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Randomized Controlled Trial
. 2015 Oct 14;108(1):djv302.
doi: 10.1093/jnci/djv302. Print 2016 Jan.

Multisite HPV16/18 Vaccine Efficacy Against Cervical, Anal, and Oral HPV Infection

Daniel C Beachler  1 , Aimée R Kreimer  2 , Mark Schiffman  2 , Rolando Herrero  2 , Sholom Wacholder  2 , Ana Cecilia Rodriguez  2 , Douglas R Lowy  2 , Carolina Porras  2 , John T Schiller  2 , Wim Quint  2 , Silvia Jimenez  2 , Mahboobeh Safaeian  2 , Linda Struijk  2 , John Schussler  2 , Allan Hildesheim  2 , Paula Gonzalez  2 ; Costa Rica HPV Vaccine Trial (CVT) Group
Collaborators, Affiliations
Randomized Controlled Trial

Multisite HPV16/18 Vaccine Efficacy Against Cervical, Anal, and Oral HPV Infection

Daniel C Beachler et al. J Natl Cancer Inst. .

Abstract

Background: Previous Costa Rica Vaccine Trial (CVT) reports separately demonstrated vaccine efficacy against HPV16 and HPV18 (HPV16/18) infections at the cervical, anal, and oral regions; however, the combined overall multisite efficacy (protection at all three sites) and vaccine efficacy among women infected with HPV16 or HPV18 prior to vaccination are less known.

Methods: Women age 18 to 25 years from the CVT were randomly assigned to the HPV16/18 vaccine (Cervarix) or a hepatitis A vaccine. Cervical, oral, and anal specimens were collected at the four-year follow-up visit from 4186 women. Multisite and single-site vaccine efficacies (VEs) and 95% confidence intervals (CIs) were computed for one-time detection of point prevalent HPV16/18 in the cervical, anal, and oral regions four years after vaccination. All statistical tests were two-sided.

Results: The multisite woman-level vaccine efficacy was highest among "naïve" women (HPV16/18 seronegative and cervical HPV high-risk DNA negative at vaccination) (vaccine efficacy = 83.5%, 95% CI = 72.1% to 90.8%). Multisite woman-level vaccine efficacy was also demonstrated among women with evidence of a pre-enrollment HPV16 or HPV18 infection (seropositive for HPV16 and/or HPV18 but cervical HPV16/18 DNA negative at vaccination) (vaccine efficacy = 57.8%, 95% CI = 34.4% to 73.4%), but not in those with cervical HPV16 and/or HPV18 DNA at vaccination (anal/oral HPV16/18 VE = 25.3%, 95% CI = -40.4% to 61.1%). Concordant HPV16/18 infections at two or three sites were also less common in HPV16/18-infected women in the HPV vaccine vs control arm (7.4% vs 30.4%, P < .001).

Conclusions: This study found high multisite vaccine efficacy among "naïve" women and also suggests the vaccine may provide protection against HPV16/18 infections at one or more anatomic sites among some women infected with these types prior to HPV16/18 vaccination.

Trial registration: ClinicalTrials.gov NCT00128661.

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Figures

Figure 1.
Figure 1.
Consort diagram for this Costa Rica Vaccine trial–based study. Asterisks indicate no baseline anal or oral sampling, so a true “According-to-Protocol” analysis could not be included. HPV = human papillomavirus; LEEP = loop electrosurgical excision procedure.
Figure 2.
Figure 2.
Type-specific concordance of human papillomavirus (HPV) 16/18 infections at the four-year follow-up visit among 2092 women in the control arm and 2094 women in the HPV vaccine arm. The kappa for anal/cervical HPV16/18 agreement was 0.44 (95% confidence interval [CI] = 0.37 to 0.51) for the control arm and 0.13 (95% CI = 0.03 to 0.23) for the vaccine arm. The percentages on the figure indicate the amount of HPV16/18 infections that were concordant at another anatomic site. Seventy-five of the 79 concordant infections were anal/cervical infections. One individual was infected at all three sites. HPV = human papillomavirus.
See this image and copyright information in PMC

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References

    1. Kjaer SK, Sigurdsson K, Iversen OE, et al. A pooled analysis of continued prophylactic efficacy of quadrivalent human papillomavirus (Types 6/11/16/18) vaccine against high-grade cervical and external genital lesions. Cancer Prev Res (Phila). 2009;2 (10):868–878. - PubMed
    1. Lehtinen M, Paavonen J, Wheeler CM, et al. Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012;13 (1):89–99. - PubMed
    1. Herrero R, Wacholder S, Rodriguez AC, et al. Prevention of persistent human papillomavirus infection by an HPV16/18 vaccine: a community-based randomized clinical trial in Guanacaste, Costa Rica. Cancer Discov. 2011;1 (5):408–419. - PMC - PubMed
    1. Hildesheim A, Wacholder S, Catteau G, et al. Efficacy of the HPV-16/18 vaccine: final according to protocol results from the blinded phase of the randomized Costa Rica HPV-16/18 vaccine trial. Vaccine. 2014;32 (39):5087–5097. - PMC - PubMed
    1. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29 (32):4294–4301. - PMC - PubMed

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