Persistent infection with human papilloma-virus (HPV) types 16 or 18 may be the major cause of cervical cancer. Initial studies of vaccines against HPV 16 and 18 indicate that 90 percent of infections can be prevented, but long-term immunogenicity is required to prevent malignant change. Harper and colleagues studied participants in a randomized controlled trial of HPV vaccines to determine the long-term effectiveness and safety of these vaccines.
The study included 776 women who received three doses of the bivalent HPV-16/18 virus-like particle AS04 vaccine or a placebo. During the follow-up period, the researchers monitored cervical sampling for HPV DNA testing, cervical cytology, and blood tests for immunologic responses. Colposcopy was performed if two specimens had atypical squamous cells of undetermined significance or if they had low-grade squamous intraepithelial lesions. Participants also reported any new onset of chronic disease, any condition that required a consultation by a physician or hospital admission, or any serious adverse effect experienced during the follow-up study. The average follow-up lasted 47.7 months.
In the treated group, the mean HPV-16 and HPV-18 titers peaked one month after the third immunization but slowly declined to a stable plateau at 18 months. Patients showed a strong positive immunologic response. However, after HPV-16 and HPV-18 infection, the mean titers were 36.3 and 26.5 units per mL, respectively. Following immunization, the mean titers were 17-fold and 14-fold higher in HPV-16 and HPV-18 infections, respectively, than for naturally acquired infection. The authors stress that the immunization was effective for preventing new infections.
By intention-to-treat analyses, only two out of 353 immunized women developed new HPV-16 infections, and two out of 352 women taking the placebo developed new mixed HPV-16/18 infections during the extended follow-up. In women assigned to placebo, the following new infections were documented: HPV-16, 21 infections; HPV-18, 11 infections; mixed HPV-16 and HPV-18, 28 infections. The authors calculated that the effectiveness of the vaccine was 95.8 percent against new HPV-16 infections, 100 percent against new HPV-18 infections, and 96.9 percent against mixed infections. The vaccine also showed similar effectiveness against both incident and persistent infections. Adverse events were more common in the placebo group than in the vaccine group (22 percent versus 14 percent), but the researchers note that minimal adverse events were not related to the immunization.
The authors conclude that the immunization provided effective protection against HPV-16 and HPV-18 infections. The degree of protection exceeded expectations and may be attributed to additional protection against other oncogenic HPV types such as HPV-45 and HPV-31. The vaccine protection appears to last for four to five years.