HPV Type Replacement After HPV Vaccination

Human papillomavirus (HPV) vaccination effectively reduces the risk of HPV-attributable cancers, including cervical, vulvar, vaginal, anal, oropharyngeal, and other head and neck cancers. Concerns for a lower-than-expected vaccine impact, as defined as an increase in the prevalence of precancer by nonvaccine types, compared to that anticipated based on attribution studies, have been raised in the postvaccination era. Three distinct and nonmutually exclusive processes-HPV type replacement, clinical unmasking, and viral unmasking-could be responsible for this apparent increase of nonvaccine types. HPV type replacement, in which nonvaccine types fill a niche left vacant after the elimination of vaccine types, is unlikely to occur due to the remarkable genetic stability of the virus and the lack of natural competition between individual HPV types. However, clinical unmasking, in which the absence of clinical interventions aimed at eliminating cervical disease caused by vaccine types permits uninterrupted progression of nonvaccine types, may occur since HPV coinfections are common. Alternatively, the observed shift could be completely erroneous due to the false discovery of type replacement via viral unmasking, a diagnostic assay artifact. In this chapter, we describe these processes and the mechanisms underlying them.