Sinead Delany-Moretlwe

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.

Diagnostic accuracy of cervical cancer screening and screening–triage strategies among women living with HIV-1 in Burkina Faso and South Africa: A cohort study

Background Cervical cancer screening strategies using visual inspection or cytology may have suboptimal diagnostic accuracy for detection of precancer in women living with HIV (WLHIV). The optimal screen and screen–triage strategy, age to initiate, and frequency of screening for WLHIV remain unclear. This study evaluated the sensitivity, specificity, and positive predictive value of different cervical cancer strategies in WLHIV in Africa. Methods and findings WLHIV aged 25–50 years attending HIV treatment centres in Burkina Faso (BF) and South Africa (SA) from 5 December 2011 to 30 October 2012 were enrolled in a prospective evaluation study of visual inspection using acetic acid (VIA) or visual inspection using Lugol’s iodine (VILI), high-risk human papillomavirus DNA test (Hybrid Capture 2 [HC2] or careHPV), and cytology for histology-verified high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) at baseline and endline, a median 16 months later. Among 1,238 women (BF: 615; SA: 623), median age was 36 and 34 years (p < 0.001), 28.6% and 49.6% ever had prior cervical cancer screening (p < 0.001), and 69.9% and 64.2% were taking ART at enrolment (p = 0.045) in BF and SA, respectively. CIN2+ prevalence was 5.8% and 22.4% in BF and SA (p < 0.001), respectively. VIA had low sensitivity for CIN2+ (44.7%, 95% confidence interval [CI] 36.9%–52.7%) and CIN3+ (56.1%, 95% CI 43.3%–68.3%) in both countries, with specificity for ≤CIN1 of 78.7% (95% CI 76.0%–81.3%). HC2 had sensitivity of 88.8% (95% CI 82.9%–93.2%) for CIN2+ and 86.4% (95% CI 75.7%–93.6%) for CIN3+. Specificity for ≤CIN1 was 55.4% (95% CI 52.2%–58.6%), and screen positivity was 51.3%. Specificity was higher with a restricted genotype (HPV16/18/31/33/35/45/52/58) approach (73.5%, 95% CI 70.6%–76.2%), with lower screen positivity (33.7%), although there was lower sensitivity for CIN3+ (77.3%, 95% CI 65.3%–86.7%). In BF, HC2 was more sensitive for CIN2+/CIN3+ compared to VIA/VILI (relative sensitivity for CIN2+ = 1.72, 95% CI 1.28–2.32; CIN3+: 1.18, 95% CI 0.94–1.49). Triage of HC2-positive women with VIA/VILI reduced the number of colposcopy referrals, but with loss in sensitivity for CIN2+ (58.1%) but not for CIN3+ (84.6%). In SA, cytology high-grade squamous intraepithelial lesion or greater (HSIL+) had best combination of sensitivity (CIN2+: 70.1%, 95% CI 61.3%–77.9%; CIN3+: 80.8%, 95% CI 67.5%–90.4%) and specificity (81.6%, 95% CI 77.6%–85.1%). HC2 had similar sensitivity for CIN3+ (83.0%, 95% CI 70.2%–91.9%) but lower specificity compared to HSIL+ (42.7%, 95% CI 38.4%–47.1%; relative specificity = 0.57, 95% CI 0.52–0.63), resulting in almost twice as many referrals. Compared to HC2, triage of HC2-positive women with HSIL+ resulted in a 40% reduction in colposcopy referrals but was associated with some loss in sensitivity. CIN2+ incidence over a median 16 months was highest among VIA baseline screen-negative women (2.2%, 95% CI 1.3%–3.7%) and women who were baseline double-negative with HC2 and VIA (2.1%, 95% CI 1.3%–3.5%) and lowest among HC2 baseline screen-negative women (0.5%, 95% CI 0.1%–1.8%). Limitations of our study are that WLHIV included in the study may not reflect a contemporary cohort of WLHIV initiating ART in the universal ART era and that we did not evaluate HPV tests available in study settings today. Conclusions In this cohort study among WLHIV in Africa, a human papillomavirus (HPV) test targeting 14 high-risk (HR) types had higher sensitivity to detect CIN2+ compared to visual inspection but had low specificity, although a restricted genotype approach targeting 8 HR types decreased the number of unnecessary colposcopy referrals. Cytology HSIL+ had optimal performance for CIN2+/CIN3+ detection in SA. Triage of HPV-positive women with HSIL+ maintained high specificity but with some loss in sensitivity compared to HC2 alone.