Comparison of the immunogenicity and safety of Cervarix™ and Gardasil® human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18-45 years

This observer-blind study compared the prophylactic human papillomavirus (HPV) vaccines, Cervarix™ (GlaxoSmithKline) and Gardasil® (Merck), by assessing immunogenicity and safety through one month after completion of the three-dose vaccination course. Women (n = 1106) were stratified by age (18-26, 27-35, 36-45 years) and randomized (1:1) to receive Cervarix™ (Months 0, 1, 6) or Gardasil® (Months 0, 2, 6). At Month 7 after first vaccination, all women in the according-toprotocol cohort who were seronegative/DNA negative before vaccination for the HPV type analyzed had seroconverted for HPV-16 and HPV-18 serum neutralizing antibodies, as measured by pseudovirion-based neutralization assay (PBNA), except for two women aged 27-35 years in the Gardasil® group who did not seroconvert for HPV-18 (98%). Geometric mean titers of serum neutralizing antibodies ranged from 2.3-4.8-fold higher for HPV-16 and 6.8-9.1-fold higher for HPV-18 after vaccination with Cervarix™ compared with Gardasil®, across all age strata. In the total vaccinated cohort (all women who received at least one vaccine dose, regardless of their serological and DNA status prior to vaccination), Cervarix™ induced significantly higher serum neutralizing antibody titers in all age strata (p < 0.0001). Positivity rates for anti-HPV-16 and -18 neutralizing antibodies in cervicovaginal secretions and circulating HPV-16 and -18 specific memory B-cell frequencies were also higher after vaccination with Cervarix™ compared with Gardasil ®. Both vaccines were generally well tolerated. The incidence of unsolicited adverse events was comparable between vaccinated groups. The incidence of solicited symptoms was generally higher after Cervarix™, injection site reactions being most common. However, compliance rates with the three-dose schedules were similarly high (≥ 84%) for both vaccines. Although the importance of differences in magnitude of immune response between these vaccines is unknown, they may represent determinants of duration of protection against HPV-16/18. Long-term studies evaluating duration of efficacy after vaccination are needed for both vaccines.