Page 36 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

Chapter 2
individuals in which HPV infections and CIN will and will not persist. An important viral factor is the individual oncogenic potential of different HPV types, which is determined by differences in interactions with cellular functions after infection. For example, the affinity of E6 and E7 for p53 and pRb is lower for low risk-HPV types than for high-risk HPV types. Other important viral and host factors influence the ability of the infected individual to clear HPV infection or HPV-induced CIN lesions. These include the ability of HPV to evade and down regulate the host immune system and also the individual capacity of the host immune system for clearance of HPV and CIN lesions. Genetic differences in immune capacity, acquired immunodeficiency and other factors such as smoking may lead to an increased or decreased individual ability for clearance.
Figure 3. Interaction between virus and host in the natural history of high-grade CIN.
The natural history of high-grade CIN is influenced by a complex interaction between viral and host factors. The most important established viral factor is the HPV genotype, determining the viral oncogenic potential. Host factors include factors which influence the individual immune capacity, such as genetic differences in immune capacity and acquired immunodeficiency. The attributing role of the immune response in the natural history of HPV infection and CIN lesions will be reviewed hereafter.
Immune response
The immune response to HPV infection has been extensively reviewed by other authors.(34, 35) An overview of important immunological mechanisms will be provided here as a basis for biomarker selection.
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