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Randomized Controlled Trial
. 2017 Jan 28;109(7):djw300.
doi: 10.1093/jnci/djw300. Print 2017 Jan.

Evaluation of Type Replacement Following HPV16/18 Vaccination: Pooled Analysis of Two Randomized Trials

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Free PMC article
Randomized Controlled Trial

Evaluation of Type Replacement Following HPV16/18 Vaccination: Pooled Analysis of Two Randomized Trials

Joseph E Tota et al. J Natl Cancer Inst. .
Free PMC article

Abstract

Background: Current HPV vaccines do not protect against all oncogenic HPV types. Following vaccination, type replacement may occur, especially if different HPV types competitively interact during natural infection. Because of their common route of transmission, it is difficult to assess type interactions in observational studies. Our aim was to evaluate type replacement in the setting of HPV vaccine randomized controlled trials (RCTs).

Methods: Data were pooled from the Costa Rica Vaccine Trial (CVT; NCT00128661) and PATRICIA trial (NCT001226810)-two large-scale, double-blind RCTs of the HPV-16/18 AS04-adjuvanted vaccine-to compare cumulative incidence of nonprotected HPV infections across trial arms after four years. Negative rate difference estimates (rate in control minus vaccine arm) were interpreted as evidence of replacement if the associated 95% confidence interval excluded zero. All statistical tests were two-sided.

Results: After applying relevant exclusion criteria, 21 596 women were included in our analysis (HPV arm = 10 750; control arm = 10 846). Incidence rates (per 1000 infection-years) were lower in the HPV arm than in the control arm for grouped nonprotected oncogenic types (rate difference = 1.6, 95% confidence interval [CI] = 0.9 to 2.3) and oncogenic/nononcogenic types (rate difference = 0.2, 95% CI = -0.3 to 0.7). Focusing on individual HPV types separately, no deleterious effect was observed. In contrast, a statistically significant protective effect (positive rate difference and 95% CI excluded zero) was observed against oncogenic HPV types 35, 52, 58, and 68/73, as well as nononcogenic types 6 and 70.

Conclusion: HPV type replacement does not occur among vaccinated individuals within four years and is unlikely to occur in vaccinated populations.

Figures

Figure 1.
Figure 1.
Trial profile for Costa Rica Vaccine Trial (CVT) and PATRICIA trial pooled analysis. *Women may have contributed no time at risk because of prevalent infection with a vaccine-protected type that did not clear before their final study visit (excluded from analysis). †Oncogenic infections of interest include HPV types 35, 39, 51, 52, 56, 58, 59, and 68/73. ‡Nononcogenic HPV types of interest include HPV types 6, 11, 34, 40, 42, 43, 44, 53, 54, 66, 70, and 74. HPV = human papillomavirus.
Figure 2.
Figure 2.
Rate difference (rate in the control minus the vaccine arm) and efficacy of the HPV-16/18 vaccine against individual oncogenic and nononcogenic HPV infections (excluding types that the vaccine has shown consistent and strong evidence of efficacy against: HPVs 16, 18, 31, 33, and 45). The error bars represent the 95% confidence intervals. HPV = human papillomavirus.

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