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.

Association of Breast Cancer Screening Behaviors With Stage at Breast Cancer Diagnosis and Potential for Additive Multi-Cancer Detection via Liquid Biopsy Screening: A Claims-Based Study.

PURPOSE: To evaluate mammography uptake and subsequent breast cancer diagnoses, as well as the prospect of additive cancer detection via a liquid biopsy multi-cancer early detection (MCED) screening test during a routine preventive care exam (PCE). METHODS: Patients with incident breast cancer were identified from five years of longitudinal Blue Health Intelligence® (BHI®) claims data (2014-19) and their screening mammogram and PCE utilization were characterized. Ordinal logistic regression analyses were performed to identify the association of a biennial screening mammogram with stage at diagnosis. Additional screening opportunities for breast cancer during a PCE within two years before diagnosis were identified, and the method extrapolated to all cancers, including those without recommended screening modalities. RESULTS: Claims for biennial screening mammograms and the time from screening to diagnosis were found to be predictors of breast cancer stage at diagnosis. When compared to women who received a screening mammogram proximal to their breast cancer diagnosis (0-4 months), women who were adherent to guidelines but had a longer time window from their screening mammogram to diagnosis (4-24 months) had a 87% increased odds of a later-stage (stages III or IV) breast cancer diagnosis (p-value <0.001), while women with no biennial screening mammogram had a 155% increased odds of a later-stage breast cancer diagnosis (p-value <0.001). This highlights the importance of screening in the earlier detection of breast cancer. Of incident breast cancer cases, 23% had no evidence of a screening mammogram in the two years before diagnosis. However, 49% of these women had a PCE within that time. Thus, an additional 11% of breast cancer cases could have been screened if a MCED test had been available during a PCE. Additionally, MCED tests have the potential to target up to 58% of the top 5 cancers that are the leading causes of cancer death currently without a USPSTF recommended screening modality (prostate, pancreatic, liver, lymphoma, and ovarian cancer). CONCLUSION: The study used claims data to demonstrate the association of cancer screening with cancer stage at diagnosis and demonstrates the unmet potential for a MCED screening test which could be ordered during a PCE.