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CL Hathaway et al. (August 2023). Understanding HPV prevention and control in women living with HIV. www.HPVWorld.com, 240

Introduction
In November 2020, the World Health Organization (WHO) launched its cervical cancer elimination strategy, aiming to reduce incidence to less than 4 per 100,000 women through three interventions: 1) vaccinating 90% of girls by age 15 years, 2) screening 70% of women twice in their lifetime, and 3) treating 90% of women with precancers or invasive cervical cancer.¹ Key to elimination are interventions that are tailored to women with HIV, a population at higher risk of HPV acquisition and persistence and invasive cervical cancer.² Modeling studies that explicitly include HPV and HIV synergies can evaluate the long-term impact of interventions on women with HIV, particularly HPV vaccination, cervical screening, and pre-cancer treatment.

The Impact of HPV Vaccination
HIV exacerbates the risk of cervical cancer; up to 53% of cervical cancers can be attributed to HIV.³ Models of Tanzania and Kenya have shown that even without additional interventions, we expect a 28% decline in cervical cancer incidence in the overall population by achieving high antiretroviral therapy (ART) coverage.^4,5 Increasing ART coverage will reduce new HIV infections and the risk of progressing to invasive cervical cancer in women with HIV. However, HIV interventions alone are not sufficient to reach the elimination threshold. Incorporating HPV vaccination in addition to ART scale-up will lead to more significant and rapid cervical cancer declines (Figure 1).^4,5

While the WHO recommends vaccinating girls aged 9-15 years, some countries such as Kenya are vaccinating only 10-year-old girls due to limited vaccine supplies and funding. While this approach can lead to large cervical cancer reductions, in the Tanzania model, time to elimination is still almost 100 years even when assuming high vaccination coverage (90%).⁵ However, in the Kenya model, greater and earlier incidence reduction is projected if short-term catch-up vaccination of young adult women is implemented.⁴ The Kenya model projects that over 50 years, 114,000 cumulative cancer cases can be averted if catch-up vaccination is available for women up to age 24 compared with single-age vaccination. However, even when catch-up vaccination is expanded to women up to age 44, elimination would still not be achieved in the next 50 years. This suggests that expanded vaccination coverage is not sufficient, highlighting the added importance of expanding screening strategies as part of a comprehensive cervical cancer elimination program.

The Impact of Cervical Screening
Vaccination is the most impactful parameter for cervical cancer reduction, but screening and increased access to treatment can also reduce cases and deaths (Figure 2). Vaccination benefits are seen in the longer term, but screening has more immediate effects by preventing cervical cancer and detecting it at an earlier stage when survival is greater. This is illustrated in the Tanzania model, which predicts that HPV vaccination will eliminate cervical cancer in 2106, but with the addition of screening for women with HIV, elimination can occur 30 years earlier.⁵

Various cervical screening methods are available based on resources and expertise. Screening methods include cytology, Visual Inspection with Acetic Acid (VIA), or HPV-DNA. However, it is important to note that WHO have unequivocally recommended primary HPV screening with triage for women living with HIV. Triage often follows HPV-DNA testing and includes genotyping, colposcopy, VIA, or cytology. Treatment services include thermal ablation cryotherapy or large loop excision of the transformation zone (LLETZ). Modeling analyses have assessed the impact of different screening strategies. A South Africa model estimates that replacing cytology-based screening with HPV testing can result in a 32% decrease in cervical cancer incidence in the short term because of superior test performance.⁶ Additionally, a significant challenge to cervical screening is loss-to-follow-up (LTFU), so any strategy that prioritizes screening, triage, and treatment in the same clinic or the same visit will lead to greater cervical cancer reduction. A different model for Kenya noted similar reduction in scenarios using VIA and HPV testing, likely because while VIA has lower sensitivity it benefits from lower LTFU and same-day screen-and-treat.⁶ Ultimately, same-day HPV-DNA testing can avert the greatest number of cervical cancer cases by maximizing sensitivity and minimizing LTFU.⁷

Conclusion
In countries with high HIV burden, cervical cancer prevention policies tailored to women with HIV must also be a component of the elimination strategy. Modeling studies have shown that high-coverage vaccination of young girls will have the greatest impact, but cervical screening will also be necessary for more immediate reductions in cervical cancer incidence and mortality, as well as long-term elimination.

DISCLOSURE
RB has received grants from KEN-SHE (Grant OPP1188693) and NCI CISNET (Grant U01 CA199334), and has received support from Regeneron Pharmaceuticals for article writing outside of this work. GL is a current employee of Merck & Co., Inc. CH has no conflicts of interest to disclose.



References

1. WHO. Global strategy to accelerate the elimination of cervical cancer as a public health problem. Geneva: World Health Organization; 2020. Available from: https://www.who.int/publications/i/item/9789240014107

2. Liu G, Sharma M, Tan N, Barnabas RV. HIV-positive women have higher risk of human papillomavirus infection, precancerous lesions, and cervical cancer. AIDS (London, England). 2018;32(6):795-808. Available from: https://doi.org/10.1097/qad.0000000000001765

3. Stelzle D, Tanaka LF, Lee KK, et al. Estimates of the global burden of cervical cancer associated with HIV. Lancet Glob Health. 2021 Feb;9(2):e161-e169. Available from: https://doi.org/10.1016/s2214-109x(20)30459-9

4. Liu G, Mugo NR, Bayer C, et al. Impact of catch-up human papillomavirus vaccination on cervical cancer incidence in Kenya: A mathematical modeling evaluation of HPV vaccination strategies in the context of moderate HIV prevalence. EClinicalMedicine. 2022;45: 101306. Available from: https://doi.org/10.1016/j.eclinm.2022.101306

5. Hall MT, Smith MA, Simms KT, et al. Elimination of cervical cancer in Tanzania: Modelled analysis of elimination in the context of endemic HIV infection and active HIV control. Int. J. Cancer. 2021;149:297-306. Available from: https://doi.org/10.1002/ijc.33533

6. van Schalkwyk C, Moodley J, Welte A, Johnson LF. Modelling the impact of prevention strategies on cervical cancer incidence in South Africa. Int. J. Cancer. 2021;1-12. Available from: https://doi.org/10.1002/ijc.33716

7. Perez-Guzman PN, Chung MH, De Vuyst H, et al. The impact of scaling up cervical cancer screening and treatment services among women living with HIV in Kenya: a modelling study. BMJ Global Health. 2020;5:e001886. Available from: https://doi.org/10.1136/bmjgh-2019-001886



This article is included in the HPW Special Issue The role of modelling in informing policy and planning for prevention and control of HPV-related cancers

Scientific coordinators:
Karen Canfell, Adam Keane, Diep TN Nguyen, Michaela T Hall, James Killen, Xavier Bosch

HPW editors:
Marisa Mena, Patricia Guijarro, Paula Peremiquel

On behalf of the editorial team, we would like to thank all the authors who contributed to this special issue of HPW



OTHER ARTICLES IN THIS HPW SPECIAL ISSUE:

Interview with K Canfell

EA Burger, JJ Kim. Planning for cervical cancer elimination: The role of simulation modeling

J Berkhof. IARC Handbook on cervical cancer screening: value of this evidence synthesis for modelling

M Smith, EA Burger, I de Kok. How does COVID-19 impact cervical screening?

YL Woo, M Saville, A Keane. The road to cervical cancer elimination in Malaysia

M Jit, JJ Kim, M Brisson. Modelling one-dose HPV vaccination

N Campos, L Bruni, JJ Kim, M Schiffman. Refining health decision models to evaluate novel screening strategies in low-resource settings

I Man, I Baussano. Building resilient cancer prevention through gender-neutral HPV vaccination