The Role of Acquired Immunity in the Spread of Human Papillomavirus (HPV): Explorations with a Microsimulation Model

BACKGROUND Knowledge of the natural history of human papillomavirus (HPV), in particular the role of immunity, is crucial in estimating the (cost-) effectiveness of HPV vaccination and cervical cancer screening strategies, because naturally acquired immunity after clearing an infection may already protect part of the risk population against new HPV infections. METHODS We used STDSIM, an established stochastic microsimulation model, quantified to the Netherlands. We explored different assumptions regarding the natural history of HPV-16 and HPV-18, and estimated the transmission probabilities and durations of acquired immunity necessary to reproduce age-specific prevalence. RESULTS A model without acquired immunity cannot reproduce the age-specific patterns of HPV. Also, it is necessary to assume a high degree of individual variation in the duration of infection and acquired immunity. According to the model estimates, on average 20% of women are immune for HPV-16 and 15% for HPV-18. After an HPV-16 infection, 50% are immune for less than 1 year, whereas 20% exceed 30 years. For HPV-18, up to 12% of the individuals are immune for less than 1 year, and about 50% over 30 years. Almost half of all women will never acquire HPV-16 or HPV-18. CONCLUSIONS Acquired immunity likely plays a major role in HPV epidemiology, but its duration shows substantial variation. Combined with the lifetime risk, this explains to a large extent why many women will never develop cervical cancer.