Immune responses against virus and tumor in cervical carcinogenesis: treatment strategies for avoiding the HPV-induced immune escape.

Despite the availability of prophylactic vaccines against human papillomavirus (HPV), cervical cancer (CC) is still a major problem globally. It is the cancer with the second highest incidence and the third highest mortality in women worldwide, but, in less developed countries, it is an even greater problem being the second most common cause of cancer death. Although HPV infection is one of the most common sexually transmitted diseases, and high-risk HPV16 is the most frequent genotype involved, only a small number of HPV-infected women develop high-grade squamous intraepithelial lesions whereas, in the remainder of the women, the virus disappears spontaneously. There is a lot of evidence to support the view that host-dependent immunologic status and HPV-induced immune evasion are responsible for persistent HPV infection and subsequent development of cervical neoplasia. Therefore, the role of the immune system, not only in viral clearance but also in tumor antigen recognition, is particularly relevant in the case of cervical carcinogenesis. A better understanding of these processes would help in the development of therapeutic vaccines. This review aims to explain which immune cells and molecules are involved in the process of viral and tumor recognition, how their failure can lead to cervical carcinoma and what are the main therapeutic strategies so far tested in preclinical models and clinical trials to stimulate the immune system in cervical carcinoma.