Cost-effectiveness of single-visit cervical cancer screening in KwaZulu-Natal, South Africa: a model-based analysis accounting for the HIV epidemic

Introduction Women living with human immunodeficiency virus (WLHIV) face elevated risks of human papillomavirus (HPV) acquisition and cervical cancer (CC). Coverage of CC screening and treatment remains low in low-and-middle-income settings, reflecting resource challenges and loss to follow-up with current strategies. We estimated the health and economic impact of alternative scalable CC screening strategies in KwaZulu-Natal, South Africa, a region with high burden of CC and HIV. Methods We parameterized a dynamic compartmental model of HPV and HIV transmission and CC natural history to KwaZulu-Natal. Over 100 years, we simulated the status quo of a multi-visit screening and treatment strategy with cytology and colposcopy triage (South African standard of care) and six single-visit comparator scenarios with varying: 1) screening strategy (HPV DNA testing alone, with genotyping, or with automated visual evaluation triage, a new high-performance technology), 2) screening frequency (once-per-lifetime for all women, or repeated every 5 years for WLHIV and twice for women without HIV), and 3) loss to follow-up for treatment. Using the Ministry of Health perspective, we estimated costs associated with HPV vaccination, screening, and pre-cancer, CC, and HIV treatment. We quantified CC cases, deaths, and disability-adjusted life-years (DALYs) averted for each scenario. We discounted costs (2022 US dollars) and outcomes at 3% annually and calculated incremental cost-effectiveness ratios (ICERs). Results We projected 69,294 new CC cases and 43,950 CC-related deaths in the status quo scenario. HPV DNA testing achieved the greatest improvement in health outcomes, averting 9.4% of cases and 9.0% of deaths with one-time screening and 37.1% and 35.1%, respectively, with repeat screening. Compared to the cost of the status quo ($12.79 billion), repeat screening using HPV DNA genotyping had the greatest increase in costs. Repeat screening with HPV DNA testing was the most effective strategy below the willingness to pay threshold (ICER:$3,194/DALY averted). One-time screening with HPV DNA testing was also an efficient strategy (ICER: $1,398/DALY averted). Conclusions Repeat single-visit screening with HPV DNA testing was the optimal strategy simulated. Single-visit strategies with increased frequency for WLHIV may be cost-effective in KwaZulu-Natal and similar settings with high HIV and HPV prevalence

Sustaining a “culture of silence” in the neonatal intensive care unit during nonemergency situations: A grounded theory on ensuring adherence to behavioral modification to reduce noise levels

The aim of this study was to generate a substantive theory explaining how the staff in a resource-limited neonatal intensive care unit (NICU) of a developing nation manage to ensure adherence to behavioral modification components of a noise reduction protocol (NsRP) during nonemergency situations. The study was conducted after implementation of an NsRP in a level III NICU of south India. The normal routine of the NICU is highly dynamic because of various categories of staff conducting clinical rounds followed by care-giving activities. This is unpredictably interspersed with very noisy emergency management of neonates who suddenly fall sick. In-depth interviews were conducted with 36 staff members of the NICU (20 staff nurses, six nursing aides, and 10 physicians). Group discussions were conducted with 20 staff nurses and six nursing aides. Data analysis was done in line with the reformulated grounded theory approach, which was based on inductive examination of textual information. The results of the analysis showed that the main concern was to ensure adherence to behavioral modification components of the NsRP. This was addressed by using strategies to “sustain a culture of silence in NICU during nonemergency situations” (core category). The main strategies employed were building awareness momentum, causing awareness percolation, developing a sense of ownership, expansion of caring practices, evolution of adherence, and displaying performance indicators. The “culture of silence” reconditions the existing staff and conditions new staff members joining the NICU. During emergency situations, a “noisy culture” prevailed because of pragmatic neglect of behavioral modification when life support overrode all other concerns. In addition to this, the process of operant conditioning should be formally conducted once every 18 months. The results of this study may be adapted to create similar strategies and establish context specific NsRPs in NICUs with resource constraints

Mathematical modeling to inform implementation of HIV prevention programs in the United States

Thesis (Ph.D.)--University of Washington, 2019Despite advances in the detection and treatment of HIV, the incidence of infection in the United States has increased in some subgroups over the past decade and remained stable in others. These trends point to a need for improved strategies for prevention that take into account the social, behavioral, and clinical context of different target populations. We conducted an internet-based survey to measure sexual behavior and use of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in Washington State (Chapter 1). Among 1,080 cisgender MSM respondents, 79% had heard of PrEP, 19% reported current use, and 36% of PrEP-naïve men reported that they wanted to start taking it. Among high-risk men recommended to initiate PrEP, 31% were taking it. With the data from this survey, in combination with secondary data from local surveillance systems and other surveys, we developed a dynamic network-based mathematical model to evaluate the potential impact of PrEP on HIV incidence in Washington MSM (Chapter 2). In the context of the high levels of testing and treatment in Washington, our model estimated that HIV incidence at the end of the 10-year simulation would be 48-83% lower with continued or increasing use of PrEP relative to a counterfactual scenario with no PrEP use. In chapter 3, we constructed a static linear mathematical model to estimate the impact and optimal age for one-time routine HIV screening in terms of case detection, person-years of undiagnosed infection, and progression to symptomatic HIV/AIDS. When added to prenatal, risk-based, symptom-based, and partner notification testing, our model estimated that the impact of routine screening is likely to be modest. The percent of tests resulting in new diagnoses exceeded the recommended minimum of 0.1% only in a setting with high HIV incidence in groups that don’t engage in repeat, targeted testing. The results from these three projects provide important insights to inform local policies and HIV prevention strategies, demonstrating the value of applying mathematical modeling to inform public health practice. Our findings highlight the influence of epidemiologic context on the impact of interventions such as PrEP and HIV screening, underscoring the importance of using local data to define context-specific prevention strategies

Impact of catch-up human papillomavirus vaccination on cervical cancer incidence in Kenya: A mathematical modeling evaluation of HPV vaccination strategies in the context of moderate HIV prevalence

BackgroundCervical cancer incidence is high in Kenya due to HIV and limited access to cancer prevention services. Human papillomavirus (HPV) has been shown to increase HIV acquisition; however, the potential impact of HPV vaccination on HIV is unknown. We modeled the health impact of HPV vaccination in the context of the HIV epidemiology in Kenya.MethodsUsing a validated compartmental transmission model of HIV and HPV set in Kenya, we evaluated five scenarios of nonavalent HPV vaccination: single-age-vaccination of 10-year-old girls at 90% coverage; multi-age-cohort (MAC) vaccination of 10-14-year-old girls at 90% coverage; MAC plus moderate-coverage (50%) catch-up vaccination of 15-24-year-old women; MAC plus high-coverage (80%) catch-up of 15-24-year-old women; and MAC plus catch-up of 15-44-year-old women at 80% coverage (HPV-FASTER). We compared cervical cancer incidence, HIV prevalence, and cumulative cervical cancer and HIV cases averted after 50 years to a baseline scenario without vaccination. In all scenarios, we assumed the UNAIDS 90-90-90 goal for HIV treatment is attained by 2030.FindingsIn 2021, model-estimated cervical cancer incidence is 44/100,000 and HIV prevalence among women is 6·5%. In 2070, projected cancer incidence declines to 27/100,000 and HIV prevalence reaches 0·3% without vaccination. With single-age-vaccination, cancer incidence in 2070 is reduced by 68%, averting 64,529 cumulative cancer cases. MAC vaccination reduces cancer incidence by 75%, averting 206,115 cancer cases. Moderate and high-coverage catch-up and HPV-FASTER reduce cancer incidence by 80%, 82%, and 84%, averting 254,930, 278,690, and 326,968 cancer cases, respectively. In all scenarios, HIV prevalence in 2070 is reduced by a relative 8-11%, with 15,609-34,981 HIV cases averted after 50 years.InterpretationHPV vaccination can substantially reduce cervical cancer incidence in Kenya in the next 50 years, particularly if women up to age 24 are vaccinated. HIV treatment scale-up can also alleviate cervical cancer burden. However, HPV vaccination has modest additional impact on HIV when antiretroviral therapy coverage is high.FundingNational Institutes of Health, Bill and Melinda Gates Foundation