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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    • "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: HPV16₁-dose=230 EU/mL, HPV16₂-dose=808 EU/mL, and HPV16₃-dose=1607 EU/mL; HPV18₁-dose=87 EU/mL, HPV18₂-dose=270 EU/mL, and HPV18₃-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.
    Vaccine 09/2014; 32(47). DOI:10.1016/j.vaccine.2014.08.071 · 3.62 Impact Factor
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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: A community-based randomized trial was conducted in Costa Rica to evaluate the HPV-16/18 AS04-adjuvanted vaccine (NCT00128661). The primary objective was to evaluate efficacy of the vaccine to prevent cervical intraepithelial neoplasia 2 or more severe disease (CIN2+) associated with incident HPV-16/18 cervical infections. Secondary objectives were to evaluate efficacy against CIN2+ associated with incident cervical infection by any oncogenic HPVs and to evaluate duration of protection against incident cervical infection with HPV-16/18. Vaccine safety and immunogenicity over the 4-year follow-up were also evaluated.
    Vaccine 09/2014; 32(39). DOI:10.1016/j.vaccine.2014.06.038 · 3.62 Impact Factor
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    • "The lack of significant differences in HPV prevalence in the higher age groups in our study is likely due to the fact that most vaccinated women in these age groups were vaccinated long after first sexual intercourse. This might have negatively impacted on vaccine effectiveness [30]. These findings support the recommendation to vaccinate early in adolescence and before sexual debut. "
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    ABSTRACT: Estimates of Human Papillomavirus (HPV) prevalence in a population prior to and after HPV vaccine introduction are essential to evaluate the short-term impact of vaccination. Between 2010 and 2012 we conducted a population-based cross-sectional study in Germany to determine HPV prevalence, genotype distribution and risk factors for HPV-infection in women aged 20-25 years. Women were recruited by a two-step cluster sampling approach. A home-based self-collection of cervicovaginal lavages was used. Specimens were analysed using a general primer GP5+/GP6+-based polymerase chain reaction and genotyped for 18 high-risk and 6 low-risk HPV- strains by Luminex-based multiplexed genotyping. Among 787 included women, 512 were not vaccinated against HPV. In the non-vaccinated population, HPV prevalence of any type was 38.1%, with HPV 16 (19.5%) being the most prevalent genotype. Prevalence of any high-risk type was 34.4%, and in 17.4% of all women, more than one genotype was identified. A higher number of lifetime sexual partners and low educational status were independently associated with HPV-infection. In 223 vaccinated women, prevalence of HPV 16/18 was significantly lower compared to non-vaccinated women (13.9% vs. 22.5%, p = 0.007). When stratifying by age groups, this difference was only significant in women aged 20-21 years, who at time of vaccination were on average younger and had less previous sexual contacts than women aged 22-25 years. We demonstrate a high prevalence of high-risk HPV genotypes in non-vaccinated women living in Germany that can be potentially prevented by vaccination. Probable first vaccination effects on the HPV prevalence were observed in women who were vaccinated at younger age. This finding reinforces the recommendation to vaccinate girls in early adolescence.
    BMC Infectious Diseases 02/2014; 14(1):87. DOI:10.1186/1471-2334-14-87 · 2.61 Impact Factor
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