Regulation of Inflammatory Pathways in Cancer and Infectious Disease of the Cervix

Figure 1

HIV infects cells and the tat protein causes the amplification of the HPV E1/L1 genes leading to increased HPV replication and release of HPV virions. These then infect the same or adjacent cervical epithelial cell. Within the epithelial cells, the HPV E6 oncoprotein binds to P53 protein targeting it for ubiquitin-dependent degradation while the E7 binds to the Rb protein thus disrupting the Rb and E2F complex and can increase nitric oxide (NO) production, DNA damage and the activation of the COX-2/PG/PG receptor inflammatory pathways leading to increased inflammation and tumorigenesis. Inflammatory and tumor cells can then release cytokines, chemokines and PG which act in autocrine/paracrine to regulate the endothelial, stromal, neoplastic epithelial and infiltrating immune cells function to cause an increased tumour angiogenesis, increased tumour growth, decreased apoptosis, and decreased local immune-surveillance. These conditions favour tumorigenesis and viral survival in the tumor microenvironment. Inhibition of the COX-PG cascade with nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin could reduce inflammation and tumour progression by inhibiting downstream pathways activated by PG and promote proresolution by elevating expression of resolution lipid mediators such as Resolvins.