The association of HPV-16 seropositivity and natural immunity to reinfection: insights from compartmental models

Abstract

Background: Seroreactivity, processes of seroconversion and seroreversion, in the context of HPV infection has been investigated in numerous studies. However, the data resulting from these studies are usually not accounted for in mathematical transmission models of various HPV types due to gaps in our understanding of the nature of seroreactivity and its implications for HPV natural history.

Methods: In this study we selected a number of simple but plausible compartmental transmission models of HPV-16, differing in assumptions regarding the relation between seropositivity and immunity, and attempted to calibrate them to Australian HPV seroprevalence data for females and males, as well as DNA prevalence data for females, using a Bayesian model comparison procedure. We ranked the models according to both their simplicity and ability to be fitted to the data.

Results: Our results demonstrate that models with seroreversion where seropositivity indicates only a partial or very short-term full protection against re-infection generate age-specific HPV DNA prevalence most consistent with the observed data when compared with other models.

Conclusions: Models supporting the notion that seropositive individuals are fully immune to reinfection demonstrated consistently inferior fits to the data than other models making no such assumption.

Figure 1

SIS models: SIS₁ (left) and SIS₂ (right); “+” and “-” denote seropositivity and seronegativity, respectively.

Figure 2

SIR models: SIR₁ (left) and SIR₂ (right); “+” and “-” denote seropositivity and seronegativity, respectively.

Figure 3

SIRS models: SIRS₁ (top left), SIRS₂ (top right), SIRS₃ (bottom left) and SIRS₄ (bottom right); “+” and “-” denote seropositivity and seronegativity, respectively.