An international group of investigators from Brazil, Europe, and the United States conducted a multicenter, randomized, double-blind, placebo-controlled study to investigate the safety (using a dose escalation design) and efficacy of a quadrivalent (types 6, 11, 16, and 18) human papillomavirus (HPV) L1 virus-like particle vaccine. A total of 1158 women, 16 to 24 years of age, received 3 intramuscular doses of 3 different strengths of the vaccine over a 6-month period. Exclusion criteria included pregnancy, a history of an abnormal Pap smear, and >4 male sex partners. Serial Pap smears, external genital, lateral vaginal, and cervical swabs for HPV PCR detection, and biopsy of external genital lesions were performed over a 36-month period. Primary study outcomes were: 1) persistent HPV infection with 1 of the 4 serotypes in the vaccine, defined as vaccine-type DNA in the cervicovaginal samples 7 months after vaccination at 2 or more consecutive visits or at the last visit before being lost to follow-up; and 2) HPV-associated disease, defined as cervical intraepithelial neoplasia, cervical, vulval, or vaginal cancer, or external genital warts with vaccine-HPV-type DNA detected. In this report, the efficacy of the low-dose vaccine preparation (that was as immunogenic as the other 2 higher dose level vaccines) and placebo were compared. A total of 277 women received active vaccine and 275 were administered placebo.
Over the 30-month follow-up period the combined incidence of persistent HPV infection or associated disease decreased by 90% (95% CI, 71–97) in women who received vaccine when compared to those who received placebo. The efficacy of the vaccine was 89% (95% CI, 73–96; P<.0001) in study patients who had received at least 1 dose of the vaccine. The vaccine was well tolerated.
Dr. Rathore has disclosed no financial relationships relevant to this commentary.
For pediatricians these are exciting times. Many diseases that had disastrous consequences in children are only discussed in the past tense and many others are rapidly disappearing.1 The recent recommendations for conjugate meningococcal vaccine2 and licensing of 2 acellular pertussis vaccines for adolescents provides hope for potentially conquering 2 more infectious diseases. The results of this study provide hope that HPV infection and the cancerous diseases it can cause may also soon be prevented. (See also