Shepherd, Leah; (2017) The evolving epidemiology and emerging biomarkers of cancers in the HIV positive populations. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Effective and durable HIV treatment and increased longevity of HIV-positive (HIV+) people [1-6] has led to a growing burden of cancers in this population [7-9]. The aims of this thesis were to describe the changing epidemiology of commonly occurring cancers in HIV+ people (with a focus on Europe) and to explore and characterise plasma biomarkers of common cancers in HIV+ people. Results showed that the incidence of infection unrelated cancers are not declining in HIV+ people, primarily driven by aging of the HIV+ population and higher prevalence of cancer risk factors such as smoking. Smoking presents as one of the few modifiable cancer risk factors which can be targeted to reduce burden. Although smoking cessation quickly reduces the incidence of many smoking related cancers, the incidence of lung cancer remains at a similar level to current smokers ≥5 years after cessation. Risk factors for non-Hodgkin (NHL) and Hodgkin lymphoma (HL) differ, with HL primarily driven by low CD4 cell counts, whereas NHL is driven by a combination of immune deficiency and other HIV-mediated immune dysfunction. Furthermore, markers of immune activation are elevated ≥2 years prior to lymphoma diagnosis and are correlated with high level of HIV viremia. Levels of prostate specific antigen (PSA) were raised and increasing many years prior to prostate cancer diagnosis, however, use of the cut off of PSA >4 ng/mL to identify men at high risk of prostate cancer may not be appropriate in HIV+ men due to lower levels of circulating PSA. In conclusion, the results of this thesis provide evidence to advise and improve the care of aging HIV+ people at elevated risk for cancers through the identification and characterisation of risk factors for common cancers, investigating possible mechanisms driving cancer genesis, and assessing the usefulness of commonly used diagnostic practices.

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