Gardasil HPV Vaccine Prevents High-Grade CIN

SAN FRANCISCO-In a large phase III study, a prophylactic human papillomavirus (HPV) vaccine prevented 100% of high-grade cervical precancers and noninvasive adenocarcinomas associated with HPV types 16 and 18. Laura Koutsky, PhD, of the University of Washington, Seattle, presented the results for the FUTURE II Steering Committee at a late-breaking abstract session of the Infectious Diseases Society of America annual meeting.

FUTURE II Trial

This analysis of the ongoing FUTURE II trial, a prospective, randomized, double-blind, placebo-controlled study, evaluated the incidence of HPV-16/18-related cervical intraepithelial neoplasia (CIN) 2/3 or cervical adenocarcinoma in situ (AIS) in more than 12,000 women aged 16 to 23 randomized to receive either quadrivalent HPV types 6, 11, 16, 18, recombinant vaccine (Gardasil), an investigational vaccine from Merck & Co., or placebo on day 1, month 2, and month 6. Women were enrolled from 90 study centers in 12 countries, including the United States.

The primary per protocol analysis of the trial evaluated women who received three doses of the Gardasil vaccine, had no major protocol violations, were HPV 16/18 seronegative on day 1 and HPV 16/18 DNA negative on day 1 through month 7. The analysis started 30 days after completion of the vaccination regimen and followed the women for an average of 17 months after completion of the study regimen.

In this group, Dr. Koutsky reported, there were no cases of CIN 2/3 or AIS associated with HPV 16/18 in those women receiving the vaccine (n = 5,301) vs 21 cases in those receiving placebo (n = 5,258) (P < .001).

Intention-to-Treat Analysis

A secondary interim modified-intention-to-treat analysis included the women in the primary analysis group plus women who received at least one dose of vaccine and were HPV 16/18 negative at day 1 (but may have become infected during the vaccination period). These women were followed for approximately 2 years.

The results showed a 97% efficacy rate for the vaccine (P < .001): One case of HPV-16/18-related CIN 2/3 or AIS occurred in the vaccine group (n = 5,736), compared with 36 in the placebo group (n = 5,766).

Dr. Koutsky noted that the vaccine was well tolerated, with injection site pain the most common vaccine-related adverse event and no discontinuations due to serious vaccine-related events.

Merck said in a press release that it remains on track to submit a Biologics License Application for Gardasil to the FDA in late 2005.