Page 38 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman
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Chapter 2
cytokine profiles. Low grade CIN is characterized mainly by cytokines of the Th-1 profile, whereas high-grade CIN and cervical carcinoma are characterized by Th-2 profile cytokines, indicating a shift from cell-mediated to humoral immune response with increasing CIN grade.(37, 38) Finally, the cellular immune response seems to be further deregulated by regulatory T-cells. Increased frequencies and suppressive activity of these cells has been found in patients with high-grade CIN and cervical carcinoma, indicating an active downregulation of the immune response in more progressive disease.(39)
In conclusion, the development of high-grade CIN is the result of a persistent and transforming HPV infection. A subset of high-grade CIN can be cleared by the host cellular immune response (figure 4). The likelihood of spontaneous regression is determined by the balance between HPV- induced effects (deregulation of cellular processes and downregulation of the immune response) and the capacity of the host immune system.
Figure 4. Natural history of CIN in the course of time.
The development of high-grade CIN is the result of a persistent and transforming HPV infection, in which HPV- induced cell proliferation and immortalization and the accumulation of genetic instability cause histopathological abnormalities. Whereas the development of CIN is a relatively short-term process, the subsequent development of cervical carcinoma takes many years. Most low-grade lesions and a subset of high-grade CIN can be cleared by the host cellular immune response at any point of time during the infectious process, as indicated at two stages in this figure.
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