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. 2017 Jul;145(10):1962-1982.
doi: 10.1017/S0950268817000747. Epub 2017 Apr 27.

Human Papillomavirus 9-valent Vaccine for Cancer Prevention: A Systematic Review of the Available Evidence

Free PMC article

Human Papillomavirus 9-valent Vaccine for Cancer Prevention: A Systematic Review of the Available Evidence

C Signorelli et al. Epidemiol Infect. .
Free PMC article


In 2014, the Food and Drug Administration approved a new human papillomavirus 9-valent vaccine (9vHPV), targeting nine HPV types: HPV types 6, 11, 16, and 18, which are also targeted by the quadrivalent HPV vaccine (qHPV), plus five additional high cancer risk HPV types (HPV types 31, 33, 45, 52, and 58). The aim of the current study was to systematically retrieve, qualitatively and quantitatively pool, as well as critically appraise all available evidence on 9vHPV from randomized controlled trials (RCTs). We conducted a systematic review of the literature on 9vHPV efficacy, immunogenicity and safety, as well as a systematic search of registered, completed, and ongoing RCTs. We retrieved and screened 227 records for eligibility. A total of 10 publications reported on RCTs' results on 9vHPV and were included in the review. Sixteen RCTs on 9vHPV have been registered on RCT registries. There is evidence that 9vHPV generated a response to HPV types 6, 11, 16 and 18 that was non-inferior to qHPV. Vaccine efficacy against five additional HPV type-related diseases was directly assessed on females aged 16-26 years (risk reduction against high-grade cervical, vulvar or vaginal disease = 96·7%, 95% CI 80·9%-99·8%). Bridging efficacy was demonstrated for males and females aged 9-15 years and males aged 16-26 years (the lower bound of the 95% CIs of both the geometric mean titer ratio and difference in seroconversion rates meeting the criteria for non-inferiority for all HPV types). Overall, 9vHPV has been proved to be safe and well tolerated. Other RCTs addressed: 9vHPV co-administration with other vaccines, 9vHPV administration in subjects that previously received qHPV and 9vHPV efficacy in regimens containing fewer than three doses. The inclusion of additional HPV types in 9vHPV offers great potential to expand protection against HPV infection. However, the impact of 9vHPV on reducing the global burden of HPV-related disease will greatly depend on vaccine uptake, coverage, availability, and affordability.

Keywords: human papillomavirus 9-valent vaccine; Cancer prevention; HPV; systematic review.


Fig. 1.
Fig. 1.
PRISMA flowchart of included published papers.
Fig. 2.
Fig. 2.
PRISMA flowchart of included registered trials (update August 25, 2016).

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    1. World Health Organization. International Agency for Research on Cancer. Globocan, 2012. ( Accessed 23 August 2016.
    1. de Martel C, et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncology 2012; 13(6): 607–615. - PubMed
    1. The World Health Organization. Human papillomavirus (HPV) and cervical cancer. Fact sheet Updated June 2016 ( Accessed 4 August 2016.
    1. Burd EM. Human papillomavirus and cervical cancer. Clinical Microbiology Reviews 2003; 16(1): 1–17. - PMC - PubMed
    1. The World Health Organization. International Agency for Research on Cancer (IARC). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 90. Human Papillomaviruses; Lyon, France, 2007.

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