TY - JOUR
T1 - Primary endpoints for future prophylactic human papillomavirus vaccine trials
T2 - Towards infection and immunobridging
AU - for the Participants in the IARC/NCI workshop on Primary Endpoints for Prophylactic HPV Vaccine Trials
AU - Lowy, Douglas R.
AU - Herrero, Rolando
AU - Hildesheim, Allan
AU - Cuzick, Jack
AU - de Sanjose Llongueras, Silvia
AU - Dillner, Joakim
AU - Franceschi, Silvia
AU - Eduardo L Franco, L Franco
AU - Garland, Suzanne
AU - Gillison, Maura
AU - Giuliano, Anna R.
AU - Lehtinen, Matti
AU - Paavonen, Jorma
AU - Palefsky, Joel
AU - Schiffman, Mark
AU - Schiller, John T.
AU - Stanley, Margaret
AU - Wheeler, Cosette M.
N1 - Funding Information:
This Series paper was borne out of the International Agency for Research on Cancer and the US National Cancer Institute workshop on Primary Endpoints for Prophylactic HPV Vaccine Trials. We thank Gary Clifford, Linda Eckert, Aimee Kreimer, Suzanne Kruger-Kjaer, Lauri Markowitz, Pieter Neels, Martyn Plummer, Jeff Roberts, Rengaswamy Sankaranarayanan, Mahboobeh Safaeian, Vivien Davis Tsu, Elizabeth R Unger, Salvatore Vaccarella, Sholom Wacholder, and Christopher Wild. DRL and AH are employed by the National Cancer Institute, National Institutes of Health. This Series paper is supported in part by the Intramural Research Program, National Cancer Institute, National Institutes of Health.
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84933533810&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84933533810&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(15)70075-6
DO - 10.1016/S1470-2045(15)70075-6
M3 - Review article
C2 - 25943067
AN - SCOPUS:84933533810
SN - 1470-2045
VL - 16
SP - e226-e233
JO - The lancet oncology
JF - The lancet oncology
IS - 5
ER -