Practice of Epidemiology Epidemiologic Approaches to Evaluating the Potential for Human Papillomavirus Type Replacement Postvaccination

Currently, 2 vaccines exist that prevent infection by the genotypes of human papillomavirus (HPV) responsible for approximately 70 % of cervical cancer cases worldwide. Although vaccination is expected to reduce the preva-lence of these HPV types, there is concern about the effect this could have on the distribution of other oncogenic types. According to basic ecological principles, if competition exists between ≥2 different HPV types for niche occupation during natural infection, elimination of 1 type may lead to an increase in other type(s). Here, we discuss this issue of “type replacement ” and present different epidemiologic approaches for evaluation of HPV type competition. Briefly, these approaches involve: 1) calculation of the expected frequency of coinfection under independence between HPV types for comparison with observed frequency; 2) construction of hierarchical logistic regression models for each vaccine-targeted type; and 3) construction of Kaplan-Meier curves and Cox models to evaluate sequential acquisition and clearance of HPV types according to baseline HPV status. We also discuss a related issue concerning diagnostic artifacts arising when multiple HPV types are present in specific samples (due to the inability of broad-spectrum assays to detect certain types present in lower concentrations). This may result in an apparent increase in previously undetected types postvaccination. cervical cancer; human papillomavirus; HPV type replacement; vaccination Abbreviations: CI, confidence interval; E, expected; HPV, human papillomavirus; O, observed; PCR, polymerase chain reaction