Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical intraepithelial neoplasia and cervical infection in young Japanese women

Abstract

In this open, extended follow-up study (NCT00929526, Clinicaltrials.gov), we evaluated the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine efficacy, immunogenicity and safety up to 4 years after first vaccination in Japanese women aged 20–25 years. In the initial randomized, double-blind study (NCT00316693), 1040 women received the study vaccine or hepatitis A control vaccine; 752 women were included in the follow-up study. In women from the according-to-protocol efficacy cohort (ATP-E), who were initially seronegative for the HPV type analyzed, no cervical intraepithelial neoplasia (CIN) grade 1 or greater (CIN1+) cases associated with HPV-16/18 were reported in the HPV group, while in the control group, 5 cases were identified in extended follow-up analyses (vaccine efficacy [VE] 100% [95% CI: −3.7–100]) and 8 cases in combined initial and follow-up studies analyses (VE 100% [42.2–100]). In the ATP-E, VE against CIN1+ and CIN2+ associated with high-risk HPV types reached 66.4% (21.6–87.1) and 83.0% (22.1–98.2) in extended follow-up analyses, and 63.4% (28.8–82.3) and 77.3% (30.4–94.4) in analyses of combined studies, respectively. During the 4-year period, protection against CIN1+ and CIN2+, irrespective of the HPV type, was 56.7% (32.8–72.6) and 54.9% (20.5–75.3) in women receiving ≥1 vaccine dose, regardless of baseline serostatus (total vaccinated cohort [TVC]) and 61.0% (11.8–84.2) and 73.9% (1.1–95.3) in women naïve to HPV infection at baseline (TVC-naïve), respectively. The high VE observed in Japanese women, accompanied by a sustained immune response and a clinically acceptable safety profile, support findings of large, international trials.

Efficacy of the HPV-16/18 vaccine: Final according to protocol results from the blinded phase of the randomized Costa Rica HPV-16/18 vaccine trial

“…Our results confirm the high efficacy of VLP-based vaccines against incident CIN2+ associated with HPV-16/18 [4-10]. It is reassuring that high efficacy against infections and lesions associated with the HPV types in the vaccine formulation has now been reported for VLP-based vaccines from multiple trials conducted in different populations, despite differences in study methodology [4-10, 26, 27] (Table 4). Furthermore, our report is consistent with previous results suggesting that vaccination with the HPV-16/18 vaccine might confer partial protection against some oncogenic HPV types not included in the vaccine formulation [28].…”

Human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for the prevention of cervical cancer and HPV-related diseases

“…An event-driven interim analysis and an end-of-study analysis at 24 months were conducted for the initial study [38,39] and a 4year analysis for the extension study. [40] The HPV-039 trial (NCT00779766) is an ongoing trial conducted in China in healthy women aged 18-25 years (N = 6051), and the event-driven final analysis per protocol has been reported. [41] The HPV-015 Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy (VIVIANE) trial (NCT00294047) was conducted in 12 countries in Europe, Australia, Southeast Asia, and North and South America (N = 5752) and enrolled women aged more than 25 years irrespective of past sexual behavior, cytology, HPV serostatus, or DNA status.…”

“…[41] The HPV-015 Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy (VIVIANE) trial (NCT00294047) was conducted in 12 countries in Europe, Australia, Southeast Asia, and North and South America (N = 5752) and enrolled women aged more than 25 years irrespective of past sexual behavior, cytology, HPV serostatus, or DNA status. It included a subset of up to 15% of women with a history of HPV infection/disease in each age stratum (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45), and >45 years). An interim analysis 4 years after the first vaccination has been reported.…”

“…[42] Vaccine efficacy against CIN1+, CIN2+, and CIN3+ irrespective of HPV DNA in the 4year analysis of the Japanese trial (HPV-032/063) was 56 1-95.3), and 100% (−417.0-100), respectively, in the TVC-naïve. [40] Analysis of vaccine efficacy against CIN2+ irrespective of HPV was performed in the ATP cohort for the CVT. [32] Two definitions of the endpoint (a priori and exploratory), different from that in the aforementioned trials, were used, as described by Hildesheim and colleagues.…”

Naprotecnología: ciencia y persona en la infección por el virus del papiloma humano (VPH) en mujeres y preadolescencentes

“…Ambas vacunas contra el VPH (4vHPV y 2vHPV) han tenido un impacto significativo y se ha demostrado la eficacia en el VPH que se propaga por vía sexual, al proteger contra las complicaciones como la displasia cervical (68)(69)(70)(71)(72)(73)(74). Tres dosis de cada vacuna contra el VPH siguen siendo recomendables, pero hay cierta evidencia de que dos dosis de HPV2 pueden ser efectivas (75).…”