TAMPA The Cervarix vaccine provides protection for as long as 6.4 years against precancerous cervical lesions associated with the four most common cancer-causing types of human papillomavirus, data from an extended follow-up study show.
The initial placebo-controlled efficacy study of the GlaxoSmithKline vaccine included 1,113 women aged 1525 years at study entry, seronegative for HPV 16 and 18, and DNA negative for 14 other high-risk HPV types. From this group, 776 participants were included in the company-supported follow-up phase, Dr. Diane Harper reported at the annual meeting of the Society of Gynecologic Oncologists.
The follow-up population comprised 383 women given placebo and 393 who received three doses of the vaccine at 0, 1, and 6 months in the efficacy phase. HPV antibody titers were assessed, and cervical samples collected at 6-month intervals.
One hundred percent of the vaccinated follow-up phase participants were seropositive for both HPV 16 and 18 at 6.4 yearswith sustained antibody levels that were 10-fold higher than natural infection titers for HPV 16, and 8-fold higher than natural infection titers for HPV 18, said Dr. Harper of Dartmouth College, Lebanon, N.H.
"This is an amazing result that bodes well for women's protection against cervical cancer," she commented in an interview, explaining that "there is no wait time for memory cells to recognize and remanufacture antibodies with complete seropositivity and high antibody titers."
The antibodies are abundant and waiting to neutralize an infection, she said.
Vaccine efficacy at 6.4 years for all HPV 16 and 18 end points was substantial at 97% for incident infection, 100% for 6-month persistent infection, and 100% for 12-month persistent infection. Vaccine efficacy also was 100% against cervical intraepithelial neoplasia grades 1 and higher (CIN1+) and 2 and higher (CIN2+) associated with HPV 16 and 18.
There were no cases of CIN1+ or CIN2+ in the vaccinated group vs. 15 cases of CIN1+ and 9 cases of CIN2+ in the placebo group.
Efficacy was 72% against CIN2+ lesions independent of HPV status (5 vs. 17 cases in the vaccine and placebo groups, respectively). This is higher than the anticipated 50% based on the literature regarding the number of cases caused by the various types of HPV. Substantial cross-protection was maintained during the follow-up against incident infection with oncogenic HPV types 45 and 31, neither of which is covered by the vaccine.
Dr. Harper noted that HPV types 16, 18, 45, and 31 make up more than 80% of squamous cell carcinomas and more than 90% of adenocarcinomas associated with HPV. Thus, the level of protection Cervarix provided in this study would provide "a significant possible reduction in disease."
This is particularly noteworthy given the long follow-up, Dr. Harper said. That more than 90% of the original cohort was maintained for the follow-up study is "truly an amazing testament to the women who felt so strongly that these studies need to be done and are willing to continue to be followed for another 3 years up to 9.5 years," she added.
Cervarix, which would be a direct competitor to Merck & Co's Gardasil, is marketed in Europe and Australia, but it has not yet been approved in the United States. GlaxoSmithKline submitted a Biologics License Application to the Food and Drug Administration last year for the vaccine, but a decision on approval was delayed in December pending additional information from the company. The company anticipates approval this year.
Dr. Harper said that she received financial support for conducting the GlaxoSmithKline phase II and III trials of Cervarixand for conducting phase II and III clinical trials for Merck & Co.'s Gardasil. She also has received honorarium from both companies for consultations and speaking fees.
'This is an amazing result that bodes wellfor women's protection against cervical cancer.' DR. HARPER