Abstract
This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of two doses (2D) of the HPV-16/18 AS04-adjuvanted vaccine (2D of AS04-HPV-16/18) vs. two or three doses of the 4vHPV vaccine [2D or 3D of 4vHPV] in 1075 healthy girls aged 9–14 years. Girls were randomized (1:1:1) to receive 2D of AS04-HPV-16/18 at months (M) 0, 6 (N = 359), 2D of 4vHPV at M0, 6 (N = 358) or 3D of 4vHPV at M0, 2, 6 (N = 358). 351, 339 and 346 girls, respectively, returned for the concluding visit at M36. Superiority was demonstrated at M7 and M12; comparison of the immune response to both vaccine antigens was made between 2D of AS04-HPV-16/18 and 2D or 3D of 4vHPV at subsequent time points in the according-to-protocol immunogenicity cohort (ATP-I; N = 958 at M36) and the total vaccinated cohort (TVC: N = 1036 at M36). HPV-16/18-specific T-cell- and B-cell-mediated immune responses and safety were also investigated. At M36, anti-HPV-16/18 ELISA responses in the 2D AS04-HPV-16/18 group remained superior to those of the 2D and 3D 4vHPV groups. In the M36 TVC, geometric mean titers were 2.78-fold (HPV-16) and 6.84-fold (HPV-18) higher for 2D of AS04-HPV-16/18 vs. 2D of 4vHPV and 2.3-fold (HPV-16) and 4.14-fold (HPV-18) higher vs. 3D of 4vHPV. Results were confirmed by vaccine pseudovirion-based neutralisation assay. Numbers of circulating CD4+ T cells and B cells appeared similar across groups. Safety was in line with the known safety profiles of both vaccines. In conclusion, superior HPV-16/18 antibody responses were elicited by 2D of the AS04-HPV-16/18 compared with 2D or 3D of the 4vHPV vaccine in girls aged 9–14 years.Clinical Trial Registration: NCT0146235.
Highlights
Today’s estimates suggest that over 500,000 women are diagnosed with cervical cancer every year(y) and more than 260,000 die from the disease [1]
Superiority was demonstrated if lower limit of the 95% confidence intervals (CI) for the ratio of geometric mean antibody titers (GMT) (2D AS04-Human papillomavirus (HPV)-16/18 vaccine divided by 2D or 3D HPV6/11/16/18 vaccine (4vHPV)) was above 1
The recent licensure of 2D schedules of the HPV vaccines for preteens/adolescents is important for global public health, as this is likely to facilitate the introduction of vaccination programs in lower-income countries
Summary
Today’s estimates suggest that over 500,000 women are diagnosed with cervical cancer every year(y) and more than 260,000 die from the disease [1]. HPV vaccination began in 2006/2007 [8,9,10] when the first two HPV vaccines, the HPV-16/18 AS04-adjuvanted (AS04-HPV-16/18) vaccine (Cervarix, GSK) and the HPV6/11/16/18 (4vHPV) vaccine (Gardasil, Merck & Co., Inc.) were licensed for the prevention of cervical cancer and high-grade precursor lesions. Both vaccines contain L1 virus-like particles (VLPs) from the two oncogenic HPV types most prevalent in cervical cancer, i.e. HPV-16 and HPV-18 [1].
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