Inge Verdenius and colleagues1
suggest that cross-protection with the human papillomavirus (HPV) vaccine Cervarix might prevent genotype replacement. Some points deserve further discussion. To our knowledge, only one study2
has reported an increase in prevalence of non-vaccine HPV types after vaccination. However, that such increase is induced by vaccination, and thus, that genotype replacement is taking place, is not certain. Nevertheless, we agree that genotype replacement could be happening, because that increase was significant for vaccinated, but not unvaccinated, participants. Yet, the conclusion that genotype replacement is happening in patients vaccinated with Gardasil on the basis of findings from only one study seems premature.
Notably, Tabrizi and colleagues'2
findings for Gardasil were not in line with those of Kahn and colleagues,3
because they reported a slight (non-significant) reduction in the prevalence of non-vaccine HPV types in the postvaccination era in Australia (table
). Awaited surveillance data for the two available vaccines from different settings with varying vaccination coverage should show whether genotype replacement is indeed at work.
Surveillance studies comparing prevalence of HPV types pre-vaccination and post-vaccination
Verdenius and colleagues' hypothesis1
followed Malagón and coworkers4
meta-analysis of vaccine-induced cross-protection. However, results of that meta-analysis should be interpreted with caution, because Malagón and coworkers reported significant differences between the two vaccines for persistent infections with HPV types 31 and 45, but not for type 33, for which CIs largely overlapped. Moreover, the two vaccines did not differ for either types 58 and 52, which are both related to type 16 and are largely present in cervical lesions in Asia.5
The investigators noted that efficacy of Cervarix decreased during follow-up, suggesting waning cross-protection. Overall, if vaccine cross-protection lasts only less than a decade, its beneficial effects, potentially including prevention of genotype replacement, could merely be transitory.
Should Verdenius and colleagues' hypothesis prove true, that Cervarix cross-protection could counterbalance genotype replacement, then two events could happen: HPV types, for which some degree of Cervarix cross-protection has been reported,4
would correspond to those increasing in the population vaccinated with Gardasil;2
or those types would differ, but would somehow interact indirectly through other HPV types. Because Kahn and colleagues2
did not report prevalence data by genotype, whether such HPV-genotype matching happens is unknown.
Available data are insufficient to infer that vaccine cross-protection might prevent genotype replacement. To assess vaccination effects on prevalence of non-vaccine HPV types, surveillance studies should provide data by genotype. Such information is essential for disease prevention in the near future because oncogenic potentials of HPV types differ, and changes in incidence of HPV-related disease are preceded by changes in prevalence of HPV-type infection.
We declare that we have no conflicts of interest.