A 9-Valent HPV Vaccine Against Infection and Intraepithelial Neoplasia in Women

Abstract

BACKGROUNDThe investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age. METHODSWe performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV. RESULTSThe rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to 33,45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to 11,16,and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group. CONCLUSIONSThe 9vHPV vaccine prevented infection and disease related to 33,45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).

Public health value of universal HPV vaccination

“…In a total of 14,215 randomized participants population the 9vHPV vaccine has been studied: this study showed that the 9vHPV vaccine prevented cervical, vulvar, and vaginal disease and persistent infection associated with HPV-31,-33,-45,-52, and-58, and generated antibody response to HPV-6,-11,-16, and-18 that was not inferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine (20).…”

HPV Infection and Cervical Abnormalities in HIV Positive Women in Different Regions of Brazil, a Middle-Income Country

“…When compared to the quadrivalent HPV vaccine, the 9-valent vaccine prevented infection and disease specifically related to HPV -31, -33, -45, -52 and -58, and generated an equivalent antibody response to . This vaccine also holds the potential of markedly decreasing the incidence of abnormal cervical cytology and associated diagnostic and therapeutic procedures (Joura et al, 2015). This vaccine has the very high potential of markedly reducing the incidence of HPV-related pre-cancers and cancers when given at appropriate vaccination thresholds, which can contribute greatly to controlling cervical cancer in HIV+ women.…”

“…At appropriate vaccination thresholds, this vaccine may have a tremendous impact on screening as well, with a legitimate rationale for increasing screening intervals given the anticipated decrease in the disease burden. Furthermore, understanding the specific prevalence and distribution of HPV genotypes in different geographic locations will help yield further insight into whether this new vaccine holds any promise and value (Joura et al, 2015).…”

Clinicopathologic Features Associated With Human Papillomavirus/p16 in Patients With Metastatic Squamous Cell Carcinoma of the Anal Canal

“…Although advocated by the Centers for Disease Control and Prevention and the National Cancer Institute, the HPV quadrivalent and bivalent vaccine is largely underused in the U.S. in children, adolescents, and young adults [47]. The Food and Drug Administration has recently approved the nonavalent vaccine [48]. Its use will capture additional subtypes of HPV.…”