Evaluation of safety and immunogenicity of a quadrivalent human papillomavirus vaccine in healthy females between 9 and 26 years of age in Sub-Saharan Africa

Abstract

Due to sporadic and not easily accessible cervical cancer screening, human papillomavirus (HPV)-related cervical cancer is a leading cause of cancer death in Sub-Saharan African women. This study was designed to assess the safety and immunogenicity of a quadrivalent human papillomavirus (qHPV) vaccine in sub-Saharan African women. This seven month, double-blind study enrolled 250 healthy, human immunodeficiency virus (HIV)-uninfected females ages 9-26 residing in Ghana, Kenya, and Senegal. Thirty females ages 13-15 and 120 females ages 16-26 received qHPV vaccine. In addition, 100 females ages 9-12 y were randomized in a 4:1 ratio to receive either qHPV vaccine (n = 80) or placebo (n = 20 ). The primary immunogenicity hypothesis was that an acceptable percentage of subjects who received the qHPV vaccine seroconvert to HPV6/11/16/18 at 4 weeks post-dose 3, defined as the lower bound of the corresponding 95% confidence interval (CI) exceeding 90%. The primary safety objective was to demonstrate that qHPV vaccine was generally well tolerated when administered in a 3-dose regimen. The pre-specified statistical criterion for the primary immunogenicity hypothesis was met: the lower bound of the 95% exact binomial CI on the seroconversion rate was at least 98% for each vaccine HPV type and all subjects seroconverted by 4 weeks post-dose 3. Across vaccination groups, the most common adverse events (AE) were at the injection site, including pain, swelling, and erythema. No subject discontinued study medication due to an AE and no serious AEs were reported. There were no deaths. This study demonstrated that qHPV vaccination of sub-Saharan African women was highly immunogenic and generally well tolerated.

Keywords: AE, adverse event; CDC, Centers for Disease Control and Prevention; CI, confidence interval; FDA, Food and Drug Administration; GMT, geometric mean titers; HIV, human immunodeficiency virus; HPV, human papillomavirus; ICC, invasive cervical cancer; LSIL, low-grade squamous intraepithelial lesions; mMU/mL; PCR, polymerase chain reaction; Pap, papanicolaou; US, United States; VRC, vaccination report card; cLIA, competitive Luminex immunoassay; immunogenicity; milli Merck Units/mL; qHPV, quadrivalent human papillomavirus; quadrivalent HPV vaccine; safety; sub-Saharan Africa.