Objectives Strong and sustained HPV-16 and -18 antibody responses have been observed in previously unexposed women aged 1525 years vaccinated with the AS04-adjuvanted HPV-16/18 L1 virus-like particle vaccine. While awaiting the extended results of ongoing trials, our objective was to predict the long-term persistence of anti-HPV-16/18 antibodies in vaccinees by applying three statistical models using immunogenicity data from vaccinated women with serum samples collected up to 6.4 years after first vaccination. Two different data lock-points (up to 5.5 years and up to 6.4 years) were used to assess the robustness of the models. Methods Three statistical models were applied to estimate the long-term persistence of anti-HPV-16/18 antibodies in 393 women vaccinated with the AS04-adjuvanted HPV-16/18 vaccine. Individual antibody levels for each study participant at each timepoint up to 6.4 years were input to previously published power-law and modified power-law models. The power-law model estimates antibody decay over time. The modified power-law model takes into account both antibody persistence over time and immune memory. A third model, the piece-wise model, fits the data based on three different non-overlapping intervals (between months 7 and 12, months 12 and 21, and over 21 months), corresponding to the observed decay of vaccine-induced antibodies. Results HPV-16 and -18 antibodies peaked at Month 7 and gradually plateaued at months 1824 and remained stable through 6.4 years. Mean antibody levels at the last timepoint were several fold higher than those associated with natural infection. All three models predict that HPV-16 and -18 mean antibody levels will remain well above those associated with natural infection for at least 20 years, when using data from 5.5 as well as 6.4 years' follow-up. Predictions are similar for the modified power-law model and improve with longer follow-up for both the power-law and the piece-wise models. Conclusions Vaccination with the AS04-adjuvanted HPV-16/18 vaccine is predicted to provide long-term persistence for both HPV-16 and -18 antibodies, independent of the statistical model applied. Model predictions are based on conservative mathematical assumptions. Since the input of longer term data of up to 6.4 years showed an improved profile compared with that for data up to 5.5 years, the predictions of antibody persistence based on population means are conservative when predicting that antibody levels will remain well above levels induced by natural infection for 20 years.