Epidemiologic Evaluation of Human Papillomavirus Type Competition and the Potential for Type Replacement Post-Vaccination

Abstract

BackgroundMillions of women have been vaccinated with one of two first-generation human papillomavirus (HPV) vaccines. Both vaccines remain in use and target two oncogenic types (HPVs 16 and 18); however, if these types naturally compete with others that are not targeted, type replacement may occur following reductions in the circulating prevalence of targeted types. To explore the potential for type replacement, we evaluated natural HPV type competition in unvaccinated females.MethodsValid HPV DNA typing information was available from five epidemiological studies conducted in Canada and Brazil (n = 14,685; enrollment across studies took place between1993 and 2010), which used similar consensus-primer PCR assays, capable of detecting up to 40 HPV types. A total of 38,088 cervicovaginal specimens were available for inclusion in our analyses evaluating HPV type-type interactions involving vaccine-targeted types (6, 11, 16, and 18), and infection with each of the other HPV types.ResultsAcross the studies, the average age of participants ranged from 21.0 to 43.7 years. HPV16 was the most common type (prevalence range: 1.0% to 13.8%), and in general HPV types were more likely to be detected as part of a multiple infection than as single infections. In our analyses focusing on each of the vaccine-targeted HPV types separately, many significant positive associations were observed (particularly involving HPV16); however, we did not observe any statistically significant negative associations.ConclusionsOur findings suggest that natural HPV type competition does not exist, and that type replacement is unlikely to occur in vaccinated populations.

Evaluation of HPV type‐replacement in unvaccinated and vaccinated adolescent females—Post‐hoc analysis of a community‐randomized clinical trial (II)

“…The prevalence ratios [PR with 95% confidence interval (CI)] of specific HPV types (HPV6, 11,16,18,31,33,35,39, 45, What's new? Vaccination against high-risk human papilloma virus (HPV) strains is efficacious, but possible resurgence of non-targeted viral strains is a concern.…”

“…7 However, thus far HPV type-replacement has not been observed at the individual level among HPV vaccinated females with low vaccination coverage in the target population. [10][11][12] Implementation of national HPV vaccination programs, however, tends to increase prevalence of some non-vaccine covered HPV types suggesting type-replacement. [10][11][12] Implementation of national HPV vaccination programs, however, tends to increase prevalence of some non-vaccine covered HPV types suggesting type-replacement.…”

“…8,9 A prerequisite of HPV type-replacement, that is, competition between HPV types in unvaccinated populations, has not been commonly found. [10][11][12] Implementation of national HPV vaccination programs, however, tends to increase prevalence of some non-vaccine covered HPV types suggesting type-replacement. 13 HPV epidemiology of vaccination-na€ ıve populations shows that multiple HPV type infections are rare in women with normal cytology (<3%), 14 very common in women with precancer lesions (15-41%) 15 and again rare in women with HPV-related cervical cancer (<12%).…”

Evaluating the potential of vaccine‐induced type replacement for high‐risk human papillomaviruses

“…25 Therefore, several studies evaluating the possibility of HPV type replacement have focussed on finding competitive interactions among HPV types. [46][47][48] Nevertheless, even in the absence of competition mechanisms, the results of this study show that type replacement is viable at the within-host level if the degree of cross-protection induced by the vaccine is not high enough. Type replacement has been observed following vaccination in Durham et al 39 In this study, the authors reported that the prevalence of HPV types phylogenetically related to HPV-16 (types 39, 45, 59, and 68) and HPV-18 (types 39, 45, 59, and 68) increased by 50% and 29% following vaccination, respectively.…”

Human Papillomavirus Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) Cohort Study: Protocol Describing Design, Methods, and Research Goals (Preprint)

“…Pooling data from five pre-vaccination epidemiological studies, including HITCH, and applying a hierarchical Bayesian regression approach that employs shrinkage and adjustment for confounders (i.e., age and lifetime number of sex partners) and other HPV types, we found HPV16 to be the most common type (prevalence range: 1.0% to 13.8%) [32]. HPV types were more likely to be detected as part of a multiple infection than as single infections.…”