HPV-16 viral load in association with cervical neoplasia and cancer in Senegal
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<bold>Background</bold>: The importance of certain characteristics of human papillomavirus (HPV) infection and human immunodeficiency virus (HIV) infection in the pathogenesis of cervical cancer has not yet been established. Although infection with HPV is a necessary cause of cervical cancer and its precursor lesions, cervical intraepithelial neoplasia (CIN), the exact role of HPV type-specific infection and HPV DNA concentration (viral load) in cervical disease development remains unclear. Furthermore, data are lacking regarding the association between HPV infection, human immunodeficiency virus (HIV) infection, and HIV-induced immunosuppression. This dissertation examines the role of HPV-16 viral load in the development of CIN and cervical cancer among women from Senegal, West Africa. In addition, the relationship between overall and type-specific HPV detection, HIV infection and immunosuppression is investigated. <bold>Methods</bold>: Three major strategies are used to investigate these research questions: 1) A cross-sectional analysis of HPV type 16 viral load in relation to severity of cervical disease, 2) A longitudinal analysis of baseline HPV type 16 viral load in relation to future clearance of infection and development of CIN or cancer, and 3) An historical cross-sectional analysis of HPV DNA detection among HIV-positive and HIV-negative women, by immune status. <bold>Results</bold>: Compared to women with no cervical disease, HPV-16 viral loads were increased in women with CIN and invasive cancer. Longitudinally, HPV-16 viral load was inversely associated with clearance of HPV-16 infection and marginally associated with development of CIN or worse. The prevalence of HPV DNA was greater among HIV-positive compared to HIV-negative women. This trend was also seen for HPV types 16 and 18, which are responsible for the majority of cervical cancer. In addition, HIV-infected women with severe immunodepression were at increased risk of overall and type-specific HPV infection. <bold>Conclusions</bold>: HPV-16 viral loads may be useful correlates of existing disease severity and of development of adverse HPV infection outcomes, including viral persistence and CIN. Measures to prevent initial HPV infection and subsequent development of cervical cancer should be emphasized in high risk populations, especially among HIV-positive women. Further studies are needed to clarify the role of HPV viral load in the natural history of HPV infection.
- Epidemiology