Impact of human papillomavirus age-related prevalence and vaccination levels on interpretation of cervical screening modalities: a modelling study

Objective Cervical screening is a life-saving intervention, which reduces the incidence of and mortality from cervical cancer in the population. Human papillomavirus (HPV) based screening modalities hold unique promise in improving screening accuracy. HPV prevalence varies markedly by age, as does resultant cervical intraepithelial neoplasia (CIN), with higher rates recorded in younger women. With the advent of effective vaccination for HPV drastically reducing prevalence of both HPV and CIN, it is critical to model how the accuracy of different screening approaches varies with age cohort and vaccination status. This work establishes a model for the age-specific prevalence of HPV factoring in vaccine coverage and predicts how the accuracy of common screening modalities is affected by age profile and vaccine uptake.Design Modelling study of HPV infection rates by age, ascertained from European cohorts prior to the introduction of vaccination. Reductions in HPV due to vaccination were estimated from the bounds predicted from multiple modelling studies, yielding a model for age-varying HPV and CIN grades 2 and above (CIN2+) prevalence.Setting Performance of both conventional liquid-based cytology (LBC) screening and HPV screening with LBC reflex (HPV reflex) was estimated under different simulated age cohorts and vaccination levels.Participants Simulated populations of varying age and vaccination status.Results HPV-reflex modalities consistently result in much lower incidence of false positives than LBC testing, with an accuracy that improves even as HPV and CIN2+ rates decline.Conclusions HPV-reflex tests outperform LBC tests across all age profiles, resulting in greater test accuracy. This improvement is especially pronounced as HPV infection rates fall and suggests HPV-reflex modalities are robust to future changes in the epidemiology of HPV.