Cervical cancer prevention in the context of abating HIV prevalence in Kenya

Gui Liu | 2021

Advisor: Ruanne Barnabas

Research Area(s): Cancer Epidemiology, Clinical Epidemiology, Global Health, Infectious Diseases

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In 2020, the World Health Organization (WHO) launched an initiative to eliminate cervical cancer as a public health problem globally. While high-income countries are expected to achieve this goal in the coming decades, the timeline for elimination will be significantly longer for lower-resourced countries with high HIV burden. In low-and-middle income countries, HIV infection is associated with a 7-fold increase in cervical cancer risk. In Kenya, where HIV prevalence among women is 6%, cervical cancer incidence rate is among the highest in the world. Further, a limited number of studies have shown that human papillomavirus (HPV) infection increases HIV risk, raising the question of whether HPV vaccination could reduce HIV burden. As the country prepares to meet the challenge of cervical cancer elimination, strategies for reducing cervical cancer burden in Kenya will need to account for the synergies between the two diseases. This dissertation aimed to comprehensively quantify the interactions between HIV infection and cervical cancer, and estimate the population-level impact of HPV vaccination on cervical cancer and HIV burden in Kenya.
Using a matched case-control study nested in a randomized control trial of HIV chemoprophylaxis, we evaluated the association between HPV infection and subsequent HIV acquisition in chapter 2. We found that HPV infections were common among both cases (women who seroconverted) and HIV-negative controls, with infection with one or more HPV types targeted by the nonavalent vaccine detected in 60% of cases and 42% of controls. Adjusting for sexual behaviors and other sexually transmitted infections, women with any HPV infection had 2.6-fold higher risk of HIV acquisition compared to women who were HPV-negative. In particular, infection with a nonavalent vaccine-targeted HPV type increased HIV risk 2.1 times and infection with a quadrivalent-vaccine-targeted type increased HIV risk 1.9 times. These findings suggest that HPV vaccination may reduce HIV incidence.
In chapter 3, we conducted a systematic review and meta-analysis to synthesize the literature on the effect of HIV infection on HPV natural history. We found that relative to HIV-negative women, women living with HIV had significantly higher risk of HPV acquisition, persistence, and progression to cervical precancerous lesions and cancer, with risks increasing as CD4 cell counts decreased. Antiretroviral therapy lowered the risk of HPV acquisition and persistence, and progression to low-grade precancerous lesions, however, its impact on high-grade lesions depended on duration of use.
Finally, in chapter 4, we evaluated the health effects of HPV vaccination in Kenya using a dynamic compartmental model that accounted for the bidirectional interactions between HPV and HIV infections. The model projected that HPV vaccination will reduce cervical cancer incidence by 68-84% and prevent 164,529-326,968 cervical cancer cases over 50 years. The impact of vaccination on cervical cancer burden was greatest and occurred earlier when women aged 15-24 were vaccinated in addition to girls aged 10-14. Further, we found that HPV vaccination will reduce HIV prevalence by 7-11%, averting 23,862-52,951 cases of HIV in men and women over 50 years. Finally, the model projected that HIV prevalence will continue to decline in Kenya, and as a result cervical cancer rates will decline even in the scenario without vaccination.
In conclusion, cervical cancer burden in Kenya can be substantially reduced with HPV vaccination; particularly if the vaccination strategy includes young women aged 15-24. While HPV vaccination had a lesser impact on HIV burden, it should be included as a component of a comprehensive HIV prevention package. Overall, our findings highlighted the importance of accounting for the changing HIV epidemiology in Kenya when considering HPV vaccination strategies.