Although available human papillomavirus (HPV)
vaccines have high efficacy against incident
infection and disease caused by HPV types that they specifically target, new
vaccine trials continue to be needed. The goals of these trials could include change of
vaccine dose or route of administration (or both), development of second-generation
vaccines, and the regional manufacture of
biosimilar vaccines. We summarise present thinking about primary endpoints for
HPV vaccine trials as developed at an experts workshop convened by the International Agency for Research on
Cancer and the US National Cancer Institute in September, 2013. Efficacy trials that have led to licensure for
cervical cancer prevention have used the disease endpoint of
cervical intraepithelial neoplasia grade 2 or worse (CIN2+). However, on the basis of experience from the trials and present knowledge of
HPV infection, future efficacy trials for new
vaccines can be safely streamlined by the use of persistent
HPV infection, which occurs more frequently than CIN2+, and can be more reproducibly measured as a primary endpoint. Immunobridging trials can be sufficient to ascertain immunological non-inferiority for licensure for alternate dosing schedules, bridging to age 26 years or younger, and
biosimilar vaccines, with post-licensure surveillance confirming effectiveness. These recommendations are intended to help stimulate continued
vaccine development while ensuring appropriate assessment of safety and efficacy.