Abstract
BACKGROUND: Sexual mixing between heterogeneous population subgroups is an integral component of mathematical models of sexually transmitted infections (STIs). This study compares the fit of different mixing representations to survey data and the impact of different mixing assumptions on the predicted benefits of hypothetical human papillomavirus (HPV) vaccine strategies. METHODS: We compared novel empirical (data-driven) age mixing structures with the more commonly-used assortative-proportionate (A-P) mixing structure. The A-P mixing structure assumes that a proportion of sexual contacts - known as the assortativity constant, typically estimated from survey data or calibrated - occur exclusively within one's own age group and the remainder mixes proportionately among all age groups. The empirical age mixing structure was estimated from the National Survey on Sexual Attitudes and Lifestyles 3 (Natsal-3) using regression methods, and the assortativity constant was estimated from Natsal-3 as well. Using a simplified HPV transmission model under each mixing assumption, we calibrated the model to British HPV16 prevalence data, then estimated the reduction in steady-state prevalence and the number of infections averted due to expanding HPV vaccination from 12- through 26-year-old females alone to 12-year-old males or 27- to 39-year-old females. RESULTS: Empirical mixing provided a better fit to the Natsal-3 data than the best-fitting A-P structure. Using the model with empirical mixing as a reference, the model using the A-P structure often under- or over-estimated the benefits of vaccination, in one case overestimating by 2-fold the number of infections prevented due to extended female catch-up in a high vaccine uptake setting. CONCLUSIONS: An empirical mixing structure more accurately represents sexual mixing survey data, and using the less accurate, yet commonly-used A-P structure has a notable effect on estimates of HPV vaccination benefits. This underscores the need for mixing structures that are less dependent on unverified assumptions and are directly informed by sexual behavior data.