Adolescents are the primary population for HPV vaccination, and more evidence is needed on the efficacy and safety of HPV vaccination in adult women. Therefore, the FDA only recommends HPV vaccination for women under 26 years of age. This study is an intermediate analysis of the ongoing study VIVIANE to assess the immunogenicity of the AS04-prepared HPV 16/18 vaccine in adult women. In this phase III, multi-country, double-blind, randomized controlled study, healthy women aged 25 years and older were randomized in a 1:1 ratio to receive HPV 16/18 vaccination or control. Recruitment was adjusted for stratification by age, with the 26-35, 36-45, and >46 age groups accounting for 45%, 45%, and 10%, respectively. At least 15% of women in each age group had a history of prior HPV infection or related disease. Study endpoints were vaccine efficacy for 6-month persistent infection or HPV 16/18-associated lesions of CIN 1 or higher. The mean follow-up was 40.3 months. A total of 5752 women entered the study (2881 in the vaccine arm and 2871 in the control arm), and 4505 entered the final effectiveness analysis (2264 in the vaccine arm and 2241 in the control arm). Efficacy against HPV 16/18-associated 6-month persistent infection, or against CIN 1+, was highly significant in the overall age group (81.1%, 97.7% CI 52.1-94.0%), 83.5% and 77.2% in the 26-35 and 36-45 years age groups, respectively, with no relevant cases found in the >45 years age group. Vaccine protection against atypical squamous cells of undefined significance (ASCUS) or more severe lesions associated with HPV 16/18 was also highly significant. The authors also noted significant cross-protection of the vaccine against HPV 31, HPV 45-associated persistent infection at 6 months. The incidence of serious adverse events in the vaccine and control groups was 10% and 9%, respectively, with 5 and 8 cases in the two groups, respectively, thought to be related to vaccination practices. Accordingly, the authors concluded that for women over 25 years of age, HPV 16/18 vaccine is effective in preventing infection and cervical abnormalities with cross-protective effects of HPV 31 and HPV 45.