Robyn Margaret Stuart

Background: Nigeria introduced single-dose HPV vaccination for girls aged 9–14 in 2023, reaching approximately 60% aggregate coverage by 2025. While an important achievement, this remains short of the 90% coverage called for under the WHO’s 90-70-90 cervical cancer elimination targets, and further scale-up depends on reaching out-of-school girls. In this study we used a model of HPV transmission in Nigeria to quantify the residual cervical cancer burden under continued adolescent delivery, assess how additional screening scale-up and equity assumptions modify it, and identify the effective coverage requirements for an infant HPV vaccination program to be non-inferior to the existing adolescent strategy. Methods: We used HPVsim, an agent-based microsimulation calibrated to Nigerian sexual behavior, HPV prevalence, and cervical cancer incidence, to project new cervical cancer cases and age-standardized incidence over 2025–2100 under scenarios which vary vaccination delivery mode (status-quo adolescent, WHO 90-70-90 adolescent scale-up, and 60/75/90% infant delivery), screening coverage (opportunistic 15% vs. scaled 70% aggregate), and the degree to which primary school completion correlated with vaccination (odds ratio 1 vs. 5) and with screening (odds ratio 1 vs. 3). Infant delivery scenarios were run at hypothetical effective-vaccine-efficacy-at-exposure values of 50%, 70%, and 95% — scenario inputs bracketing the plausible waning range, not evidence-based estimates of infant vaccine performance (no HPV vaccine trial has enrolled anyone below age 10). Each scenario was run at 50 replicates (10 calibration draws × 5 seeds); reported outcomes are the median across replicates and uncertainty ranges are interquartile (25th–75th percentile). Results: Continuation of Nigeria’s current adolescent program is projected to avert 1.82 million cervical cancer cases (IQR 1.65–1.90 million; 95% UI 1.39–2.02 million) over 2025–2100 (a 53% reduction relative to no vaccination, IQR 51–55%; 95% UI 46–58%), with age-standardized incidence falling from 19.7 to 7.8 per 100,000 by 2100. However, 82% of the near-term (2025–2075) burden is projected to fall on the pre-2015 birth cohort, i.e. women already beyond the vaccination target age, leaving approximately 945,000 residual cases (IQR 905K–1.00M; 95% UI 835K–1.14M) in this cohort. Scaling up screening to WHO targets was estimated to avert a further ∼387K cases (IQR 331–424K; 95% UI 269–515K), roughly 25% of the residual burden; results were about 6–8% better if the scale-up instead reached all women equitably regardless of education. Under a hypothetical scenario of infant vaccination at 90% coverage and 95% effective vaccine efficacy at exposure (matching adolescent-age performance), outcomes were comparable to full WHO adolescent scale-up (49% vs. 54% reduction in vaccine-targetable cohort cancers), but under a hypothetical 50% effective efficacy at Nigeria’s DTP3-anchored 62% coverage the strategy averted only a fraction of these cancers. Conclusions: The near-term cervical cancer burden in Nigeria is dominated by cohorts vaccination cannot reach; scaling screening for them is the more consequential lever over the coming three decades and rests on established evidence. Findings on infant HPV delivery are exploratory and hypothesis-generating: they depend on three unverified empirical prerequisites – infant HPV vaccine immunogenicity in the first months of life, durability of protection across the ∼15–25-year interval to peak HPV exposure, and coverage achievable through Nigeria’s routine childhood immunization platform – and should not be read as a basis for any policy recommendation contingent on infant HPV delivery until those prerequisites are established.

Background: Zimbabwe’s national guidelines for sexually transmitted infection (STI) management recommend that high-risk women presenting with vaginal discharge syndrome (VDS) are prescribed antibiotics for gonorrhoea ( Neisseria gonorrhoeae (NG)), chlamydia ( Chlamydia trachomatis (CT)), trichomoniasis ( Trichomonas vaginalis (TV)) and bacterial vaginosis (BV). The performance of this approach depends on its clinical interpretation and implementation. Here, we investigate the potential relative impact of an NG/CT/TV point-of-care (POC) test on undertreatment, overtreatment and disease burden in the context of different implementations of syndromic management of women with VDS. Methods: We created an agent-based model with an age- and risk-stratified sexual network and modelled co-circulation of NG, CT and TV along with HIV and BV. We estimated symptomatic proportions and care-seeking rates under three different scenarios around the implementation of treatment guidelines, corresponding to all, most or half of women being treated for NG+CT upon presentation with VDS. For each implementation scenario, we estimated disease burden and over/undertreatment rates assuming continuation of the standard of care with/without a POC NG/CT/TV test available over 2027–2040. Results: Under a treat-all interpretation of the syndromic management guidelines, we estimate that 70%–80% of antibiotics for NG/CT would currently be given to women without these infections. Overtreatment would fall to less than 5% if a sensitive POC test for NG/CT/TV were available. However, if the implementation of the guidelines implies that only half of women seeking care for VDS are treated, then a POC test would also reduce undertreatment and disease burden, with >500 000 additional women correctly treated for NG and ~1.5 million correctly treated for CT and TV, and 24%/15% reductions in the number of women with NG/CT by 2040. Conclusion: Improved data on the functioning of syndromic management in practice would help refine the estimates of the health impact and the overall value proposition of a highly sensitive POC diagnostic for NG/CT/TV. However, even without such data, our analysis demonstrates the potential for such a diagnostic to reduce overtreatment by >90% relative to plausible assumptions regarding the standard of care.

Syndromic management remains the standard approach for sexually transmitted infection (STI) care in many low-resource settings. Recent advances in point-of-care (POC) diagnostic testing offer the opportunity to improve STI case management by enabling targeted treatment, reducing unnecessary antibiotic use, and strengthening partner services. This educational article summarizes key insights from a symposium organised by the World Health Organization and Gates Foundation at the STI & HIV World Congress 2025. Evidence from modeling studies in Zimbabwe and South Africa demonstrates significant reductions in overtreatment and population-level STI burden with POC test integration. Acceptability among end-users and providers is high, contingent on rapid, confidential testing linked to same-day treatment. The article reviews the current landscape of STI POC tests, including WHO’s REASSURED criteria and target product profiles, and discusses regulatory progress and technical specifications for prequalification. Implementation strategies emphasize integration into existing health services, capacity building, stakeholder engagement and importance of robust quality assurance processes. While cost-effectiveness data remain limited, strategic investment and policy development are essential to scale up STI POC testing. With growing technological feasibility and public health urgency, POC testing represents a paradigm shift in STI management, offering a pathway to more effective, equitable, and sustainable care in resource-constrained settings.

Background: Characterising disparities in HIV infection across populations by gender, age, and HIV risk is key information to guide intervention priorities. We compared 9 models representing 15 different settings across Africa to assess how indicators measuring HIV acquisitions, transmissions, or potential long-term infections influence estimates of the contribution of different populations to new infections, including key populations (KPs, including female sex workers (FSW), their clients, men who have sex with men). Methods: We evaluated four indicators: I ₁ ) acquisition indicator measuring the annual fraction of all new infections acquired by a specific population, I ₂ ) direct transmission indicator measuring the annual fraction of all new infections directly transmitted by a specific population, I ₃ ) 1-year and I ₄ ) 10-year transmission population-attributable fractions ( tPAFs ). tPAFs measure the fraction of new infections averted if transmission involving a specific population was blocked over a specific time period. We compared estimates of the four indicators across 7 populations and 15 settings and assessed if the contribution of specific populations is ranked differently across indicators for 10 settings. Findings: Indicators identified distinct priority populations as the largest contributors: The acquisition indicator (I ₁ ) identified women aged 25+ years outside KPs as contributing the most to acquired infections in 8/10 settings in 2020, but to direct transmissions (I ₂ ) in only two settings. In 6/10 settings, the 10-year tPAFs (I ₄ ) identified non-KP men aged 25+ years and clients of FSW as the largest contributors to HIV transmission. Notably, non-KP women aged 15-24 years acquired (I ₁ ) more infections in 2020 (median of 1·7-fold across models) than they directly transmitted (I ₂ ), while non-KP men aged 25+ years and clients of FSWs transmitted more infections than they acquired in all but one model (median: 1·4 and 1·6-fold, respectively). Estimates of the 10-year tPAFs accounting for transmission in the long-term were substantially larger than the direct transmission indicator for all populations, especially for FSW (median: 2·0-fold). Interpretation: Indicators that reflect HIV acquisitions and transmissions over the short and long term can be utilised to capture the complexity of HIV epidemics across different populations and timeframes. The added nuance would improve the effectiveness of the HIV prevention response across all populations at risk. Funding: NIH, MRC. Research in context: Evidence before this study: Measures of the distribution of HIV acquisition across population groups are commonly used for assessing the contribution of populations to new HIV infections and prevention priorities. However, alternative indicators documented in the literature reflect transmissions or potential long-term effects. It is unclear how the choice of indicator affects the identification of populations that require additional prevention and treatment efforts to accelerate progress towards ending AIDS. We searched PubMed on March 08, 2025, with the terms (HIV) AND (Africa*) AND (acqui*) AND (transm*) AND (model*), with no language or publication date restriction, and identified no meta-assessment or mathematical model comparison studying differences in estimates of the fraction of all infections acquired and transmitted by a population when using different epidemiological indicators. Added value of this study: Using estimates from 9 models representing 15 different epidemic settings across Africa, we studied indicators of HIV epidemic contribution for 7 populations, including female sex workers, their clients, men who have sex with men, and non-key populations stratified by gender and age. We measured four commonly reported indicators of HIV contribution. One focused on acquired infections and the other three focused on transmissions. We found that estimates from these different indicators can differ greatly for the same model and population, to the extent that they identify different populations for prioritising interventions to accelerate HIV incidence declines. The acquisition-focused indicator (i.e. fraction of all infections acquired by a given population), the most used and communicated by UNAIDS, substantially underestimates the large contribution of men, and particularly male clients of female sex workers, to ongoing HIV transmission. Implications of all the available evidence: The choice of indicators measuring a population’s contribution to the HIV epidemic should be carefully considered and precisely defined. Modelling teams working in partnership with government, implementers, funders, and community members should systematically report both acquisition- and (long-term) transmission-focused indicators, instead of only measuring acquisitions in the short term as currently done. Multiple indicators will more comprehensively capture the potential impact of prevention efforts addressing acquisition and transmission risks of different vulnerable populations.

In 2020, the WHO launched its first global strategy to accelerate the elimination of cervical cancer, outlining an ambitious set of targets for countries to achieve over the next decade. At the same time, new tools, technologies, and strategies are in the pipeline that may improve screening performance, expand the reach of prophylactic vaccines, and prevent the acquisition, persistence and progression of oncogenic HPV. Detailed mechanistic modelling can help identify the combinations of current and future strategies to combat cervical cancer. Open-source modelling tools are needed to shift the capacity for such evaluations in-country. Here, we introduce the Human papillomavirus simulator (HPVsim), a new open-source software package for creating flexible agent-based models parameterised with country-specific vital dynamics, structured sexual networks, and co-transmitting HPV genotypes. HPVsim includes a novel methodology for modelling cervical disease progression, designed to be readily adaptable to new forms of screening. The software itself is implemented in Python, has built-in tools for simulating commonly-used interventions, includes a comprehensive set of tests and documentation, and runs quickly (seconds to minutes) on a laptop. Performance is greatly enhanced by HPVsim’s multiscale modelling functionality. HPVsim is open source under the MIT License and available via both the Python Package Index (via pip install) and GitHub (hpvsim.org).

Human papillomavirus (HPV) is the cause of almost all cases of cervical cancer, a disease that kills some 340,000 women per year. The timeline from initial infection with HPV to the onset of invasive cervical cancer spans decades, and observational studies of this process are limited to settings in which treatment of precancerous lesions was withheld or inadequate. Such studies have been critical for understanding the natural history of HPV, but some uncertainty remains as to how generalizable this process is across geographical settings, especially given variation in the prevalence of factors known to affect the host-side immune response to HPV, such as HIV and tobacco use. In this study, we create models for the 30 most populous countries in Sub-Saharan Africa, each with country-specific demographic, and behavioral inputs. We found that it was not possible to fit the data if we assumed that the natural history parameters were the same for all countries, even after accounting for demographic and behavioral differences, but that we could achieve a good fit with the addition of a single immunocompetence parameter for each country. Our results indicate that variation in host immune responses may play a role in explaining the differences in the burden of cervical cancer between countries, which in turn implies a greater need for more geographically diverse data collection to understand the natural history of HPV.

In 2020, the WHO launched its first Global Strategy to Accelerate the Elimination of Cervical Cancer, outlining an ambitious set of targets for countries to achieve over the next decade. At the same time, new tools, technologies, and strategies are in the pipeline that may improve screening performance, expand the reach of prophylactic vaccines, and prevent the acquisition, persistence and progression of oncogenic HPV. Detailed mechanistic modeling can help identify the combinations of current and future strategies to combat cervical cancer. Open-source modeling tools are needed to shift the capacity for such evaluations in-country. Here, we introduce the Human papillomavirus simulator (HPVsim), a new, flexible agent-based model that can be parameterized with country-specific vital dynamics, structured sexual networks, co-transmitting HPV genotypes, B- and T-cell mediated immunity, and high-resolution disease natural history. HPVsim is designed with a user-first lens: it is implemented in Python, has built-in tools for simulating commonly-used interventions, includes a comprehensive set of tests and documentation, and runs quickly (seconds to minutes) on a laptop. Useful complexity was not sacrificed: the platform is flexible, allowing bespoke scenario modeling. Author summary Mathematical models have been integral in setting ambitious goals for cervical cancer elimination, along with determining intermediate targets for vaccination, screening, and treatment. However, given that elimination strategies encompass decade-long timelines, these targets will inevitably need updating over time as the landscape of available technologies for combating cervical cancer evolves. In this work, we introduce a new model, HPVsim, which can rapidly evaluate pathways toward elimination under complex combinations of new and existing interventions. HPVsim is a flexible agent-based model with country-specific vital dynamics, structured sexual networks, co-transmitting HPV genotypes, B- and T-cell mediated immunity, and high-resolution disease natural history. Written in Python, with easy installation and full testing and documentation, the model is designed so that analysis pipelines can be created with very little effort. By improving access to cervical cancer modeling tools, we aim to enable real-time updates and nimble adaptation of cervical cancer elimination targets in response to changing technologies providing realistic targets on the path to cervical cancer elimination.

Despite the push towards evidence-based health policy, decisions about how to allocate health resources are all too often made on the basis of political forces or a continuation of the status quo. This results in wastage in health systems and loss of potential population health. However, if health systems are to serve people best, then they must operate efficiently and equitably, and appropriate valuation methods are needed to determine how to do this. With the advances in computing power over the past few decades, advanced mathematical optimization algorithms can now be run on personal computers and can be used to provide comprehensive, evidence-based recommendations for policymakers on how to prioritize health spending considering policy objectives, interactions of interventions, real-world system constraints and budget envelopes. Such methods provide an invaluable complement to traditional or extended cost-effectiveness analyses or league tables. In this paper, we describe how such methods work, how policymakers and programme managers can access them and implement their recommendations and how they have changed health spending in the world to date.