Could the human papillomavirus vaccines drive virulence evolution?

Abstract

The human papillomavirus (HPV) vaccines hold great promise for preventing several cancers caused by HPV infections. Yet little attention has been given to whether HPV could respond evolutionarily to the new selection pressures imposed on it by the novel immunity response created by the vaccine. Here, we present and theoretically validate a mechanism by which the vaccine alters the transmission-recovery trade-off that constrains HPV's virulence such that higher oncogene expression is favoured. With a high oncogene expression strategy, the virus is able to increase its viral load and infected cell population before clearance by the vaccine, thus improving its chances of transmission. This new rapid cell-proliferation strategy is able to circulate between hosts with medium to high turnover rates of sexual partners. We also discuss the importance of better quantifying the duration of challenge infections and the degree to which a vaccinated host can shed virus. The generality of the models presented here suggests a wider applicability of this mechanism, and thus highlights the need to investigate viral oncogenicity from an evolutionary perspective.

Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa

“…We model HPV in-host dynamics as in [23]. We consider the interaction between four populations: i) HPV infected basal epithelial cells ( Y 1 ), ii) the HPV infected transit-amplifying cells, in the suprabasal epithelial layer ( Y 2 ), iii) HPV ( W) and iv) HPV-specific cytotoxic T lymphocytes (CTL) ( E) .…”

“…The Y 2 cells become transit-amplifying cells which start assembling virions to be released at the surface [29, 30]. Therefore, both Y 1 and Y 2 cells are HPV infected cells but differentially located in the epithelial cell layer, wherein Y 2 cells are assumed to have higher expression of the oncogenes E6 and E7 compared to Y 1 [23]. For simplification, we assume that the uninfected cells and infected cells have an equal probability of interaction with the HPV virions irrespective of the spatial architecture of the tissue.…”

“…Due to higher expression of oncogenes, the transit-amplifying cells, Y 2 divide more before death, compared to the basal infected cells Y 1 . Since, both infected cell population have an expression of oncogene, as in [23], both types of infected cells produce free virions ( W) , at production rates k 1 and k 2 , that are released through bursting. For simplicity, we consider an equal virion production rate of k 1 = k 2 = k .…”

“…Building on previous models of HIV [22] and HPV [23] single infections, this novel model captures the molecular interactions between HIV and HPV due to tat and the effect of progressive depletion of CD4+ T cell due to HIV infection. Using the model, we aim to investigate why the prevalence of oral HPV infection is increased in HIV-infected individuals.…”

Combined SYBR Green real-time polymerase chain reaction and microarray method for the simultaneous determination of human papillomavirus loads and genotypes

“…Evaluation of both viral load and HPV type in cervical cancer screening is thought to be helpful for prediction of HPV persistence and cervical carcinogenesis, and for proper management of women who have HPV infections. Furthermore, evaluation of HPV type is important for monitoring the impact of the vaccines that protect against a limited number of genotypes [161718]. For therapeutic vaccines under development, HPV typing will be important to determine the elimination of a specific virus type [19].…”