The CryoPop study: Screening for high-grade cervical dysplasia in Karnataka, India.

OBJECTIVE: To describe our experience of screening with visual inspection with acetic acid (VIA) and colposcopy to identify women with high-grade precancerous cervical lesions who were candidates for cryotherapy. Women were screened to determine eligibility for a clinical trial testing the safety and efficacy of a new, simple and inexpensive cryotherapy device (CryoPop®) targeted for use in low and middle-income countries (LMICs). DESIGN: Prospective cohort study. SETTING: Primary and urban health centres in Belagavi, Hubballi and Vijayapur, India. POPULATION: Women in the age-group 30-49 years, premenopausal, with no prior hysterectomy and no known HIV infection were eligible for screening. METHODS: Visual inspection with acetic acid was performed on eligible women following informed consent. VIA-positive women were referred for colposcopy and biopsy. Biopsies were read by two pathologists independently, with a third pathologist acting as tie-breaker if needed. MAIN OUTCOME MEASURES: The primary outcome measures were the number/proportion of women screening positive by VIA and the number/proportion of those women screening VIA-positive found to have high-grade cervical lesions on biopsy (cervical intraepithelial neoplasia 2/3 [CIN 2/3]). Demographic variables were compared between women who screened VIA-positive and those who screened VIA-negative; a separate comparison of demographic and limited reproductive variables was performed between women who had CIN 2/3 on biopsy and those without CIN 2/3 on biopsy. Chi-square or Fisher's exact tests for categorical data and t-tests or analysis of variance for numeric data were used with all tests two-sided and performed at an alpha 0.05 level of statistical significance. RESULTS: A total of 9130 women were screened with VIA between 4 July 2020 and 31 March 2021. The mean age of all women screened was 37 years (standard deviation = 5.6 years) with 6073 of the women (66.5%) in the 30-39 year range. Only 1% of women reported prior cervical cancer screening. A total of 501 women (5.5%) were VIA-positive; of these, 401 women underwent colposcopy. Of those who had colposcopy, 17 (4.2%) had high-grade lesions on biopsy, an additional 164 (40.9%) had low-grade cervical lesions on biopsy or endocervical curettage and one woman (0.2%) was found to have invasive cancer. VIA-positive women were younger and had higher levels of education and income; however, women who were VIA-positive and found to have CIN 2/3 were older, were more likely to be housewives and had higher household income than those without CIN 2/3. CONCLUSION: Despite the COVID-19 pandemic, over 9100 women were screened with VIA for precancerous lesions. However, only 17 (4.2%) were found to have biopsy-proven high-grade cervical lesions, underscoring the subjective performance of VIA as a screening method. Given that this is significantly lower than rates reported in the literature, it is possible that the prevalence of high-grade lesions in this population was impacted by screening a younger and more rural population. This study demonstrates that screening is feasible in an organised fashion and can be scaled up rapidly. However, while inexpensive and allowing for same-day treatment, VIA may be too subjective and have insufficient accuracy clearly to identify lesions requiring treatment, particularly in low-prevalence and low-risk populations, calling into question its overall cost-effectiveness.

Safety and efficacy of the new CryoPop® cryotherapy device for cervical dysplasia in low- and middle-income countries: study protocol for a multicenter open-label non-inferiority clinical trial with historical controls.

BACKGROUND: Cervical cancer is the fourth most common cancer in the world, affecting mainly women residing in low- and middle-income countries. Progression from a pre-invasive phase to that of an invasive phase generally takes years and provides a window of opportunity to screen for and treat precancerous lesions. METHODS: This study is being conducted at four sites in north Karnataka, India. Community sensitization activities have been organized in the study areas to create awareness among stakeholders, including elected representatives, physicians, health care workers, and potential participants. Organized community based as well as hospital-based screening is being conducted using visual inspection with acetic acid (VIA). Screen positive women are referred to respective study hospitals for colposcopy and directed biopsy. Participants with confirmed high-grade cervical dysplasia (high-grade squamous intraepithelial lesions or HSIL) who fit all other eligibility criteria will be recruited to the study and will receive cryotherapy using CryoPop®, an innovative new cryotherapy device. DISCUSSION: There is a need to develop an inexpensive, simple, and effective cryotherapy device for use by frontline health care providers at locations where screening and timely treatment can be given, accelerating access to cervical cancer prevention services and minimizing loss to follow-up of women with precancerous lesions who need treatment. TRIAL REGISTRATION: Clinical Trial Registry - India CTRI/2019/01/017289 ClinicalTrials.Gov number NCT04154644 . Registered on November 6, 2019.

Health facility capacity to provide postabortion care in Afghanistan: a cross-sectional study.

BACKGROUND: Afghanistan has one of the highest burdens of maternal mortality in the world, estimated at 638 deaths per 100,000 live births in 2017. Infections, obstetric hemorrhage, and unsafe abortion are the three leading causes of maternal death. Contraceptive prevalence rate has fluctuated between 10 and 20% since 2006. The 2016 Afghanistan National Maternal and Newborn Health Quality of Care Assessment evaluated facility readiness to provide quality routine and emergency obstetric and newborn care, including postabortion care services. METHODS: Accessible public health facilities with at least five births per day (n = 77), a nationally representative sample of public health facilities with fewer than five births per day (n = 149), and 20 purposively selected private health facilities were assessed. Assessment components examining postabortion care included a facility inventory and record review tool to verify drug, supply, equipment, and facility record availability, and an interview tool to collect information on skilled birth attendants' knowledge and perceptions. RESULTS: Most facilities had supplies, equipment, and drugs to manage postabortion care, including family planning counseling and services provision. At public facilities, 36% of skilled birth attendants asked to name essential actions to address abortion complications mentioned manual vacuum aspiration (23% at private facilities); fewer than one-quarter mentioned counseling. When asked what information should be given to postabortion clients, 73% described family planning counseling need (70% at private facilities). Nearly all high-volume public health facilities with an average of five or more births per day and less than 5% of low volume public health facilities with an average of 0-4 deliveries per day reported removal of retained products of conception in the past 3 months. Among the 77 high volume facilities assessed, 58 (75%) reported using misoprostol for removal of retained products of conception, 59 (77%) reported using manual vacuum aspiration, and 67 (87%) reported using dilation and curettage. CONCLUSIONS: This study provides evidence that there is room for improvement in postabortion care services provision in Afghanistan health facilities including post abortion family planning. Access to high-quality postabortion care needs additional investments to improve providers' knowledge and practice, availability of supplies and equipment.

Afghanistan has one of the highest burdens of maternal mortality in the world. Infections, bleeding around childbirth, and unsafe abortion are the three leading causes of mortality in the country. The uptake of contraceptives is low, and only one-fifth of married women use contraceptives. A National Maternal and Newborn Health Quality of Care Assessment was conducted in 2016 at a selected number of public and private health facilities (n = 226; n = 20) to evaluate health facilities' capacity to provide postabortion care, and skilled birth attendants' knowledge and perceptions with regard to such care. Postabortion care is an essential package of services to make women survive complications of miscarriage and abortion and reduce unplanned pregnancies by providing postabortion family planning counseling and services, community empowerment, and mobilization. The result of this study showed that most facilities had supplies, equipment, and drugs to give postabortion care, including family planning services provision. However, there are gaps in birth attendants' knowledge and their capacity to deliver high-quality postabortion care services at public and private facilities. This study provides evidence that there is room for improvement in postabortion care services provision at health facilities in Afghanistan. Access to high-quality postabortion care needs additional investments to improve providers' knowledge and practice, and availability of supplies.

Reinvigorating postpartum intrauterine contraceptive device use in Pakistan: an observational assessment of competency-based training of health providers using low-cost simulation models.

BACKGROUND: Improved training approaches have the potential to overcome barriers to the use of postpartum intrauterine devices (PPIUDs) in Pakistan, including a shortage of female providers who are able to insert the device. This study assessed the effectiveness and acceptability of a competency-based onsite training approach that employed a newly developed anatomic model (the Mama-U) to train doctors and midwives on postpartum family planning (PPFP) and the insertion of PPIUDs. METHODS: An observational, mixed methods study conducted training evaluations and knowledge and skills assessments with 11 trainers and 88 doctors and midwives who participated in eight PPIUD training sessions. Two months later, follow-up interviews and clinical assessments were conducted with 20 providers, and interviews and a focus group discussion were conducted with 85 married women who received a PPIUD from a trained provider. RESULTS: The training significantly improved provider knowledge (p < 0.001), and follow-up assessments showed that clinical skills were retained for at least two months post-training. After training, 81.8% of providers were confident in their ability to provide PPIUD services, and midwives and doctors had similar PPIUD insertion skills. However, midwives were more likely than doctors to meet all 10 key requirements during PPIUD counseling sessions (63.9% versus 13.3%, p = 0.004). Providers found the Mama-U model to be a useful tool for client counseling as well as training and skills practice, and clients agreed. Trainers identified the low cost, light weight, and portability of the Mama-U model as advantages over the conventional training model and noted that its abstract shape reduced embarrassment among trainers, providers, and clients. CONCLUSIONS: Competency-based training with the Mama-U model can improve the quality of PPIUD counseling and PPIUD insertion services and has the potential to extend PPFP/PPIUD service delivery to midwives working in rural Pakistan. The portable, low-cost Mama-U permits onsite, on-the-job PPIUD insertion training that is tailored to the local setting; it is also well suited for the continuing practice that providers need to maintain their skills. Further research is needed to confirm the usefulness and cost-effectiveness of the Mama-U at scale and in other settings.

World Health Organization Guidelines for treatment of cervical intraepithelial neoplasia 2-3 and screen-and-treat strategies to prevent cervical cancer.

BACKGROUND: It is estimated that 1%-2% of women develop cervical intraepithelial neoplasia grade 2-3 (CIN 2-3) annually worldwide. The prevalence among women living with HIV is higher, at 10%. If left untreated, CIN 2-3 can progress to cervical cancer. WHO has previously published guidelines for strategies to screen and treat precancerous cervical lesions and for treatment of histologically confirmed CIN 2-3. METHODS: Guidelines were developed using the WHO Handbook for Guideline Development and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. A multidisciplinary guideline panel was created. Systematic reviews of randomized controlled trials and observational studies were conducted. Evidence tables and Evidence to Recommendations Tables were prepared and presented to the panel. RESULTS: There are nine recommendations for screen-and-treat strategies to prevent cervical cancer, including the HPV test, cytology, and visual inspection with acetic acid. There are seven for treatment of CIN with cryotherapy, loop electrosurgical excision procedure, and cold knife conization. CONCLUSION: Recommendations have been produced on the basis of the best available evidence. However, high-quality evidence was not available. Such evidence is needed, in particular for screen-and-treat strategies that are relevant to low- and middle-income countries.

Evaluation of Cervical Cancer Screening Programs in Côte d'Ivoire, Guyana, and Tanzania: Effect of HIV Status.

BACKGROUND: HIV infection increases a woman's risk for cervical cancer, and cervical cancer incidence and mortality rates are higher in countries with high HIV prevalence and limited resources for screening. Visual inspection with acetic acid (VIA) allows screening and treatment of cervical lesions in a single-visit approach (SVA), but data on its performance in HIV-infected women are limited. This study's objective was to examine cervical cancer screening using VIA/SVA in programs serving HIV-infected women. METHODS: A VIA/SVA program with cryotherapy for VIA-positive lesions was implemented in Côte d'Ivoire, Guyana, and Tanzania from 2009 to 2012. The effect of HIV status on VIA positivity and on presence of cryotherapy-eligible lesions was examined using a cross-sectional study design, with Chi-square tests for comparisons and constructed multivariate logistic regression models. A P-value of < 0.05 was significant. FINDINGS: VIA was performed on 34,921 women, 10% (3,580) were VIA positive; 2,508 (85%) eligible women received cryotherapy during the same visit; only 234 (52%) of those who postponed returned for treatment; 622 (17%) VIA-positive women had lesions too large to be treated with cryotherapy and were referred for excisional treatment. In multivariate analysis-controlling for HIV status, location of the screening clinic, facility location, facility type, and country-compared to HIV-uninfected/unknown women, HIV-infected women had higher odds of being VIA positive (OR 1.95, 95% CI 1.76, 2.16, P<0.0001) and of having large lesions requiring referral (OR 1.93, 95% CI 1.49, 2.51, P< 0.0001). Minor treatment complications occurred in 19 of 3,032 (0.63%) women; none required further intervention. CONCLUSIONS: This study found that compared to HIV-uninfected/unknown women, HIV-infected women had nearly twice the odds of being VIA-positive and to require referral for large lesions. SVA was safe and resulted in significant reductions in loss to follow-up. There is increased need for excisional treatment in countries with high HIV prevalence.

Integrating HIV testing into cervical cancer screening in Tanzania: an analysis of routine service delivery statistics.

BACKGROUND: While the lifetime risk of developing cervical cancer (CaCx) and acquiring HIV is high for women in Tanzania, most women have not tested for HIV in the past year and most have never been screened for CaCx. Good management of both diseases, which have a synergistic relationship, requires integrated screening, prevention, and treatment services. The aim of this analysis is to assess the acceptability, feasibility and effectiveness of integrating HIV testing into CaCx prevention services in Tanzania, so as to inform scale-up strategies. METHODS: We analysed 2010-2013 service delivery data from 21 government health facilities in four regions of the country, to examine integration of HIV testing within newly introduced CaCx screening and treatment services, located in the reproductive and child health (RCH) section of the facility. Analysis included the proportion of clients offered and accepting the HIV test, reasons why testing was not offered or was declined, and HIV status of CaCx screening clients. RESULTS: A total of 24,966 women were screened for CaCx; of these, approximately one-quarter (26%) were referred in from HIV care and treatment clinics. Among the women of unknown HIV status (n = 18,539), 60% were offered an HIV test. The proportion of women offered an HIV test varied over time, but showed a trend of decline as the program expanded. Unavailability of HIV test kits at the facility was the most common reason for a CaCx screening client not to be offered an HIV test (71% of 6,321 cases). Almost all women offered (94%) accepted testing, and 5% of those tested (582 women) learned for the first time that they were HIV-positive. CONCLUSION: Integrating HIV testing into CaCx screening services was highly acceptable to clients and was an effective means of reaching HIV-positive women who did not know their status; effectiveness was limited, however, by shortages of HIV test kits at facilities. Integration of HIV testing into CaCx screening services should be prioritized in HIV-endemic settings, but more work is needed to eliminate logistical barriers. The coverage of CaCx screening among HIV care and treatment-enrolled women in Tanzania may be low and should be examined.

Evaluation of a 5-year cervical cancer prevention project in Indonesia: opportunities, issues, and challenges.

AIM: The Cervical and Breast Cancer Prevention (CECAP) Project sought to develop a national model for cervical cancer prevention in Indonesia based on visual inspection with acetic acid (VIA) to detect abnormal changes in the cervix. The purpose of this study was to evaluate a pilot project introducing VIA and cryotherapy in Indonesia and to identify lessons learned that could be applied to the national scale-up of cervical cancer prevention services. MATERIAL AND METHODS: Fifty-four months (July 2007 to December 2011) of service records at 17 health centers were abstracted and analyzed. The data were used to calculate the proportion of all women aged 30-50 who received VIA screening, the VIA-positive rate, the treatment rate, and the interval between screening and treatment. RESULTS: The 45 050 women screened during the project included 24.4% of the total female population in the target age group in the catchment area. Throughout the 5-year project, 83.1% of VIA-positive women sought cryotherapy. During the last 18 months of the project, after data collection tools were revised to more accurately reflect when cryotherapy was received, 13% of women were treated on the same day that they were screened. Among the 74% of women treated within 1 month of screening, the mean interval between screening and treatment was 7.2 days. CONCLUSION: As cervical cancer prevention services are scaled up throughout Indonesia, changes in the service delivery model and program management are needed to increase screening coverage, promote a single-visit approach, and ensure the quality of services.

Influencing women's actions on cervical cancer screening and treatment in Karawang District, Indonesia.

INTRODUCTION: The impact of cervical cancer prevention programs depends on persuading women to go for screening and, if needed, treatment. As part of an evaluation of a pilot project in Indonesia, qualitative research was conducted to explore the factors that influence women's decisions regarding screening and treatment and to generate practical recommendations to increase service coverage and reduce loss to follow up. METHODS: Research was conducted at 7 of the 17 public health centers in Karawang District that implemented the pilot project. Interviews and focus group discussions were held with 20 women, 20 husbands, 10 doctors, 18 midwives, 3 district health officials, and 16 advocacy team members. RESULTS: Free services and mobile outreach events encouraged women to go for screening, along with promotional efforts by community health workers, advocacy teams, and the mass media. Knowledge and perceptions were the most important barriers to screening: women were not aware of cervical cancer risks, did not know the disease was treatable, and were fatalistic. Factors facilitating treatment were social support from husbands, relatives, and friends and the encouragement and role modeling of health workers. Barriers to prompt treatment included limited access to services and the requirement for husband's consent for cryotherapy. CONCLUSION: As cervical cancer prevention services are scaled up throughout Indonesia, the findings suggest three strategies to expand screening coverage and ensure prompt treatment: strengthening community mobilization and advocacy activities, modifying the service delivery model to encourage a single visit approach to screening and treatment, and working to gain men's support.

Cervical cancer screening using visual inspection with acetic acid: operational experiences from Ghana and Thailand.

Thailand in 2000 and Ghana in 2001 initiated cervical cancer prevention programmes using a single-visit approach with visual inspection with acetic acid (VIA) with cryotherapy for pre-cancerous lesions. This service was integrated into existing reproductive health services, provided by trained nurses. The providers maintained a high level of competence and performance, including after the withdrawal of external funding. In Ghana, independent co-assessments revealed a high level of agreement in diagnosis between providers and a Master Trainer. In Thailand, high quality performance was associated with quality assurance mechanisms such as peer feedback and review of charts and service statistics. Provider performance was maintained at a high level in both countries: an average of 74% of providers from both countries met 85% or more of performance standards. The successful transition from a demonstration project to a national programme in Thailand was dependent on a strong commitment from government health bodies and health professionals. In contrast, the lack of health infrastructure and political will has prevented scale-up to a national programme in Ghana. However, this study shows that a single-visit approach with VIA and cryotherapy is programmatically feasible and sustainable and should be considered in national investments to control cervical cancer.