Enhanced cervical cancer and HIV interventions reduce the disproportionate burden of cervical cancer cases among women living with HIV: A modeling analysis.

INTRODUCTION: Women living with HIV experience heightened risk of cervical cancer, and over 50% of cases in Southern Africa are attributed to HIV co-infection. Cervical cancer interventions tailored by HIV status delivered with HIV antiretroviral therapy (ART) for treatment can decrease cancer incidence, but impact on HIV-related disparities remains understudied. METHODS: Using a dynamic model calibrated to KwaZulu-Natal, South Africa, we projected HIV prevalence, cervical cancer incidence, and proportion of cancer cases among women living with HIV between 2021-2071. Relative to the status quo of moderate intervention coverage, we modeled three additive scenarios: 1) ART scale-up only; 2) expanded human papillomavirus (HPV) vaccination, screening, and treatment; and 3) catch-up HPV vaccination and enhanced screening for women living with HIV. RESULTS: Under the status quo, HIV prevalence among women aged 15+ decreased from a median of 35% [Uncertainty Range (UR): 26-42%] in 2021 to 25% [19-34%] in 2071. The proportion of cervical cancer cases that were women living with HIV declined from 73% [63-86%] to 58% [47-74%], but incidence remained 4.3-fold [3.3-5.7] that of women without HIV. ART scale-up reduced HIV prevalence in 2071, but increased the incidence rate ratio to 5.2 [3.7-7.3]. Disparities remained after expanding cancer interventions for all women (incidence rate ratio: 4.8 [3.6-7.6]), while additional catch-up HPV vaccination and screening for women living with HIV decreased the incidence rate ratio to 2.7 [1.9-3.4] in 2071. CONCLUSIONS: Tailored cervical cancer interventions for women living with HIV can counteract rising cancer incidence incurred by extended life expectancy on ART and reduce disparate cancer burden.

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.

Modelling cervical cancer elimination using single-visit screening and treatment strategies in the context of high HIV prevalence: estimates for KwaZulu-Natal, South Africa.

INTRODUCTION: In settings with high HIV prevalence, cervical cancer incidence rates are up to six-fold higher than the global average of 13.1 cases per 100,000 women-years. To inform strategies for global cervical cancer elimination, we used a dynamic transmission model to evaluate scalable screening and treatment strategies, accounting for HIV-associated cancer risks and weighing prevention gains against overtreatment. METHODS: We developed a dynamic model of HIV-HPV co-infection and disease progression, which we calibrated to KwaZulu-Natal, South Africa. Our baseline scenario reflects the current practice of HPV vaccination with a multi-visit screening and treatment strategy involving cytology and colposcopy triage. We evaluated 13 comparator scenarios with increased vaccination coverage and one-time, two-time or repeat HIV-targeted cervical cancer screening with the following single-visit strategies: HPV DNA testing, HPV genotyping, automated visual evaluation (AVE) and HPV DNA with AVE triage. In all scenarios, HIV antiretroviral therapy, condom use and voluntary male medical circumcision continue at baseline levels. We simulated cancer incidence under each scenario from 2020 to 2120 using the 25 best-fitting parameter sets. We present the median and range of model output from these simulations to account for parameter uncertainty. RESULTS: We estimate that cervical cancer incidence will decrease by 87% with the continuation of current cervical cancer and HIV prevention strategies, from an age-standardized rate per 100,000 women of 80.4 (range 58.2, 112.1) in 2020 to 10.7 (4.2, 29.9) in 2120. Scenarios scaling up vaccination and single-visit strategies resulted in near- and long-term gains. With repeat HIV-targeted screening, incidence rates were projected to be 29-34% lower in 2030 relative to the baseline scenario, and elimination (incidence <4/100,000) was achieved with HPV DNA testing in 2095 and with AVE in 2114. A strategy of HPV DNA with AVE triage optimized the tradeoff between cancer cases averted and overtreatment. CONCLUSIONS: Single-visit screening strategies could avert a substantial burden of cervical cancer and accelerate progress towards elimination in settings with a high burden of HIV. Increasing the screening frequency among women with HIV and reducing loss-to-follow-up for treatment will be key components of a successful elimination strategy.

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.

BACKGROUND: Cervical 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. METHODS: Using 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. FINDINGS: In 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. INTERPRETATION: HPV 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. FUNDING: National Institutes of Health, Bill and Melinda Gates Foundation.

Differences in HIV Risk and Prevention Among Cisgender Latino Sexual Minority Men by Language of Online Survey Completion: Analysis of National and Washington State Data.

Internet-based surveys can be programmed and advertised in multiple languages to reach non-English-speaking individuals, but it is unclear the extent to which this enhances the diversity of participants and supports inclusion of individuals at higher risk for HIV. We sought to examine how language of survey completion (English or Spanish) was associated with sociodemographic characteristics and indicators of HIV risk and prevention among cisgender Latino sexual minority men (SMM). We analyzed national and Washington State data using the Understanding New Infections through Targeted Epidemiology (UNITE) Cohort Study (2017 and 2018) and the Washington HIV/STI Prevention Project (WHSPP) survey (2017 and 2018/2019), respectively. Latino SMM who completed online surveys in Spanish differed from those who completed surveys in English across several sociodemographic characteristics including age, education, and income. After adjusting for sociodemographic characteristics and HIV-related risk factors, Spanish language respondents in UNITE were less likely to have tested for HIV in the past year, and those in WHSPP were more likely to report a recent STI diagnosis. Findings suggest that Latino SMM who complete surveys in Spanish comprise a unique subgroup that may have a specific HIV health and risk behavior profile. Our results suggest a need for increased and tailored efforts to recruit and include Spanish-speaking Latino SMM for local and national research and public health programming.

RESUMEN: Encuestas por internet pueden ser programadas y anunciadas para alcanzar a personas que no hablan inglés, pero no queda claro si esto pueda mejorar la diversidad de los participantes de investigación y apoyar la inclusión de los individuos de alto riesgo a infección con el VIH. En este estudio examinamos la relación del idioma de completar la encuesta en línea (inglés o español) entre hombres Latinos de minorías sexuales (HLMS) cisgénero con características sociodemográficas y determinantes para el riesgo y prevención del VIH. Analizamos los datos nacionales y estatales con el estudio de cohorte de Understanding New Infections through Targeted Epidemiology (UNITE) (2017 y 2018) y El Proyecto de Washington para la Prevención del VIH/Infecciones de Transmisión Sexual (WHSPP) (2017 y 2018/2019), respectivamente. Los HLSM quienes completaron las encuestas por internet en español fueron diferentes a los que completaron las encuestas en inglés por varias características sociodemográficas incluso la edad, la educación, y el ingreso. Después de ajustar por las características sociodemográficas y los factores de riesgo asociados con el VIH, los participantes de UNITE que respondieron en español tuvieron menos probabilidad de haberse hecho la prueba de VIH en el año pasado y los que participaron en el WHSPP eran más probable que reportaran un diagnóstico de ITS. Los resultados indican que los HLSM quienes completan las encuestas en español representan un subgrupo distinto que tiene un perfil específico de comportamiento de riesgo y salud respecto al VIH. Los resultados demuestran la necesidad de mayores esfuerzos especializados para reclutar e incluir los HLSM quienes hablan español para que participen en las investigaciones en línea a nivel local y nacional y la programación de la salud pública.

Partnership dynamics in mathematical models and implications for representation of sexually transmitted infections: a review.

Mathematical models of sexually transmitted disease (STI) are increasingly relied on to inform policy, practice, and resource allocation. Because STI transmission requires sexual contact between two or more people, a model's ability to represent the dynamics of sexual partnerships can influence the validity of findings. This ability is to a large extent constrained by the model type, as different modeling frameworks vary in their capability to capture patterns of sexual contact at individual, partnership, and network levels. In this paper, we classify models into three groups: compartmental, individual-based, and statistical network models. For each framework, we describe the basic model structure and discuss key aspects of sexual partnership dynamics: how and with whom partnerships are formed, partnership duration and dissolution, and temporal overlap in partnerships (concurrency). We illustrate the potential implications of accurately accounting for partnership dynamics, but these effects depend on characteristics of both the population and pathogen; the combined impact of these partnership and epidemiologic dynamics can be difficult to predict. While each of the reviewed model frameworks may be appropriate to inform certain research or policy questions, modelers and consumers of models should carefully consider the implications of sexual partnership dynamics for the questions under study.

The Potential Impact of One-Time Routine HIV Screening on Prevention and Clinical Outcomes in the United States: A Model-Based Analysis.

BACKGROUND: US guidelines recommend routine human immunodeficiency virus (HIV) screening of all adults and adolescents at least once. The population-level impact of this strategy is unclear and will vary across the country. METHODS: We constructed a static linear model to estimate the optimal ages and incremental impact of adding 1-time routine HIV screening to risk-based, prenatal, symptom-based, and partner notification testing. Using surveillance data and published studies, we parameterized the model at the national level and for 2 settings representing subnational variability in the rates and distribution of infection: King County, WA and Philadelphia County, PA. Screening strategies were evaluated in terms of the percent of tests that result in new diagnoses (test positivity), cumulative person-years of undiagnosed infection, and the number of symptomatic HIV/acquired immune deficiency syndrome cases. RESULTS: Depending on the frequency of risk-based screening, routine screening test positivity was maximized at ages 30 to 34 years in the national model. The optimal age for routine screening was higher in a setting with a lower proportion of cases among men who have sex with men. Across settings, routine screening resulted in incremental reductions of 3% to 8% in years of undiagnosed infection and 3% to 11% in symptomatic cases, compared with reductions of 36% to 69% and 41% to 76% attributable to risk-based screening. CONCLUSIONS: Although routine HIV screening may contribute meaningfully to increased case detection in persons not captured by targeted testing programs in some settings, this strategy will have a limited impact on population-level outcomes. Our findings highlight the importance of a multipronged testing strategy with continued investment in risk-based screening programs.

Monitoring HIV Preexposure Prophylaxis Use Among Men Who Have Sex With Men in Washington State: Findings From an Internet-Based Survey.

BACKGROUND: Many state and local health departments now promote and support the use of HIV preexposure prophylaxis (PrEP), yet monitoring use of the intervention at the population level remains challenging. METHODS: We report the results of an online survey designed to measure PrEP use among men who have sex with men (MSM) in Washington State. Data on the proportion of men with indications for PrEP based on state guidelines and levels of awareness, interest, and use of PrEP are presented for 1080 cisgender male respondents who completed the survey between January 1 and February 28, 2017. We conducted bivariate and multivariable logistic regression to identify factors associated with current PrEP use. To examine patterns of discontinuation, we conducted Cox proportional hazards regression and fit a Kaplan-Meier curve to reported data on time on PrEP. RESULTS: Eighty percent of respondents had heard of PrEP, 19% reported current use, and 36% of men who had never used PrEP wanted to start taking it. Among MSM for whom state guidelines recommend PrEP, 31% were taking it. In multivariable analysis, current PrEP use was associated with older age, higher education, and meeting indications for PrEP use. Our data suggest that 20% of PrEP users discontinue within 12 months, and men with lower educational attainment were more likely to discontinue. CONCLUSIONS: Despite high levels of use, there is significant unmet need for PrEP in Washington. Our experience indicates that Internet surveys are feasible and informative for monitoring PrEP use in MSM.