Bivalent HPV vaccine has cross-protective effect, but could wane over time

The bivalent vaccine for human papillomavirus (HPV) types 16 and 18 appears to be more efficacious against outcomes associated with nonvaccine types 31, 33, and 45 than its quadrivalent counterpart, show results of a systematic review and meta-analysis.

However, the efficacy of the bivalent vaccine against persistent infection and cervical intraepithelial neoplasia (CIN)2+ disease associated with HPV 31, 33, and 45 appeared to decrease over time, suggesting a "waning of cross-protection," say the researchers.

The team notes that the quadrivalent HPV vaccine, designed to protect against HPV 6, 11, 16, and 18 also showed significant efficacy against 6-month persistent HPV 31 infection.

"Our results are of particular importance for clinicians, epidemiologists, modellers, and policy makers who compare vaccines and make recommendations on which HPV vaccine to use," remark Marc Brisson (Centre Hospitalier Affilié Universitaire de Québec, Canada) and colleagues in Lancet Infectious Diseases.

"HPV types 31, 33, and 45 are present in a notable proportion of cervical cancers worldwide... Cross-protection afforded by the HPV vaccines is a key factor of interest," they say.

The findings emerge from analysis of five published trials (three for the bivalent vaccine Cervarix [GlaxoSmithKline Biologicals, Rixensart, Belgium], and two for the quadrivalent Gardasil [Merck, Whitehouse Station, New Jersey, USA]) that followed women who were initially HPV negative for 14 HPV types.

In the bivalent and quadrivalent studies with the most similar follow up lengths (PATRICIA and FUTURE I/II, 3.6 years) the researchers report higher vaccine efficacy against 6-month persistent HPV 31, 33, and 45 with the bivalent vaccine, at 77.1% versus 46.2%, 43.1% versus 28.7%, and 79.0% versus 7.8%, respectively. The difference in efficacy against HPV 33 was nonsignificant however.

Overall, estimates of efficacy declined between the study with the shortest follow up - a mean of 3.6 years - to that with the longest - 9.0 years.

The authors observed significant efficacy of the quadrivalent vaccine against CIN2+ associated with HPV 31 when lesions co-infected with HPV 16 or 18 were included, and these estimations only declined moderately when the latter types were excluded from analysis.

"This finding suggests that, although part of the reported efficacy against non-vaccine types might be attributable to HPV 16 or 18, a cross-protective effect remains for some non-vaccine type HPVs," the research team concludes.

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