Within host dynamics of HPV infection with cellular immunity and HPV-infected dormant cells reactivation

Abstract

Like other viruses, human papillomavirus genotypes can remain dormant for years or decades and later reactivate due to some well-known factors. The activation of such a dormant infection years later can cause many health and behavioural problems at the individual and societal levels, respectively. From a personalised health perspective, reactivation of a dormant HPV, especially high-risk genotypes such as HPV 16 or 18 can worsen the health condition of the infected person, should they be (or happen to be newly) infected with a different HPV genotype. However, detailed mechanisms that impact the health outcome of an infected person due to rebounding dormant HPV have not been mathematically investigated. The core of this paper is to study the dynamics of an in-host high-risk HPV infection, taking into account cell-mediated immunity and the consequences of reactivation of HPV-infected dormant cells using compartmental modelling. The local and global stabilities of the equilibria are established using Lyapunov and LaSalle techniques, and the bifurcation analysis is performed. Compared to the model without the provision of virus particles due to the reactivation of infected dormant cells, our results suggest that such reactivation can exacerbate the health condition of an infected person by promoting the persistence of infection, which further weakens the active immune response and favours the progression of infection to HPV-induced cancers. In addition, we provide the sensitivity analysis of threshold parameters, state variables with respect to model parameters, and numerical simulations are used to illustrate the theoretical results.