Mathematical modelling of human immunodeficiency virus and human papillomavirus disease transmission dynamics, natural history, and control interventions

Abstract

Human immunodeficiency virus (HIV) control is one of the most heavily studied diseases of our time, as an estimated 32.7 million people have lost their lives to HIV-related illnesses. The scientific community has collectively made considerable advancements in HIV prevention and treatment methods, with the implementation of programmes for voluntary medical male circumcision (VMMC), antiretroviral therapy (ART), and behavioural interventions successfully reducing HIV-related deaths globally by 60% in 2019, compared to the peak in 2004. Cervical cancer is caused by a persistent infection with an oncogenic strain of human papillomavirus (HPV), which in rare cases, facilitates the development of a lesion that progresses to cervical cancer. New evidence suggests that women living with HIV are at a six-fold greater risk of cervical cancer compared to women without HIV, as the presence of an HIV infection increases HPV infection persistence and escalates progression to cervical cancer. Cervical cancer is largely preventable through HPV vaccination and cervical screening; however, despite this, there were still over 600,000 cervical cancer cases and over 340,000 cervical cancer deaths globally in 2020. Therefore, the World Health Organisation (WHO) has called for all nations to contribute to a concerted global effort to eliminate cervical cancer as a public health problem and has launched a global strategy to accelerate this. As HIV control such as VMMC and behavioural interventions directly impact HPV transmission, and since HIV is implicated in 5% of cervical cancers, future predictions of cervical cancer incidence and mortality rates in regions with endemic HIV must account for HIV epidemic metrics and uptake of HIV control. The body of work presented in this thesis utilises a detailed model platform of HIV and HPV infection and natural history to systematically address the combined and standalone impacts of HIV and HIV control on cervical cancer incidence and mortality in Tanzania, an example country broadly representative of sub-Saharan Africa. This thesis builds on the Tanzanian example to assess the impact of the implementation and scale-up of HPV vaccination and screening for cervical cancer prevention under the WHO global strategy for cervical cancer elimination in terms of direct health benefits and cost-effectiveness and resource utilisation. The results presented in this thesis illustrate the importance of continuing to invest in sustained HIV control, which has the secondary benefit of preventing cervical cancer incidence and mortality and provides arguments for the adoption and rapid scale-up of HPV vaccination and cervical screening for all women, with particular emphasis on women living with HIV. From a broader perspective, this body of work highlights the valuable role of detailed mathematical modelling to assess population health policy.