News Author: Laurie Barclay, MD

April 11, 2006 — Human papillomavirus (HPV) vaccine is highly immunogenic and safe and offers protection for up to 4.5 years, according to follow-up results of a randomized study published in the April 6 Early Online Publication issue of The Lancet.

"These findings set the stage for the widescale adoption of HPV vaccination for prevention of cervical cancer," lead author Diane M. Harper, MD, from Dartmouth Medical School in Lebanon, NH, said in a news release.

The authors note that effective vaccination against HPV 16 and HPV 18 to prevent cervical cancer requires a high degree of sustained protection against infection and precancerous lesions.

To evaluate the long-term efficacy, immunogenicity, and safety of a bivalent HPV-16/18 L1 virus-like particle AS04 vaccine, the investigators did a follow-up study of their multicenter, double-blind, randomized, placebo-controlled trial reported in 2004. The sample included 393 women who originally received all three 0.5-mL doses of bivalent HPV-16/18 virus-like particle AS04 vaccine, and 383 women who received placebo.

During the extended follow-up phase, more than 98% seropositivity was maintained for HPV-16/18 antibodies. The vaccine had significant efficacy against HPV-16 and HPV-18 endpoints, including incident infection (96.9%; 95% confidence interval [CI], 81.3 - 99.9); persistent infection: 6-month definition, 94.3% (95% CI, 63.2 - 99.9); 12-month definition, 100% (95% CI, 33.6 - 100).

Combined analysis of the initial efficacy and extended follow-up showed a vaccine efficacy of 100% (95% CI, 42.4 - 100) against cervical intraepithelial neoplasia lesions associated with vaccine types. However, there was also broad protection against cytohistologic outcomes beyond that anticipated for HPV-16/18, and protection against incident infection with HPV 45 and HPV 31. Safety profile was good over the long term.

"Up to 4.5 years, the HPV-16/18 L1 virus-like particle AS04 vaccine is highly immunogenic and safe, and induces a high degree of protection against HPV-16/18 infection and associated cervical lesions," the authors write. "There is also evidence of cross protection."

The main study limitation is the few observations of cervical intraepithelial neoplasia in the extended follow-up phase, which may reflect the time required to develop true persistent high-grade cervical dysplasia.

GlaxoSmithKline Biologicals funded and coordinated this study, and employs 4 of its authors. Several other authors have disclosed various financial relationships with GlaxoSmithKline Biologicals, Merck & Co, 3M, Pfizer, Roche, and/or Schering.