Michaela Hall

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.

Could HPV Testing on Self-collected Samples Be Routinely Used in an Organized Cervical Screening Program? A Modeled Analysis

Abstract Background: Cervical screening on self-collected samples has mainly been considered for targeted use in underscreened women. Updated evidence supports equivalent sensitivity of PCR-based human papillomavirus (HPV) testing on self-collected and clinician-collected samples. Methods: Using a well-established model, we compared the lifetime impact on cancer diagnoses and deaths resulting from cervical screening using self-collected samples only, with and without the existing restriction in Australia to women aged 30+ years and ≥2 years overdue, compared with the mainstream program of 5-yearly HPV screening on clinician-collected samples starting at 25 years of age. We conservatively assumed sensitivity of HPV testing on self-collected relative to clinician-collected samples was 0.98. Outcomes were estimated either in the context of HPV vaccination (“routinely vaccinated cohorts;” uptake as in Australia) or in the absence of HPV vaccination (“unvaccinated cohorts”). Results: In unvaccinated cohorts, the health benefits of increased participation from self-collection outweighed the worst case (2%) loss of relative test sensitivity even if only 15% of women, who would not otherwise attend, used it (“additional uptake”). In routinely vaccinated cohorts, population-wide self-collection could be marginally (0.2%–1.0%) less effective at 15% additional uptake but 6.2% to 12.4% more effective at 50% additional uptake. Most (56.6%–65.0%) of the loss in effectiveness in the restricted self-collection pathway in Australia results from the requirement to be 2 or more years overdue. Conclusions: Even under pessimistic assumptions, any potential loss in test sensitivity from self-collection is likely outweighed by improved program effectiveness resulting from feasible levels of increased uptake. Impact: Consideration could be given to offering self-collection more widely, potentially as an equal choice for women. See related commentary by Lim, p. 245

The past, present and future impact of HIV prevention and control on HPV and cervical disease in Tanzania: A modelling study

Women with HIV have an elevated risk of HPV infection, and eventually, cervical cancer. Tanzania has a high burden of both HIV and cervical cancer, with an HIV prevalence of 5.5% in women in 2018, and a cervical cancer incidence rate among the highest globally, at 59.1 per 100,000 per year, and an estimated 9,772 cervical cancers diagnosed in 2018. We aimed to quantify the impact that interventions intended to control HIV have had and will have on cervical cancer in Tanzania over a period from 1995 to 2070. A deterministic transmission-dynamic compartment model of HIV and HPV infection and natural history was used to simulate the impact of voluntary medical male circumcision (VMMC), anti-retroviral therapy (ART), and targeted pre-exposure prophylaxis (PrEP) on cervical cancer incidence and mortality from 1995-2070. We estimate that VMMC has prevented 2,843 cervical cancer cases and 1,039 cervical cancer deaths from 1995-2020; by 2070 we predict that VMMC will have lowered cervical cancer incidence and mortality rates by 28% (55.11 cases per 100,000 women in 2070 without VMMC, compared to 39.93 with VMMC only) and 26% (37.31 deaths per 100,000 women in 2070 without VMMC compared to 27.72 with VMMC), respectively. We predict that ART will temporarily increase cervical cancer diagnoses and deaths, due to the removal of HIV death as a competing risk, but will ultimately further lower cervical cancer incidence and mortality rates by 7% (to 37.31 cases per 100,000 women in 2070) and 5% (to 26.44 deaths per 100,000 women in 2070), respectively, relative to a scenario with VMMC but no ART. A combination of ART and targeted PrEP use is anticipated to lower cervical cancer incidence and mortality rates to 35.82 and 25.35 cases and deaths, respectively, per 100,000 women in 2070. HIV treatment and control measures in Tanzania will result in long-term reductions in cervical cancer incidence and mortality. Although, in the near term, the life-extending capability of ART will result in a temporary increase in cervical cancer rates, continued efforts towards HIV prevention will reduce cervical cancer incidence and mortality over the longer term. These findings are critical background to understanding the longer-term impact of achieving cervical cancer elimination targets in Tanzania.

Elimination of cervical cancer in Tanzania: Modelled analysis of elimination in the context of endemic HIV infection and active HIV control

AbstractThe World Health Organisation (WHO) has launched a strategic initiative for cervical cancer (CC) elimination which involves scaling up three interventions: human papillomavirus (HPV) vaccination, twice‐lifetime HPV‐screening screening and pre‐cancer/cancer treatment by 2030. CC is challenging to control in countries with endemic human immunodeficiency virus (HIV), as women living with HIV (WLHIV) are at elevated risk of HPV infection, persistence and progression. This analysis estimated the impact of the elimination interventions on CC incidence and mortality but additionally considered more intensive screening for WLHIV, using Tanzania as an example. A dynamic HIV/HPV model was used to simulate the elimination strategy for vaccination, screening and pre‐cancer/cancer treatment, with 3‐yearly HPV‐screening in WLHIV starting at age 25 years, in the context of sustained HIV control in Tanzania from 2020 to 2119. Without vaccination or HPV screening, CC incidence rates per 100 000 women are predicted to fall from 58.0 in 2020 to 41.6 (range: 39.1‐44.7) in 2119, due to existing HIV control. HPV vaccination and twice‐lifetime HPV‐screening for the general population and 3‐yearly screening for WLHIV, would reduce CC incidence to 1.3 (range: 1.3‐2.5) by 2119, with elimination (<4/100 000) in 2076 (range: 2076‐2092). CC mortality rates per 100 000 women are predicted to reach 1.1 (range: 1.1‐2.1) with further reductions contingent on increased CC treatment access. Vaccination and 3‐yearly HPV‐screening for WLHIV is predicted to achieve elimination in the subgroup of WLHIV potentially as early as 2061 (range: 2061‐2078), with a 2119 CC incidence rate of 1.7 (range: 1.7‐3.3). Scaling‐up vaccination and HPV‐screening will substantially reduce CC incidence in Tanzania, with elimination predicted within a century. Three‐yearly HPV‐screening and HPV vaccination, at high coverage rates, would facilitate CC elimination among WLHIV, and thus accelerate elimination in the overall population.

Benefits and harms of cervical screening, triage and treatment strategies in women living with HIV

Abstract To support a strategy to eliminate cervical cancer as a public health problem, the World Health Organisation (WHO) reviewed its guidelines for screening and treatment of cervical pre-cancerous lesions in 2021. Women living with HIV have 6-times the risk of cervical cancer compared to women in the general population, and we harnessed a model platform (‘Policy1-Cervix-HIV’) to evaluate the benefits and harms of a range of screening strategies for women living with HIV in Tanzania, a country with endemic HIV. Assuming 70% coverage, we found that 3-yearly primary HPV screening without triage would reduce age-standardised cervical cancer mortality rates by 72%, with a number needed to treat (NNT) of 38.7, to prevent a cervical cancer death. Triaging HPV positive women before treatment resulted in minimal loss of effectiveness and had more favorable NNTs (19.7–33.0). Screening using visual inspection with acetic acid (VIA) or cytology was less effective than primary HPV and, in the case of VIA, generated a far higher NNT of 107.5. These findings support the WHO 2021 recommendation that women living with HIV are screened with primary HPV testing in a screen-triage-and-treat approach starting at 25 years, with regular screening every 3–5 years.

Benefits, harms and cost-effectiveness of cervical screening, triage and treatment strategies for women in the general population

Abstract In 2020, the World Health Organization (WHO) launched a strategy to eliminate cervical cancer as a public health problem. To support the strategy, the WHO published updated cervical screening guidelines in 2021. To inform this update, we used an established modeling platform, Policy1-Cervix , to evaluate the impact of seven primary screening scenarios across 78 low- and lower-middle-income countries (LMICs) for the general population of women. Assuming 70% coverage, we found that primary human papillomavirus (HPV) screening approaches were the most effective and cost-effective, reducing cervical cancer age-standardized mortality rates by 63–67% when offered every 5 years. Strategies involving triaging women before treatment (with 16/18 genotyping, cytology, visual inspection with acetic acid (VIA) or colposcopy) had close-to-similar effectiveness to HPV screening without triage and fewer pre-cancer treatments. Screening with VIA or cytology every 3 years was less effective and less cost-effective than HPV screening every 5 years. Furthermore, VIA generated more than double the number of pre-cancer treatments compared to HPV. In conclusion, primary HPV screening is the most effective, cost-effective and efficient cervical screening option in LMICs. These findings have directly informed WHO’s updated cervical screening guidelines for the general population of women, which recommend primary HPV screening in a screen-and-treat or screen-triage-and-treat approach, starting from age 30 years with screening every 5 years or 10 years.

Elimination of cervical cancer: the impact of HPV vaccination, primary HPV screening, and expanded access to cancer treatment services

In 2022, over 662,000 cases of cervical cancer were diagnosed globally and over 348,000 deaths occurred from the disease, with almost 94 % of these deaths occurring in low- and lower-middle income countries (LMIC). Effective intervention strategies, including prophylactic Human Papillomavirus (HPV) vaccination for adolescents and primary HPV screening for adult women, are highly effective and cost-effective methods of prevention; however, delivering population-wide access to these prevention methods has been challenging, particularly in LMIC. The World Health Organization (WHO) has launched a global strategy for the elimination of cervical cancer as a public health problem through the scale-up of HPV vaccination, cervical screening and precancer and cancer treatment services. In this review article, we present the rationale, history and strategy behind the global cervical cancer elimination efforts, including the evidence underpinning the WHO's three pillars of cervical cancer control, and essential considerations for implementation, sustainable financing, and health systems implications. Many countries and regions are currently formulating frameworks to achieve cervical cancer elimination within their setting. Here, we consider implementation challenges for both LMIC, and high-income countries (HIC), calling upon the experiences of implementation guided by the WHO Western Pacific Region and Australian frameworks as exemplar settings.