Ruanne V Barnabas

The impact of HIV on cervical cancer elimination in KwaZulu-Natal: a comparative modeling analysis

Abstract Background Achieving cervical cancer (CC) elimination requires addressing disparities in CC burden for women living with HIV (WLHIV) and how disparities evolve in the context of antiretroviral therapy (ART) scale-up. To inform CC elimination for high HIV prevalence regions, we modeled the impact of HIV, HIV interventions, and CC interventions in KwaZulu-Natal, South Africa. Methods We used 2 independently developed, dynamic compartmental transmission models of HIV and human papillomavirus (DRIVE and Policy1-Cervix-HIV) calibrated to KwaZulu-Natal. We simulated: a counterfactual without HIV but with observed CC screening and vaccination; and scenarios sequentially adding condom use and voluntary medical male circumcision (VMMC); HIV; observed HIV and CC interventions (status quo); achieving United Nations Programme on HIV/AIDS HIV treatment targets; and achieving World Health Organization (WHO) CC elimination targets. The impact of each scenario was measured as the difference in CC incidence from the previous scenario. Results were reported from 2024 to 2124 as a range between the 2 models; CC elimination was WHO-defined as incidence <4/100 000 women-years. Results For the status quo, CC incidence ranged from 61.30 to 78.96/100 000 women-years in 2024, with the highest incidence among WLHIV (126.8-192.0/100 000). HIV contributed an estimated 29.08-48.87 additional cases per 100 000. Neither model predicted elimination under status quo interventions, but achieving HIV treatment and CC elimination targets could reduce incidence to 1.42-6.25/100 000 women-years in 2124. Conclusions HIV is associated with a population-level increase in CC incidence. However, scaling up ART coverage and CC interventions is expected to significantly reduce the burden of CC overall and among WLHIV. These conclusions are consistent between both models and strengthened by the comparative modeling approach.

State-level disparities in cervical cancer prevention and outcomes in the United States: a modeling study

Abstract Background Despite human papillomavirus (HPV) vaccines’ availability for over a decade, coverage across the United States varies. Although some states have tried to increase HPV vaccination coverage, most model-based analyses focus on national impacts. We evaluated hypothetical changes in HPV vaccination coverage at the national and state levels for California, New York, and Texas using a mathematical model. Methods We developed a new mathematical model of HPV transmission and cervical cancer, creating national- and state-level models, incorporating country- and state-specific vaccination coverage and cervical cancer incidence and mortality. We quantified the national- and state-level impact of increasing HPV vaccination coverage to 80% by 2025 or 2030 on cervical cancer outcomes and the time to elimination defined as less than 4 per 100 000 women. Results Increasing vaccination coverage to 80% in Texas over 10 years could reduce cervical cancer incidence by 50.9% (95% credible interval [CrI] = 46.6%-56.1%) by 2100, from 1.58 (CrI = 1.19-2.09) to 0.78 (CrI = 0.57-1.02) per 100 000 women. Similarly, New York could see a 27.3% (CrI = 23.9%-31.5%) reduction from 1.43 (CrI = 0.93-2.07) to 1.04 (CrI = 0.66-1.53) per 100 000 women, and California a 24.4% (CrI = 20.0%-30.0%) reduction from 1.01 (CrI = 0.66-1.44) to 0.76 (CrI = 0.50-1.09) per 100 000 women. Achieving 80% coverage in 5 years will provide slightly larger and sooner reductions. If the vaccination coverage levels in 2019 continue, cervical cancer elimination could occur nationally by 2051 (CrI = 2034-2064), but state timelines may vary by decades. Conclusion Targeting an HPV vaccination coverage of 80% by 2030 will disproportionately benefit states with low coverage and higher cervical cancer incidence. Geographically focused analyses can better inform priorities.

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.

Single-dose HPV vaccination efficacy among adolescent girls and young women in Kenya (the KEN SHE Study): study protocol for a randomized controlled trial

AbstractBackgroundHPV infection is the primary cause of cervical cancer, a leading cause of cancer among women in Kenya and many sub-Saharan African countries. High coverage of HPV vaccination is a World Health Organization priority to eliminate cervical cancer globally, but vaccine supply and logistics limit widespread implementation of the current two or three dose HPV vaccine schedule.MethodsWe are conducting an individual randomized controlled trial to evaluate whether a single dose of the bivalent (HPV 16/18) or nonavalent (HPV 16/18/31/33/45/52/58/6/11) HPV vaccine prevents persistent HPV infection, a surrogate marker for precancerous lesions and cervical cancer. The primary objective is to compare the efficacy of immediate, single-dose bivalent or nonavalent vaccination with delayed HPV vaccination. Kenyan women age 15–20 years old are randomized to immediate bivalent HPV and delayed meningococcal vaccine (group 1), immediate nonavalent HPV vaccine and delayed meningococcal vaccine (group 2), or immediate meningococcal vaccine and delayed HPV vaccine (group 3) with 36 months of follow-up. The primary outcome is persistent vaccine-type HPV infection by month 18 and by month 36 for the final durability outcome. The secondary objectives include to (1) evaluate non-inferiority of antibody titers among girls and adolescents (age 9 to 14 years) from another Tanzanian study, the DoRIS Study (NCT02834637), compared to KEN SHE Study participants; (2) assess the memory B cell immune response at months 36 and 37; and (3) estimate cost-effectiveness using the trial results and health economic models.DiscussionThis study will evaluate single-dose HPV vaccine efficacy in Africa and has the potential to guide public health policy and increase HPV vaccine coverage. The secondary aims will assess generalizability of the trial results by evaluating immunobridging from younger ages, durability of the immune response, and the long-term health benefits and cost of single-dose HPV vaccine delivery.Trial registrationClinicalTrials.govNCT03675256. Registered on September 18, 2018

Durability of single-dose HPV vaccination in young Kenyan women: randomized controlled trial 3-year results

AbstractCervical cancer burden is high where prophylactic vaccination and screening coverage are low. We demonstrated in a multicenter randomized, double-blind, controlled trial that single-dose human papillomavirus (HPV) vaccination had high vaccine efficacy (VE) against persistent infection at 18 months in Kenyan women. Here, we report findings of this trial through 3 years of follow-up. Overall, 2,275 healthy women aged 15–20 years were recruited and randomly assigned to receive bivalent (n = 760), nonavalent (n = 758) or control (n = 757) vaccine. The primary outcome was incident-persistent vaccine type-specific cervical HPV infection. The primary evaluation was superiority analysis in the modified intention-to-treat (mITT) HPV 16/18 and HPV 16/18/31/33/45/52/58 cohorts. The trial met its prespecified end points of vaccine type-specific persistent HPV infection. A total of 75 incident-persistent infections were detected in the HPV 16/18 mITT cohort: 2 in the bivalent group, 1 in the nonavalent group and 72 in the control group. Nonavalent VE was 98.8% (95% CI 91.3–99.8%, P < 0.0001) and bivalent VE was 97.5% (95% CI 90.0–99.4%, P < 0.0001). Overall, 89 persistent infections were detected in the HPV 16/18/31/33/45/52/58 mITT cohort: 5 in the nonavalent group and 84 in the control group; nonavalent VE was 95.5% (95% CI 89.0–98.2%, P < 0.0001). There were no vaccine-related severe adverse events. Three years after vaccination, single-dose HPV vaccination was highly efficacious, safe and conferred durable protection. ClinicalTrials.gov no. NCT03675256.