Prevention of Persistent Human Papillomavirus Infection by an HPV16/18 Vaccine: A Community-Based Randomized Clinical Trial in Guanacaste, Costa Rica

Proyecto Epidemiológico Guanacaste, Fundación Instituto Costarricense de Investigación y Enseñanza en Nutrición y Salud, San José, Costa Rica.
Cancer Discovery (Impact Factor: 19.45). 10/2011; 1(5):408-19. DOI: 10.1158/2159-8290.CD-11-0131
Source: PubMed

ABSTRACT Target groups for human papillomavirus (HPV) vaccination are controversial. We evaluated vaccine efficacy (VE) against 1-year persistent infection, stratified by age and sexual behavior, among young women in Costa Rica. We randomized 7,466 healthy women 18 to 25 years of age to HPV16/18 or hepatitis A vaccine (follow-up, 50.4 months). According-to-protocol (ATP) cohorts included compliant HPV-negative women; intention-to-treat (ITT) included all randomized women. ATP VE was 90.9% (95% CI, 82.0-95.9) against HPV16/18 infections, 44.5% against HPV31/33/45 (95% CI, 17.5-63.1), and 12.4% (95% CI, -3.2 to 25.6) against any oncogenic infection. Overall ITT VE against HPV16/18 infections was 49.0%, but ATP and ITT VE almost reached 100% in year 4 of follow-up. ATP efficacy against HPV16/18 was similar by age, but ITT VE was greatest among youngest women (68.9% among those 18-19 years of age; 21.8% among those 24-25 years of age) and 79.8% among virgins. Among previously unexposed women, vaccination is highly efficacious against HPV16/18 and partially against HPV31/33/45. Vaccination is most effective in women and girls before they initiate sexual activity, with programmatic and individual decision implications.

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Available from: Ana Cecilia Rodriguez, Jun 10, 2014
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    • "These challenges are magnified in developing countries with fewer human resources and less Fig. 3. HPV16 and HPV18 specific antibody geometric mean titers by number of doses received among girls aged 10–12 years in Uganda (≥24 months after last vaccine dose) and women aged 18–25 years in Costa Rica (≥24 months after first dose). Dashed lines are levels from naturally infected women in Costa Rica HPV16/18 Vaccine trial that were shown to confer immune protection from future infections (60 EU/mL for HPV16 and 28 EU/mL for HPV18) [34] [35]. Table 3 Studies reporting long-term immunogenicity a of the HPV16/18 AS04-adjuvanted vaccine among adolescent and adult females. "
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    ABSTRACT: Background: Investigations of vaccine efficacy and immunogenicity for adult females receiving fewer than three doses of human papillomavirus (HPV) vaccine have suggested protection against infection and precancerous lesions. We investigated the immunogenicity of bivalent HPV vaccines among adolescent girls from Uganda who received one, two, or three vaccine doses. Methods: Young girls vaccinated through a government program in Uganda were invited to participate. HPV16- and HPV18-specific antibodies were measured at >= 24 months after the last vaccine dose using an enzyme linked immunoassay in girls who received one (n = 36), two (n = 145), or three (n = 195) doses. Results: Nearly all subjects (99%) were HPV16 and HPV18 seropositive at the time of blood-draw. Geometric mean antibody levels (GMTs) were: HPV16(1-dose) = 230 EU/mL, HPV16(2-dose) = 808 EU/mL, and HPV16(3-dose) = 1607 EU/mL; HPV18(1-dose) = 87 EU/mL, HPV18(2-dose) = 270 EU/mL, and HPV18(3-dose) = 296 EU/mL. The GMT ratio for 2:3 doses was 0.50 (HPV16) and 0.68 (HPV18) and did not meet the non-inferiority criteria (i.e., lower bound of 97.5% confidence interval of the GMT ratio greater than 0.50). The GMT ratio for 1:3 doses for HPV16 and HPV18 was inferior, but absolute GMTs for one dose were higher than adult women who received one dose (HPV16 = 124 EU/mL, HPV18 = 69 EU/mL) where efficacy has been demonstrated. Conclusions: Even though immunogenicity with less than three doses did not meet a priori non-inferiority thresholds, antibody levels measured >= 24 months after last dose were similar to those of adult women who have been followed for more than eight years for efficacy. (C) 2014 Published by Elsevier Ltd.
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    • "We now extend those findings by presenting results from the blinded analysis conducted at the end of the first four years of follow-up. These results focus on the according to protocol (ATP) efficacy findings submitted to the FDA under BB-IND #7920; separate submissions focus on findings from intent-to-treat and naïve analyses from our trial [12] [23]. "
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    ABSTRACT: Three-dose regimens for human papillomavirus (HPV) vaccines are expensive and difficult to complete, especially in settings where the need for cervical cancer prevention is greatest. We evaluated the vaccine efficacy of fewer than three doses of the HPV16/18 vaccine Cervarix in our Costa Rica Vaccine Trial. Women were randomly assigned to receive three doses of the HPV16/18 vaccine or to a control vaccine and were followed for incident HPV16 or HPV18 infection that persisted in visits that were 10 or more months apart (median follow-up 4.2 years). After excluding women who had no follow-up or who were HPV16 and HPV18 DNA positive at enrollment, 5967 women received three vaccine doses (2957 HPV vaccine vs 3010 control vaccine), 802 received two doses (422 HPV vs. 380 control), and 384 received one dose (196 HPV vs. 188 control). Reasons for receiving fewer doses and other pre- and post-randomization characteristics were balanced within each dosage group between women receiving the HPV and control vaccines. Incident HPV16 or HPV18 infections that persisted for 1 year were unrelated to dosage of the control vaccine. Vaccine efficacy was 80.9% for three doses of the HPV vaccine (95% confidence interval [CI] = 71.1% to 87.7%; 25 and 133 events in the HPV and control arms, respectively), 84.1% for two doses (95% CI = 50.2% to 96.3%; 3 and 17 events), and 100% for one dose (95% CI = 66.5% to 100%; 0 and 10 events). Four years after vaccination of women who appeared to be uninfected, this nonrandomized analysis suggests that two doses of the HPV16/18 vaccine, and maybe even one dose, are as protective as three doses.
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