Impact of 2-, 4- and 9-valent HPV vaccines on morbidity and mortality from cervical cancer.

Cervical cancer causes significant morbidity and mortality worldwide. Most cervical cancers are associated with oncogenic human papillomavirus (HPV), and vaccination with any of 3 available HPV vaccines is anticipated to greatly reduce the burden of cervical cancer. This review provides an overview of the burden of HPV, the efficacy and clinical effectiveness of the bivalent (HPV 16, 18), quadrivalent (HPV 6, 11, 16, 18) and 9vHPV (HPV 6, 11, 16, 1831, 33, 45, 52, 58) vaccines in order to assess the anticipated impact on cervical cancer. All three vaccines show high efficacy in prevention of vaccine-specific HPV-type infection and associated high-grade cervical dysplasia in HPV-naïve women. Early clinical effectiveness data for the bivalent and quadrivalent vaccine demonstrate reduced rates of HPV 16 and 18 prevalence in vaccinated cohorts; data evaluating cervical dysplasia and cervical procedures as outcomes will shed further light on the clinical effectiveness of both vaccines. The bivalent vaccine has demonstrated cross-protection to non-vaccine HPV types, including the types in the 9vHPV vaccine. No clinical effectiveness data is yet available for the 9vHPV vaccine.  While HPV vaccination has great promise to reduce cervical cancer morbidity and mortality, estimated benefits are largely theoretical at present. Large population-based clinical effectiveness studies will provide long-term immunogenicity and effectiveness, as well as assessment of cervical cancer as an endpoint, particularly as young vaccinated women enter the appropriate age range to initiate screening for cervical cancer. Strengthening screening and treatment programs will likely have the greatest impact in the short-term on cervical cancer morbidity and mortality.