Abstract
Quantifying rates governing the clearance of Human Papillomavirus (HPV) and its progression to clinical disease, together with viral transmissibility and the duration of naturally-acquired immunity, is essential in estimating the impact of vaccination programmes and screening or testing regimes. However, the complex natural history of HPV makes this difficult. We infer the viral transmissibility, rate of waning natural immunity and rates of progression and clearance of infection of 13 high-risk and 2 non-oncogenic HPV types, making use of a number of rich datasets from Sweden. Estimates of viral transmissibility, clearance of initial infection and waning immunity were derived in a Bayesian framework by fitting a susceptible-infectious-recovered-susceptible (SIRS) transmission model to age- and type-specific HPV prevalence data from both a cross-sectional study and a randomised controlled trial (RCT) of primary HPV screening. The models fitted well, but over-estimated the prevalence of four high-risk types with respect to the data. Three of these types (HPV-33, -35 and -58) are among the most closely related phylogenetically to the most prevalent HPV-16. The fourth (HPV-45) is the most closely related to HPV-18; the second most prevalent type. We suggest that this may be an indicator of cross-immunity. Rates of progression and clearance of clinical lesions were additionally estimated from longitudinal data gathered as part of the same RCT. Our estimates of progression and clearance rates are consistent with the findings of survival analysis studies and we extend the literature by estimating progression and clearance rates for non-16 and non-18 high-risk types. We anticipate that such type-specific estimates will be useful in the parameterisation of further models and in developing our understanding of HPV natural history.
Highlights
Persistent infection with high-risk human papillomavirus (HPV) has been shown to be the necessary precursor of progression to cervical cancer [1,2,3]
The prevalence of HPV-16 infection in women taking part in the Swedescreen trial was higher than those of the same age (32–38) attending Chlamydia testing, HPV-18 and HPV-33 were observed at closely comparable levels in both studies but all other high-risk types were less prevalent in the former group
We have made estimates for the transmissibility, clearance and progression rates and rates of waning natural immunity for 13 high-risk types of HPV by using Swedish behavioural and epidemiological data to fit an ensemble of deterministic models of HPV transmission and progression
Summary
Persistent infection with high-risk human papillomavirus (HPV) has been shown to be the necessary precursor of progression to cervical cancer [1,2,3]. Kim et al [20], Van de Velde [21] and Jit et al [5] have evaluated the goodness of fit between model output and observed data for a wide range of possible model structures and systematically chosen parameter values and Bogaards et al [22] have applied Markov Chain Monte Carlo (MCMC) techniques to characterise posterior distributions for the rates of transmissibility and waning natural immunity of 14 highrisk HPV types These developments have allowed the beginnings of quantitative understanding of both the uncertainty and sensitivity of HPV natural history parameters. Such an insight is crucial to confident predictions of vaccination or screening programme effectiveness
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
