact. Mean days between contact and presentation at the clinic was 10.7 (standard deviation: 14.7). Women who required 3 or more contacts were 21% less likely to return for repeat HPV testing (prevalence ratio: 0.79; 95% confidence interval=0.69,0.90; P<.001) as compared to women who received only 1 contact. Reminder phone calls were highly successful at recalling women for HPV retesting in Honduras. This low-touch intervention should be included as part of standard follow-up to retain women throughout the continuum of cervical cancer screening and treatment.

What is needed now for successful scale-up of screening?

Effective screening for pre-cancerous lesions of the cervix is the only protective intervention that can be offered to women that have not had the opportunity to be vaccinated. Elimination goals are being developed so that by 2030, 70% of women aged 35-45 years should have been screened at least once in a lifetime and 90% of all detected lesions should have been treated. These goals focus on a substantial reduction of cervical cancer burden in low- and middle-income countries (LMICs). Scaling-up screening in these settings may be substantially improved by using self-sampling (SS), human papillomavirus (HPV) testing, and managing screened-positive women with accessible treatment. The implementation of these tools requires minimal health information data for traceability, provider training, community education, operational management and quality control. Cost-effective algorithms tailored to country needs can greatly impact the burden of disease in a limited number of years.

Scaling up proven innovative cervical cancer screening strategies: Challenges and opportunities in implementation at the population level in low- and lower-middle-income countries.

The problem of cervical cancer in low- and lower-middle-income countries (LLMICs) is both urgent and important, and calls for governments to move beyond pilot testing to population-based screening approaches as quickly as possible. Experiences from Zambia, Bangladesh, Guatemala, Honduras, and Nicaragua, where scale-up of evidence-based screening strategies is taking place, may help other countries plan for large-scale implementation. These countries selected screening modalities recommended by the WHO that are within budgetary constraints, improve access for women, and reduce health system bottlenecks. In addition, some common elements such as political will and government investment have facilitated action in these diverse settings. There are several challenges for continued scale-up in these countries, including maintaining trained personnel, overcoming limited follow-up and treatment capacity, and implementing quality assurance measures. Countries considering scale-up should assess their readiness and conduct careful planning, taking into consideration potential obstacles. International organizations can catalyze action by helping governments overcome initial barriers to scale-up.

Cost-effectiveness of HPV-based cervical cancer screening in the public health system in Nicaragua.

OBJECTIVES: To evaluate the cost-effectiveness of human papillomavirus (HPV) DNA testing (versus Papanicolaou (Pap)-based screening) for cervical cancer screening in Nicaragua. DESIGN: A previously developed Monte Carlo simulation model of the natural history of HPV infection and cervical cancer was calibrated to epidemiological data from Nicaragua. Cost data inputs were derived using a micro-costing approach in Carazo, Chontales and Chinandega departments; test performance data were from a demonstration project in Masaya department. SETTING: Nicaragua's public health sector facilities. PARTICIPANTS: Women aged 30-59 years. INTERVENTIONS: Screening strategies included (1) Pap testing every 3 years, with referral to colposcopy for women with an atypical squamous cells of undetermined significance or worse result ('Pap'); (2) HPV testing every 5 years, with referral to cryotherapy for HPV-positive eligible women (HPV cryotherapy or 'HPV-Cryo'); (3) HPV testing every 5 years, with referral to triage with visual inspection with acetic acid (VIA) for HPV-positive women ('HPV-VIA'); and (4) HPV testing every 5 years, with referral to Pap testing for HPV-positive women ('HPV-Pap'). OUTCOME MEASURES: Reduction in lifetime risk of cancer and incremental cost-effectiveness ratios (ICER; 2015 US$ per year of life saved (YLS)). RESULTS: HPV-based screening strategies were more effective than Pap testing. HPV-Cryo was the least costly and most effective strategy, reducing lifetime cancer risk by 29.5% and outperforming HPV-VIA, HPV-Pap and Pap only, which reduced cancer risk by 19.4%, 12.2% and 10.8%, respectively. With an ICER of US$320/YLS, HPV-Cryo every 5 years would be very cost-effective using a threshold based on Nicaragua's per capita gross domestic product of US$2090. Findings were robust across sensitivity analyses on test performance, coverage, compliance and cost parameters. CONCLUSIONS: HPV testing is very cost-effective compared with Pap testing in Nicaragua, due to higher test sensitivity and the relatively lower number of visits required. Increasing compliance with recommended follow-up will further improve the health benefits and value for public health dollars.

Implementation of HPV testing in Latin America.

Cervical cancer is one of the leading killers among women in Latin America, a region where most countries have not been successful in implementing population-level cytology-based screening programs. This disease is caused by persistent infection with oncogenic HPV; in recent years, more HPV tests have become available and prices have dropped significantly, making it possible for countries to adopt these technologies. Pilot programs that took place in Nicaragua, Mexico, and Argentina showed a high level of efficacy in detecting precancerous cervical lesions and good feasibility and acceptance of self-sampling. El Salvador, Guatemala, Honduras, and Nicaragua are beginning to institutionalize HPV testing at the population level. The experience from the different countries has created rich information about the barriers and requirements for implementing HPV screening at large scale in these resource-constrained countries. There are several challenges for implementation, including a need to update screening guidelines, strengthen treatment capacity, and develop a comprehensive quality assurance plan for the HPV testing. At the same time, there are several opportunities in Latin America that make the process more feasible and faster than in other regions of the world: most Latin American countries already have screening programs funded by their national governments, several countries in the region are already implementing HPV testing, and there is a regional pooled procurement mechanism that could facilitate the purchase of HPV tests at an accessible price. We envision that most countries in the region will include HPV testing in their national program within the next three to five years.

Impact of a low-technology simulation-based obstetric and newborn care training scheme on non-emergency delivery practices in Guatemala.

OBJECTIVE: To assess the effect of a low-technology simulation-based training scheme for obstetric and perinatal emergency management (PRONTO; Programa de Rescate Obstétrico y Neonatal: Tratamiento Óptimo y Oportuno) on non-emergency delivery practices at primary level clinics in Guatemala. METHODS: A paired cross-sectional birth observation study was conducted with a convenience sample of 18 clinics (nine pairs of intervention and control clinics) from June 28 to August 7, 2013. Outcomes included implementation of practices known to decrease maternal and/or neonatal mortality and improve patient care. RESULTS: Overall, 25 and 17 births occurred in intervention and control clinics, respectively. Active management of the third stage of labor was appropriately performed by 20 (83%) of 24 intervention teams versus 7 (50%) of 14 control teams (P=0.015). Intervention teams implemented more practices to decrease neonatal mortality than did control teams (P<0.001). Intervention teams ensured patient privacy in 23 (92%) of 25 births versus 11 (65%) of 17 births for control teams (P=0.014). All 15 applicable intervention teams kept patients informed versus 6 (55%) of 11 control teams (P=0.001). Differences were also noted in teamwork; in particular, skill-based tools were used more often at intervention sites than control sites (P=0.012). CONCLUSION: Use of PRONTO enhanced non-emergency delivery care by increasing evidence-based practice, patient-centered care, and teamwork.

Age patterns of human papillomavirus infection as primary screening test for cervical cancer and subsequent triage with visual inspection in Honduras / Patrones de edad de infección por el virus del papiloma humano como prueba primaria en el tamizaje de cáncer de cuello uterino y triaje posterior con inspección visual en Honduras

Abstract Objective: To evaluate age patterns in human papillomavirus (HPV) prevalence and visual inspection with acetic acid (VIA) positivity among women participating in cervical cancer screening in Honduras. Materials and methods: Data on the HPV status (careHPV) and subsequent VIA in HPV-positive women were retrieved from three provinces within the Public Health Sector. Results: Between 2015 and 2018, 60 883 women aged 15-85 years were screened. HPV was detected in 15%, with variation by age, peaking at 20-24 years (27.8%) decreasing to 16% at 30-49 years. Differences in point age-specific HPV prevalence were observed between provinces, but with similar age pattern. VIA was positive in 24.5% of the women aged 30-44 years. Conclusions: The age pattern of the HPV prevalence supports starting HPV testing at age 30+. The low positivity of VIA in ages close to menopause suggest underdetection of cervical lesions in this age group.

Resumen Objetivo: Evaluar la prevalencia del virus del papiloma humano (VPH) y la positividad a la inspección visual con ácido acético (IVA) de cáncer cervicouterico, según edad en mujeres tamizadas en Honduras. Material y métodos: Se extrajo información sobre la prueba de VPH (careHPV) y de IVA en tres provincias en el ámbito de la Atención Pública en Salud. Resultados: Durante 2015-2018, 60 883 mujeres de 15-85 años fueron tamizadas, 15% fueron VPH positivas con valores máximos en mujeres de 20-24 años (27.8%), con una disminución a 16% entre 30-49 años. Se observaron diferencias mínimas entre provincias, con un patrón de edad similar. La IVA fue positiva en 24.5% en mujeres de 30-44 años, con una posterior disminución. Conclusiones: La curva de prevalencia del VPH respalda el tamizar con VPH a los 30+ años. La baja positividad de la IVA en edades cercanas a la menopausia sugiere una subdetección de lesiones cervicales en este grupo.