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extend those findings by presenting results from the blinded analysis conducted at the end of the first four years of follow-up. These results focus on the according to protocol (ATP) efficacy findings submitted to the FDA under BB-IND #7920; separate learn more submissions focus on findings from intent-to-treat and naïve analyses from our trial [12] and [23]. This analysis presents a double-blind randomized controlled trial of an HPV-16/18 vaccine among healthy women 18–25 years old. The study was approved by the Institutional Review Boards in Costa Rica and the US. Detailed methods have been published [11]. In brief, potential participants from a census were invited between June 2004 and December 2005. Eligible women who agreed to participate (N = 7466; estimated to provide >80% power to observe expected differences between arms) were randomized with equal chance to the HPV-16/18 (HPV arm) or Hepatitis A vaccine (control arm), offered in three doses over approximately six months. Blinding to arm assignment was maintained throughout the 48-month follow-up

and until the analytic datafile was frozen. At enrollment, a pelvic exam Selleck Forskolin was performed on sexually experienced women. Exfoliated cells were collected for cytology, HPV DNA, and other tests. At the 6-month visit, women were asked to provide a self-collected cervical specimen for HPV testing. Blood was collected MTMR9 from participants. Each participant was scheduled for annual follow-up examinations (median follow-up time = 53.8 months; inter-quartile range: 50.5–57.0), at which time a pelvic examination was performed on sexually active women, and exfoliated cells and blood were collected. On a pre-defined subset, an additional visit approximately one month following the last vaccine dose was performed where blood

was collected for immunological assessment. Cytology was classified using the Bethesda system. Women with low-grade squamous intraepithelial lesions (LSIL) or HPV positive atypical squamous cells of undetermined significance (ASC-US) were followed semi-annually. The colposcopy referral algorithm used in our trial parallels that used for the PATRICIA trial [6]. Specifically, a repeat LSIL/HPV positive ASC-US, an ASC-US-rule out high-grade SIL (ASC-H), high-grade squamous intraepithelial lesions or more severe disease (HSIL+), or glandular abnormalities prompted colposcopy and treatment as needed [11]. HPV testing using the Hybrid Capture 2 test was performed on enrollment specimens plus specimens from women with an ASC-US cytology during follow-up for clinical management [11]. Broad spectrum PCR-based HPV DNA testing was performed on specimens based on amplification and broad spectrum probe hybridization using the SPF10 HPV DNA enzyme immunoassay system followed by typing using the LiPA25 version 1 line detection system and HPV-16 and -18 type specific testing [11].