Figure 4.

Schematic representation of the role of Fas and FasL in CC progression. The main event in human papillomavirus (HPV)-induced carcinogenesis is the infection of cervical epithelial cells at the basement membrane. Upon infection, an average of 2–3 years are required to develop L-SIL and H-SIL. The immune system plays a key role in HPV-induced carcinogenesis, since more than 90% of high-risk HPV infections regress, as well as most of the low-grade lesions (75%). The long period of time between the viral infection and the development of an invasive disease implies a failed immune response, crucial for cancer progression. A) Upon HPV infection, Fas and FasL are overexpressed at the systemic level, on the surface of immune cells, and in the serum of L-SIL patients, possibly derived from activated lymphocytes in response to HR-HPV infection. B) FasL levels are increased in cervical cancer cells in correspondence with the lesion grade, with the highest concentrations measured in cancer patients. This may lead to release of FasL from cervical cancer cells, which interacts with the Fas receptor on the surface of T lymphocytes, probably inducing apoptosis. C) These events are key for the impairment of immune responses allowing the persistence of HPV and eventually results in cell transformation