Acting on the call for cervical cancer elimination: Planning tools for low- and middle- income countries to increase the coverage and effectiveness of screening and treatment.

INTRODUCTION: Accessible planning tools tailored for low-and middle-income countries can assist decision makers in comparing implementation of different cervical cancer screening approaches and treatment delivery scenarios in settings with high cervical cancer burden. METHODS: The Cervical Precancer Planning Tool (CPPT) was developed by PATH for users to explore and compare the accuracy of screening approaches, what treatment equipment to procure, and how best to deploy treatment equipment in a given country. The CPPT compares four screening approaches: 1) visual inspection with acetic acid (VIA), 2) HPV testing, 3) HPV testing followed by a VIA triage, and 4) HPV testing followed by an enhanced triage test. Accuracy of screening outcomes (e.g., true positives, false positives) is based on published sensitivity and specificity of tests to detect cervical precancerous lesions. The CPPT compares five scenarios for deploying ablative treatment equipment: 1) cervical precancer equipment at every location a woman is screened (single visit approach), 2) equipment only at a hospital level, 3) a single unit of equipment in each district, 4) allowing two districts to share a single unit of equipment, and 5) equipment placed at select district hospitals paired with mobile outreach. Users can customize the CPPT by adjusting pre-populated baseline values and assumptions, including population estimates, screening age range, screening frequency, HPV and HIV prevalence, supply costs, and health facility details. RESULTS: The CPPT generates data tables and graphs that compare the results of implementing each of the four screening and five treatment scenarios disaggregated by HIV status. Outputs include the number and outcomes of women screened, cost of each screening approach, provider time and cost saved by implementing self-sampling for HPV testing, number of women treated, treatment equipment needed by type, and the financial and economic costs for each equipment deployment scenario. CONCLUSION: The CPPT provides practical information and data to compare tradeoffs of patient access and screening accuracy as well as efficient utilization of equipment, skilled personnel, and financial resources. Country decision makers can use outputs from the CPPT to guide the scale-up of cervical cancer screening and treatment while optimizing limited resources.

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.

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.

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.

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.

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.

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.

Retest and treat: a review of national HIV retesting guidelines to inform elimination of mother-to-child HIV transmission (EMTCT) efforts.

INTRODUCTION: High maternal HIV incidence contributes substantially to mother-to-child HIV transmission (MTCT) in some settings. Since 2006, HIV retesting during the third trimester and breastfeeding has been recommended by the World Health Organization in higher prevalence (≥5%) settings to reduce MTCT. However, many countries lack clarity on when and how often to retest pregnant and postpartum women to optimize resources and service delivery. We reviewed and characterized national guidelines on maternal retesting based on timing and frequency. METHODS: We identified 52 countries to represent variations in HIV prevalence, geography, and MTCT priority and searched available national MTCT, HIV testing and HIV treatment policies published between 2007 and 2017 for recommendations on retesting during pregnancy, labour/delivery and postpartum. Recommended retesting frequency and timing was extracted. Country HIV prevalence was classified as: very low (<1%), low (1% to 5%), intermediate (>5 to <15%) and high (≥15%). Women with unknown HIV status at delivery/postpartum were included in retesting guidelines. RESULTS AND DISCUSSION: Overall, policies from 49 countries were identified; 51% from 2015 or later and most (n = 25) were from Africa. Four countries were high HIV prevalence, seven intermediate, sixteen low and twenty-two very low. Most (n = 31) had guidance on universal voluntary opt-out HIV testing at the first antenatal care (ANC) visit. Beyond the first ANC visit, the majority (78%, n = 38) had guidance on retesting; 22 recommended retesting all women with unknown/negative status, five only if unknown HIV status, three in pregnancy based on risk and eight combining these approaches. Retesting was universally recommended during pregnancy, labour/delivery, and postpartum for all high prevalence settings and four of seven intermediate prevalence settings. Five UNAIDS priority countries for EMTCT with low/very low HIV prevalence, but high/intermediate MTCT, had no guidance on retesting. CONCLUSIONS: Retesting guidelines for pregnant and postpartum women were ubiquitous in high prevalence countries and defined in some intermediate prevalence countries, but absent in some low HIV prevalence countries with high MTCT. Countries may require additional guidance on how to optimize maternal HIV testing and whether to prioritize retesting efforts or discontinue universal retesting based on HIV incidence. Research is needed to assess country-level guideline implementation and impact.

Feasibility and acceptability of HIV self-testing among pre-exposure prophylaxis users in Kenya.

INTRODUCTION: HIV testing is key to the delivery of pre-exposure prophylaxis (PrEP): testing HIV-uninfected at-risk persons is the first step for PrEP initiation and ongoing HIV testing is an essential part of PrEP delivery. Thus, novel and cost-effective HIV-testing approaches to streamline delivery of PrEP are urgently needed. Within a demonstration project of PrEP for HIV prevention among high-risk HIV serodiscordant couples in Kenya (the Partners Demonstration Project), we conducted a pilot evaluation of HIV self-testing. METHODS: Clinic visits were scheduled quarterly and included in-clinic HIV testing using fingerstick rapid HIV tests and refills of PrEP prescriptions. HIV oral fluid self-test kits were provided for participants to use in the two-month interval between scheduled quarterly clinic visits. Acceptability of HIV self-testing was assessed using both quantitative and qualitative methods. RESULTS: We found that 222 of 226 (98%) HIV-uninfected persons who were offered accepted self-testing. Nearly all (96.8%) reported that using the self-testing kit was easy. More than half (54.5%) reportedly did not share the HIV results from self-testing with anyone and almost all (98.7%) the participants did not share the HIV self-testing kits with anyone. Many participants reported that HIV self-testing was empowering and reduced anxiety associated with waiting between clinic HIV tests. CONCLUSION: HIV self-testing was highly acceptable and may therefore be a feasible strategy to efficiently permit routine HIV testing between PrEP refills.

Tenofovir-based oral preexposure prophylaxis prevents HIV infection among women.

PURPOSE OF REVIEW: Despite tremendous promise as a female-controlled HIV prevention strategy, implementation of preexposure prophylaxis (PrEP) among women has been limited, in part because of disparate efficacy results from randomized trials in this population. This review synthesizes existing evidence regarding PrEP efficacy for preventing HIV infection in women and considerations for delivering PrEP to women. RECENT FINDINGS: In three efficacy trials, conducted among men and women, tenofovir-based oral PrEP reduced HIV acquisition in subgroups of women by 49-79% in intent-to-treat analyses, and by >85% when accounting for PrEP adherence. Two trials did not demonstrate an HIV prevention benefit from PrEP in women, but substantial evidence indicates those results were compromised by very low adherence to the study medication. Qualitative research has identified risk perception, stigma, and aspects of clinical trial participation as influencing adherence to study medication. Pharmacokinetic studies provide supporting evidence that PrEP offers HIV protection in women who are adherent to the medication. SUMMARY: Tenofovir-based daily oral PrEP prevents HIV acquisition in women. Offering PrEP as an HIV prevention option for women at high risk of HIV acquisition is a public health imperative and opportunities to evaluate implementation strategies for PrEP for women are needed.