An age-structured SIPC model of cervical cancer with immunotherapy

Abstract

Immunotherapy is a targeted therapy that can be applied to cervical cancer patients to prevent DNA damage caused by human papillomavirus (HPV). The HPV infects normal cervical cells withing a specific cell age interval, i.e., between the $ G_1 $ to $ S $ phase of the cell cycle. In this study, we developed a new mathematical model of age-dependent immunotherapy for cervical cancer. The model is a four-dimensional first-order partial differential equation with time- and age-independent variables. The cell population is divided into four sub-populations, i.e., susceptible cells, cells infected by HPV, precancerous cells, and cancer cells. The immunotherapy term has been added to precancerous cells since these cells can experience regression if appointed by proper treatments. The immunotherapy process is closely related to the rate of T-cell division. The treatment works in the same cell cycle that stimulates and inhibits the immune system. In our model, immunotherapy is represented as a periodic function with a small amplitude. It is based on the fluctuating interaction between T-cells and precancerous cells. We have found that there are two types of steady-state conditions, i.e., infection-free and endemic. The local and global stability of an infection-free steady-state has been analyzed based on basic reproduction numbers. We have solved the Riccati differential equation to show the existence of an endemic steady-state. The stability analysis of the endemic steady-state has been determined by using the perturbation approach and solving integral equations. Some numerical simulations are also presented in this paper to illustrate the behavior of the solutions.

Keywords

• cervical cancer
• cell dynamics
• immunotherapy
• age-structured model
• stability analysis