**7. Immune response against L1 capsid proteins**

#### **7.1. L1 positivity and clinical remission**

The immune system developed special innate and adaptive immune mechanisms to recognize and fight against foreign agents that invade our body.

Sometimes these methods are ineffective especially when the agent uses mechanisms to evade the immune system, like HPV is doing.

Since the HPV infection remains located in the epithelium, mucosal ulceration is a prerequisite for antigen contact with the immune cells in the stroma and in addition to a sufficiently high antigen dose, an efficient immune response, against HPV, also requires supporting mediators.

However, HPV itself has own characteristics also due to its route of infection that protect it from access of the immune system.

The HPV infection does not cause a systemic spreading of the infection by means of a viraemia and the infected epithelia are not destroyed. Thus, any inflammatory tissue reaction support‐ ing the immune response is suppressed, and the virus material is only released on the epithelial surface which is poor in immune defence cells and distant from immune centers.

Finally, the virus itself express only very low levels of viral protein, suppresses the release of cytokines from epithelia and intraepithelial antigen-presenting Langerhans' cells and can suppress the expression of histocompatibility antigens required for the interaction of epithelial cells and immune cells. The E7 and E6 proteins are involved in this inhibition [44], [45].

Consequently, one could envision that in this setting an efficient transfer of antigen from HPV infected keratinocytes to the antigen presenting cells (APC) is not triggered.

Nevertheless a successful immune response to genital HPV infection is established in almost all cases. But the time required for clearance of high risk types, particulary HPV16, averages 8-14 month, which is considerably longer than 5-6 months needed for clearance of low risk types [44].
