A systematic review of immunogenicity, clinical efficacy and safety of human papillomavirus vaccines in people living with the human immunodeficiency virus

The human papillomavirus (HPV) is the most prevalent sexually transmitted infection worldwide. People living with the human immunodeficiency virus (HIV) are at high risk of HPV infection. This systematic review evaluates the immunogenicity, clinical efficacy, and safety of prophylactic HPV vaccines in people living with HIV. We registered the protocol for this review in the International Prospective Register of Systematic Reviews (CRD42018109898) and prepared the review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Five randomized trials with 1042 participants are included in this review. One trial with 120 participants compared the bivalent HPV vaccine to placebo, three trials with 830 participants compared the quadrivalent vaccine to placebo, and another trial with 92 participants compared the quadrivalent to the bivalent vaccine. There was low to moderate certainty evidence suggesting that seroconversion was higher among participants in the vaccine arms compared to the placebo arms for both vaccines. In one study with very low certainty evidence, participants who received the bivalent vaccine had higher anti-HPV-18 geometric mean titers (GMTs) compared to those who received the quadrivalent vaccine, despite little difference in anti-HPV-16 GMTs between the two vaccines. There were no differences in the incident and persistent HPV infections in both groups. None of the studies reported data on the incidence of precancerous lesions, or cancer. There were no reports of serious adverse events following vaccination in any of the trials. None of the included studies assessed the effects of HPV vaccines in adolescents living with HIV. Very limited evidence suggests lower immunogenicity of HPV vaccines in HIV positive compared to HIV-negative people. Finally, the long-term effect of the HPV vaccine in the incidence of cervical precancerous lesions and cervical cancer needs to be monitored. There is an urgent need for more high-quality randomized controlled trials that can address these gaps.