The Creation of the Suppressive Cancer Microenvironment in Patients with HPV-Positive Cervical Cancer

Abstract

The development of malignancy is closely connected with the process of cancer microenvironment remodeling. As a malignancy develops, it stimulates the creation of the suppressive microenvironment of the tumor through the presence of cells that express membrane proteins. These proteins are secreted into the cancer microenvironment, where they enable tumor growth. In patients with cancer of the cervix, the development of the disease is also linked to high-risk HPV (hr-HPV) infection. Such infections are common, and most clear spontaneously; however, a small percentage of these infections can persist and progress into precancerous cervical intraepithelial neoplasia and invasive cervical carcinoma. Consequently, it is assumed that the presence of hr-HPV infection alone is not sufficient for the development of cancer. However, chronic HPV infection is associated with the induction of the remodeling of the microenvironment of the epithelium. Furthermore, the local microenvironment is recognized as a cofactor that participates in the persistence of the HPV infection and disease progression. This review presents the selected immune evasion mechanisms responsible for the persistence of HPV infection, beginning with the delay in the virus replication process prior to the maturation of keratinocytes, the shift to the suppressive microenvironment by a change in keratinocyte immunomodulating properties, the alteration of the Th1/Th2 polarization of the immune response in the microenvironment, and, finally, the role of HLA-G antigen expression.

Keywords: HLA-G antigen expression; cervical cancer; suppressive cancer microenvironment.