Impact and Effectiveness of the Quadrivalent Human Papillomavirus Vaccine: A Systematic Review of 10 Years of Real-world Experience

Abstract

Prophylactic human papillomavirus (HPV) vaccination programs constitute major public health initiatives worldwide. We assessed the global effect of quadrivalent HPV (4vHPV) vaccination on HPV infection and disease. PubMed and Embase were systematically searched for peer-reviewed articles from January 2007 through February 2016 to identify observational studies reporting the impact or effectiveness of 4vHPV vaccination on infection, anogenital warts, and cervical cancer or precancerous lesions. Over the last decade, the impact of HPV vaccination in real-world settings has become increasingly evident, especially among girls vaccinated before HPV exposure in countries with high vaccine uptake. Maximal reductions of approximately 90% for HPV 6/11/16/18 infection, approximately 90% for genital warts, approximately 45% for low-grade cytological cervical abnormalities, and approximately 85% for high-grade histologically proven cervical abnormalities have been reported. The full public health potential of HPV vaccination is not yet realized. HPV-related disease remains a significant source of morbidity and mortality in developing and developed nations, underscoring the need for HPV vaccination programs with high population coverage.

Keywords: CIN; Gardasil/Silgard; HPV vaccination; cervical cancer; genital warts.

Figure 1.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) diagram. Details of literature search and extraction for our systematic review. Abbreviation: HPV, human papillomavirus.

Figure 2.

Impact and effectiveness of quadrivalent human papillomavirus (HPV) vaccination on prevalence of vaccine genotypes. A, Percentage reduction of prevalent HPV 6/11/16/18 infection among vaccinated females compared with prevaccine era or contemporaneous unvaccinated females. B, Percentage reduction of prevalent HPV 6/11/16/18 infection in vaccine era compared with prevaccine era. C, Percentage reduction of prevalent HPV 16/18 infection in vaccine era compared with prevaccine era or contemporaneous unvaccinated females. D, Percentage reduction of prevalent HPV 6/11 infection in vaccine era compared with prevaccine era. In Panel A, “2-doses” refers to an incomplete 3-dose schedule and not a primary 2-dose schedule. More details of the studies shown in the panels of Figure 2 are provided at the end of Supplementary Appendix II.

Figure 3.

Impact and effectiveness of quadrivalent human papillomavirus (4vHPV) vaccination on cervical cytological and histological abnormalities. In Panel B, “2 doses” indicates receipt of an incomplete 3-dose schedule and not a primary 2-dose schedule. More details of the studies shown in the panels of Figure 3 are provided at the end of Supplementary Appendix II. A, Australia: population-based analysis of percentage reduction in cervical abnormalities among vaccinated (at least 1 dose) vs contemporaneous unvaccinated screened females in Victoria [A46, A44]. B, Australia: population-based analysis of percentage reduction in cervical abnormalities among vaccinated vs contemporaneous unvaccinated screened females in Queensland [A45]. C, Canada: percentage reduction in cervical abnormalities in vaccinated/vaccine era vs contemporaneous unvaccinated/prevaccine era in 3 provinces [A47, A20, A58]. D, Denmark: percentage reduction in cervical abnormalities in females vaccinated with 4vHPV vaccine (≥1 dose) vs unvaccinated women by birth cohort [A48]. E, Sweden: percentage reduction in CIN2+ and CIN3+ among females fully vaccinated with 4vHPV vaccine (3 doses) vs unvaccinated/partially vaccinated females, by age at first dose [A50]. F, United States: percentage reduction in HPV 16/18-related cervical abnormalities among females vaccinated with 4vHPV vaccine (at least 1 dose) vs contemporaneous unvaccinated females, by time between first dose and screening test leading to diagnosis; *null: adjusted prevalence ratio 1.02 [A49]. Abbreviations: AIS, adenocarcinoma in situ; ASCUS, atypical squamous cells of undetermined significance; CIN2/3, high-grade cervical intraepithelial neoplasia; LSIL, low-grade squamous intraepithelial lesion.