Immunogenicity, Reactogenicity, and Safety of Human Papillomavirus 16/18 AS04-Adjuvanted Vaccine in Japanese Women

Abstract

A phase II, double-blind, controlled randomized multicenter study with human papillomavirus (HPV) 16/18 AS04 (3-O-desacyl-4'-monophosphoryl lipid A and aluminum hydroxide)-adjuvanted vaccine is ongoing in Japanese women aged 20 to 25 years. An interim analysis was performed at month 7 (1 month after the third dose of vaccine) to determine reactogenicity, safety, and immunogenicity of the vaccine and to evaluate the baseline HPV-16/18 seropositivity and DNA status of women. In the HPV-16/18 group (according-to-protocol cohort for immunogenicity analysis), 100% seroconversion was observed against HPV-16 and HPV-18 at month 6 (5 months after the second dose) and at month 7. At month 7, anti-HPV-16 geometric mean titer (GMT) was 7441.0 enzyme-linked immunosorbent assay units/mL and anti-HPV-18 GMT was 3805.4 enzyme-linked immunosorbent assay units/mL, which is, respectively, 250- and 168-fold higher than GMTs observed after natural infection with HPV-16 or HPV-18. In the total vaccinated cohort, the seropositivity rates against HPV-16 and HPV-18 at study entry were 17.3% and 15.8%, respectively. At the same time point, HPV-16 and HPV-18 DNA was detected in 6.5% and 4.0% of the women, respectively. The immunogenicity of the HPV-16/18 vaccine and the HPV prevalence before vaccination in Japanese women are in line with what was observed in other populations. Injection site symptoms and some general symptoms were reported more frequently in the HPV-16/18 group than in the hepatitis A vaccine group but had no impact on compliance with completion of the vaccination course. Overall, the HPV-16/18 vaccine had a good safety profile, was well tolerated, and is highly immunogenic in the study population of Japanese women.

Immunogenicity and safety of human papillomavirus (HPV) vaccination in Asian populations from six countries: a meta-analysis

“…1. Finally, 10 articles were considered (30)(31)(32)(33)(34)(35)(36)(37)(38)(39) in the systematic review and meta-analysis.…”

“…Clinical trials on HPV vaccination in Asia were performed in six different countries (Korea, Japan, India, China, Bangladesh and Malaysia) and funded by three different companies: Merck, GlaxoSmithKline (GSK), and Grameenphone (the first two in pharmaceuticals, the latter in telecommunication). Most of the studies (N = 7) provided their clinical trial registration numbers (31)(32)(33)(34)(35)38,39). In addition, almost all studies (N = 9) included only women (30)(31)(32)(33)(34)(35)(36)38,39).…”

“…Both HPV vaccines were investigated in the 10 different trials: the bivalent vaccine from GSK (containing HPV types 16 and 18) in eight trials (31)(32)(33)(34)(35)(36)38,39) and the quadrivalent vaccine from Merck (containing HPV types 6, 11, 16 and 18) in two trials (30,37). The majority of the studies included placebo as the comparator (30,(33)(34)(35)(36)(37)(38)(39); two studies on the bivalent vaccine used the Hepatitis A virus vaccine as comparator (31,32). The number of persons included in most of the studies was less than 1000, but one study in China included 6051 persons, and investigated not only immunogenicity and safety of the vaccine but also vaccine efficacy on the prevention of 6-months persistence of infection and CIN associated with HPV16 and/or HPV18 infection (39).…”

“…Studies with the bivalent vaccine implemented administration schedules of 0, 1 and 6 months in the trial (31)(32)(33)(34)(35)(36)38,39), while studies with the quadrivalent vaccine implemented an administration schedule of 0, 2 and 6 (30,37). Although almost all studies performed immunogenicity testing at 7 months in the trial, there was one study that performed more extensive immunogenicity testing at 7, 12, 14, 36 and 48 months, with the primary endpoint of the latter study being assessment of vaccine efficacy with respect to prevention of 6-months persistent infection and/or histopatologically confirmed CIN associated with HPV16 and/or HPV18 (39).…”

Role of HPV Vaccination in Fighting Cervical Cancer

“…As in June of 2013, the Japanese Ministry of Health partially suspended its HPV vaccination program (3) due to an adverse reaction from the vaccines. A study done by Japan reported that there were reactions from mild symptoms such as pain, redness and swelling at the injection site to serious adverse events such as brain contusion, skull fracture and appendicitis (18) . The study also reported one spontaneous abortion possibly related to vaccination which occurred 2 weeks after the vaccination.…”