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ORIGINAL RESEARCH |
From the Departments of 1Obstetrics and Gynecology and 2Epidemiology, University of Washington, Seattle, Washington; 3Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta Georgia; 4Departments of Molecular Genetics & Microbiology, University of New Mexico, Albuquerque, New Mexico; 5Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; 6School of Nursing, University of California, Los Angeles, Los Angeles, California; 7Biologics Clinical Research and 8Biostatistics and Research Decision Sciences, Merck Research Laboratories, Blue Bell, Pennsylvania; and 9Department of Virus and Cell Biology, Merck Research Laboratories, West Point, Pennsylvania.
OBJECTIVE: Human papillomavirus (HPV) virus-like particle (VLP) vaccines have demonstrated effectiveness in preventing persistent HPV infections. Whether protection lasts longer than 18 months and, thus, impacts rates of cervical intraepithelial neoplasia (CIN) 2–3 has not yet been established. We present results from an HPV16 L1 VLP vaccine trial through 48 months.
METHODS: A total of 2,391 women, aged 16–23 years, participated in a randomized, double-blind, placebo-controlled trial. Either 40 µg HPV16 L1 VLP vaccine or placebo was given intramuscularly at day 1, month 2, and month 6. Genital samples for HPV16 DNA and Pap tests were obtained at day 1, month 7, and then 6-monthly through month 48. Colposcopy and cervical biopsies were performed if clinically indicated and at study exit. Serum HPV16 antibody titer was measured by radioimmunoassay.
RESULTS: Among 750 placebo recipients in the per protocol population, 12 women developed HPV16-related CIN2–3 (6 CIN2 and 6 CIN3). Among 755 vaccine recipients, there were no cases (vaccine efficacy 100%, 95% confidence interval [CI] 65–100%). There were 111 cases of persistent HPV16 infection in placebo recipients and 7 cases in vaccine recipients (vaccine efficacy 94%, 95% CI 88–98%). After immunization, HPV16 serum antibody geometric mean titers peaked at month 7 (1,519 milli-Merck units [mMU]/mL), declined through month 18 (202 mMU/mL), and remained relatively stable between month 30 and month 48 (128–150 mMU/mL).
CONCLUSION: The vaccine HPV16 L1 VLP provides high-level protection against persistent HPV16 infection and HPV16-related CIN2–3 for at least 3.5 years after immunization. Administration of L1 VLP vaccines targeting HPV16 is likely to reduce risk for cervical cancer.
LEVEL OF EVIDENCE: I
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