Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24–45 years: a randomised, double-blind trial

The humoral response to Gardasil over four years as defined by Total IgG and competitive Luminex immunoassay

“…[30][31][32][33] Correspondingly, a high level of vaccine efficacy, for the quadrivalent vaccine, has been demonstrated against infection and disease caused by HPV types 6, 11, 16 and 18. [1][2][3][4][5]34 Although an immune correlate of protection against HPV infection has not yet been established, understanding the limitations and benefits of various immunoassays will help inform and refine immunogenicity studies and shed light on the current tools, the ability of the current immunoassays, to distinguish an immune correlate of protection if breakthrough cases should be observed in the future.…”

Recommended immunization schedules for adults: Clinical practice guidelines by the Escmid Vaccine Study Group (EVASG), European Geriatric Medicine Society (EUGMS) and the World Association for Infectious Diseases and Immunological Disorders (WAidid)

“…37 The end-of-study results of a phase III efficacy, safety, and immunogenicity study involving the quadrivalent vaccine in women aged 24-45 y reported a vaccine efficacy against disease or infection related to HPV 6,11,16, and 18 in the accordingto-protocol (ATP) population of 88.7% (95% CI: 78.1, 94.8), and 66.9% (95% CI: 4.3, 90.6) in the intention-to-treat population (ITT), i.e., women who were seropositive and DNA negative for the HPV vaccine type at the time of enrolment, who received at least one dose of the vaccine. 38 In the intermediate analysis of this study, Munoz et al 39 reported a 30.9% (95% CI 11.1-46.5) efficacy of the quadrivalent vaccine against disease or infection related to HPV 6/11/16/18 in the ITT population, here including women aged 24-45 y with infection or disease present at baseline. This low percentage, with reference to the 90.5% (95% CI 73.7-97.5) efficacy observed in the ATP population, confirms that HPV vaccines are most effective when administered before exposure to HPV because they have no therapeutic effect and can only protect against HPV types not already acquired at the time of vaccination.…”

“…40 However, most HPV-positive women included in this study were positive to only one HPV genotype at enrollment, and could therefore still potentially benefit from the HPV vaccine genotypes with which they were not yet infected. 39 A follow-up of the phase III efficacy, safety, and immunogenicity study involving the bivalent vaccine in women older than 25 y has recently been published and reported a vaccine efficacy against persistent HPV 16/18 -related infection and CIN1C of 81.1% (97.7% CI 52.1-91.0) in the ATP cohort. This study included a subset of women with a history of HPV infection or disease, and as such, supported the contention that women older than 25 y can also benefit from HPV vaccination when they have been previously exposed to HPV.…”

EUROGIN 2008 roadmap on cervical cancer prevention

“…Therefore, the group of older, sexually active women includes many who have been previously exposed, with a corresponding reduction of the potential impact of the vaccine in this group. ATP analyses in these age groups indicate efficacy among apparently unexposed women as shown by Muñoz et al 15 but the proper evaluation of the potential utility of HPV vaccines at older ages would require efficacy and effectiveness analysis of large numbers of women (many thousands) to take into account the decreasing fraction of subjects in that age group who may still benefit from the prophylactic effect against CIN21.…”

“…1 Data from the quadrivalent vaccine trial also suggested excellent protection from developing incident HPV infection and low-grade cervical and external genitalia lesions associated with HPV vaccine types in women not previously infected with these HPV types but neither prevention of CIN21 nor significant reductions in persistent HPV 16 or 18 infections were reported in the intent to treat analyses. 15 In fact, current vaccine trials of women above age 26 years may well be too small to assess these endpoints, owing to the rare occurrence of CIN21 in ''older'' women who have never been infected with HPV16 or 18. Whereas immunobridging studies were used to compare the antibody levels of girls younger than 15 years to those of older females included in clinical efficacy trials of precancerous and cancerous cervical lesions, the same immunobridging assumptions will not be applicable in women over 26 for a number of reasons (see ''Endpoints for evaluation of next-generation vaccines'' section later).…”