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

Abstract

Background 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. Methods We randomized (3,727 HPV arm; 3,739 Control arm), vaccinated (HPV-16/18 or Hepatitis A) and followed (median 53.8 months) 7,466 healthy women aged 18-25 years. 5,312 women (2,635 HPV arm; 2,677 Control arm) were included in the according to protocol analysis for efficacy. The full cohort was evaluated for safety. Immunogenicity was considered on a subset of 354 (HPV-16) and 379 (HPV-18) women. HPV type was assessed by PCR on cytology specimens. Immunogenicity was assessed using ELISA and inhibition enzyme immunoassays. Disease outcomes were histologically confirmed. Vaccine efficacy and 95% confidence intervals (95%CI) were computed. Results Vaccine efficacy was 89.8% (95% CI: 39.5 - 99.5; N=11 events total) against HPV-16/18 associated CIN2+, 59.9% (95% CI: 20.7 - 80.8; N=39 events total) against CIN2+ associated with non-HPV-16/18 oncogenic HPVs and 61.4% (95% CI: 29.5-79.8; N=51 events total) against CIN2+ irrespective of HPV type. The vaccine had an acceptable safety profile and induced robust and long-lasting antibody responses. Conclusions Our findings confirm the high efficacy and immunogenicity of the HPV-16/18 vaccine against incident HPV infections and cervical disease associated with HPV-16/18 and other oncogenic HPV types. These results will serve as a benchmark to which we can compare future findings from ongoing extended follow-up of participants in the Costa Rica trial. Trial Registration Registered with clinicaltrials.gov: NCT00128661

Less than 3 doses of the HPV vaccine – Review of efficacy against virological and disease end points

“…18 A phase III randomized controlled study was conducted by the National Cancer Institute (NCI) of USA in the Guanacaste province of Costa Rica to evaluate the safety and efficacy of the bivalent vaccine in women aged 18 to 25 y 19 An ancillary posthoc analysis of the study evaluated the efficacy of fewer than 3 doses in the participants who received 2 doses (N D 422; 11.2% of the total participants) or a single dose (N D 196; 5.4% of the total participants) due to colposcopy referral, pregnancy, adverse events or non-compliance. 8 The vaccine efficacies against 12 months incident persistent HPV 16/18 infection after a median follow up of 4.2 y in the women negative for HPV 16/18 DNA at baseline were 80.9% (95% CI: 71.1 -87.7%), 84.1% (95% CI: 50.2 -96.3) and 100% (95% CI: 66.5 -100.0%) among the recipients of 3 doses, 2 doses and a single dose respectively.…”

HPV Vaccine: Updates and Highlights

“…Studies have consistently shown that HPV vaccines are highly immunogenic and effective in preventing HPV infections caused by the main oncogenic types and seem to have an excellent safety profile. Six large clinical trials (phase III) are classically cited as landmarks in the HPV vaccine literature, 3 of them for the 4-valent vaccine (FUTURE I, FUTURE II, and V501-020 study) [30-32], 2 for the 2-valent vaccine (Patricia Study and Guanacaste study) [33, 34], and one for the 9-valent vaccine (Broad Spectrum HPV Vaccine Study) [35]. All these trials were originally designed for women population, except the V501-020 Study [32], which included young men.…”

“…The FUTURE, Patricia and Guanacaste studies showed that the 2- and 4-valent vaccines are effective in preventing precursor lesions in the uterine cervix (CIN, cervical intraepithelial neoplasia) [30, 31, 33, 34]. In the HPV-naïve women, the efficacy rates of both vaccines are higher than 90% but reduce to near 50% in the overall population.…”

“…Palefsky et al [46] published the results of a specific cohort of the V501-020 study comprised men who had sex with men (aged 16–26 years) and found that the 4-valent vaccine efficacy in preventing AIN (related to HPV-6/11/16/18) was 77.5% among HPV-naïve men and 50.3% in the overall population. Although the Guanacaste study [34] did not directly assess AIN as an outcome, it evaluated HPV infection in the anus as a possible indicator of vaccine efficacy. The study underwent modifications throughout its development, with an additional collection of biological material from women in the 4-year study visit (vulva, anus, and mouth) and an application of survey on sexual habits.…”

“…The Guanacaste study [34] provided relevant information about the vaccine efficacy concerning oral HPV infection. At the 4-year study visit, 5,840 women provided oral specimens in order to evaluate the vaccine efficacy.…”