Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries.

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.

Safety profile of the 9-valent human papillomavirus vaccine: assessment in prior quadrivalent HPV vaccine recipients and in men 16 to 26 years of age.

A 9-valent HPV (9vHPV) vaccine has been developed to protect against HPV type 6/11/16/18/31/33/45/52/58-related infection and disease. Previous safety analyses from 7 clinical trials conducted in 9vHPV vaccine recipients 9-26 years of age, including comparisons of 9vHPV and quadrivalent HPV (qHPV) vaccines in girls and women 16-26 years of age, showed that the 9vHPV vaccine was generally well tolerated. Additional safety analyses were conducted to include the results of new clinical studies. The safety profile of the 9vHPV vaccine in prior qHPV vaccine recipients (n = 3756 from 1 randomized controlled trial and 2 open-label extension studies) and young men (n = 248 9vHPV and n = 248 qHPV vaccine recipients from 1 randomized controlled trial) was evaluated. Vaccine was administered as a 3-dose regimen (at Day 1 and Months 2 and 6), and adverse events (AEs) were monitored. The most common AEs were injection-site events (91.1% and 79.0% in prior qHPV vaccine recipients and young men, respectively), the majority of which were mild. Discontinuations due to an AE were rare (0.2% and 0.0% among prior qHPV vaccine recipients and young men, respectively). In young men, the AE profile of the 9vHPV vaccine was generally similar to that of the qHPV vaccine. Overall, the 9vHPV vaccine was generally well tolerated in prior qHPV vaccine recipients and in young men, with an AE profile generally consistent with that previously reported with the broader clinical program.

Effect of vessel size on the flow efficiency of the total cavopulmonary connection: in vitro studies.

The total cavopulmonary connection (TCPC) creates a passive system of blood flow into the pulmonary circulation. We hypothesize that the efficiency differences found in models with superior vena cava-inferior vena cava (SVC-IVC) offsets is dependent on vessel size, with flow efficiency improving with larger size vessels. Two sets of in vitro TCPC models (TCPC-3 and TCPC-15) were constructed corresponding to average vessel diameters of 3- and 15-year-old patients. The model with full SVC-IVC offset was the most efficient in TCPC-3 models. There was no significant difference between geometric arrangements in TCPC-15 models; however, the average efficiencies were significantly higher. Among the models representing vessel sizes of the younger age group, the model with the full-diameter SVC-IVC offset was the most efficient. The models representing vessel sizes of the older age group showed marked improvement in efficiencies throughout without obvious differences between various geometric arrangements. This suggests that geometric considerations in TCPC surgical techniques may be of lower than expected significance over the life span of a patient. More important, after balancing the effects of improved flow efficiency with larger vessels against the effects of chronic volume overload, the trend of performing the Fontan surgery on increasingly younger patients may need to be reconsidered after further studies.