Mathematical modelling of the role of Langerhans cells in the dynamics of HPV infection.

Cervical cancer is the second most frequent gynaecological malignancy in the world. Human papillomavirus (HPV) infection is the primary etiologic agent of cervical cancer. However, HPV alone is not sufficient for tumor progression. The clinical display of HPV infection also depends on the host's immune status. Both innate and adaptive immunity recognize and fight foreign pathogens inside the body, but sometimes they prove ineffective against HPV. HPV has several mechanisms for evading the immune system. After infection, HPV multiplies in keratinocytes, which are distant from immune centers and have a naturally short lifespan. The naturally short life cycle of the keratinocyte removes the need for the virus to destroy the cells, which would trigger inflammation and immune response. In addition, HPV downregulates the expression of interferon genes. Despite viral immune evasion, the immune system effectively resists most HPV infections and mounts strong localized cell mediated immune responses. Despite significant progress in observations and clinical practice, many aspects of the complex interactions between HPV and the human immune system remain not fully understood. Langerhans cells (LCs) are known to play a critical role in producing innate and adaptive cellular immune responses against HPV infection. In this paper, we propose and analyze a mathematical of HPV infection with particular focus on the role of Langerhans cells in facilitating immune response, as well as on the treatment of HPV infection by induction of the appropriate virus-specific immune responses in patients. We determine equilibria of the model, analyse their stability, and derive the basic reproduction number. Sensitivity analysis is performed to investigate the effects of individual parameters on system dynamics. We explore the impulsive therapy for controlling HPV infection, and discuss how these findings may be helpful in development of immunotherapy against HPV infection.