The development of the 9vHPV vaccine represents the culmination of over 20 years of continuous HPV vaccine research & development. After the demonstration by several research groups that HPV L1 capsid protein expressed in a recombinant system forms VLPs, studies showed that VLPs can be disassembled and reassembled into more stable and immunogenic structures, which enabled commercial development. Proof-of-concept studies in animal models and the identification by IARC of HPV 16 and 18 as carcinogenic was followed by clinical development in 1997 using proof-of-principle studies of monovalent vaccines. The qHPV vaccine was evaluated beginning in 2000 as a 3-dose series in young women age 16-26 years and prevented HPV16/18-related cervical, vulvar, and vaginal high-grade dysplasia and HPV6/11-related genital warts. In 2004, efficacy studies of the qHPV vaccine administered as a 3-dose regimen were initiated in mid-adult women age 24-45 years and young men age 16-26 years; the qHPV vaccine prevented HPV6/11/16/18-related infection and cervical, vulvar, and vaginal dysplasia in mid-adult women; it also prevented HPV6/11/16/16-related anal dysplasia and genital warts in young men. Efficacy results of qHPV vaccine in young women and young men were extrapolated to pre- and young adolescent girls and boys based on the demonstration of non-inferior immunogenicity compared with women or men. It also became known in 2004 that HPV31/33/45/52/58 were the next most frequent types associated with cervical cancer; thus, a preliminary Phase II immunogenicity study was started in 2005 to identify a higher-valent HPV vaccine candidate. The 9vHPV vaccine was evaluated beginning in 2007 in over 14,000 young women age 16-26 years. Efficacy results in young women were extrapolated to girls, boys and young men based on the demonstration of non-inferior immunogenicity. A study of a 2-dose schedule in girls and boys age 9-14 years was initiated in 2013 and is expected to be completed in 2017. The bivalent HPV vaccine was developed in girls and women along similar timelines as the qHPV vaccine. The qHPV, bivalent HPV, and 9vHPV vaccines were first licensed in 2006, 2007 and 2014, respectively.
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