Real-World Impact (RWI) data provide evidence of a vaccine’s ability to reduce infection and disease in a general population and help to inform policy and implementation decisions. Clinical trial data provided strong evidence regarding the efficacy of the quadrivalent and bivalent human papillomavirus (HPV) vaccines (4vHPV and 2vHPV vaccines). Some degree of cross-protection efficacy against non-vaccine HPV types was reported for both vaccines, although reported data showed a lack of consistent protection and short duration of that protection. In this review, we discuss cross-protection results in light of the RWI evidence.
Population-based studies and meta-analysis were reviewed to evaluate the impact of vaccination programs with high coverage and high series-completion on HPV prevalence, high-grade disease associated to non-vaccine types as well as high-grade lesions irrespective of HPV type.
Evidence from the meta-analysis with more than 140 million person-years of follow-up data supports the role of HPV vaccination in decreasing Genital Warts Incidence and HPV 16/18 prevalence which fell by 72% (RR: 0.28 (0.14–0.56)) in the post-vaccination period, compared to the pre-vaccination period, in women 13 to 19 years of age receiving 4vHPV.
Partial though significant reductions in HPV types 31 and 45 were reported after 4vHPV in Australia (P=0.0029 and P=0.0043 for HPV 31 and 45, respectively); similar results were reported for 2vHPV showed statistically significant reductions in the prevalence of HPV 31, 33 or 45 in women fully vaccinated in Scotland (P=0.0002; P=0.002; P=0.001, respectively) and non-significant results in the UK.
Reductions of CIN1 by 29%, CIN2 by 50%, and CIN3 by 55% in 20-21 year-old women vaccinated with 2vHPV in Scotland and up to 80% reduction in CIN 2/3 and CIN 3 in women aged before 20 years in Denmark with 4vHPV showed the overall effect on high-grade disease irrespective of HPV type.
RWI data support high efficacy against VLP-based vaccine HPV types and partial cross-protection effect against few non-vaccine HPV types for both vaccines. Overall reduction in CIN2/3 and CIN3 due to HPV types included as well as those not included in the vaccines suggest that even in short-term RWI data, the effect of cross-protection is modest. Furthermore, the high efficacy results attributed to cross-protection and referred to as Population Impact in a single clinical trial are not observed in RWI studies. The nine-valent HPV vaccine directly targets the most common oncogenic HPV types, making short-duration cross-protection even less relevant for public health programs.