SEATTLE -- The quadrivalent human papilloma virus (HPV) vaccine (Gardasil) is nearly 100% effective in preventing disease from two major cancer-causing strains, two industry-sponsored studies reported.
SEATTLE, May 9 -- The quadrivalent human papilloma virus (HPV) vaccine (Gardasil) is nearly 100% effective in preventing disease from two major cancer-causing strains, two industry-sponsored studies reported.
The studies -- with a combined enrollment of more than 17,500 women -- prevented between 98% and 100% of lesions caused by HPV-16 and HPV-18 in participants who did not drop out for at least three years, the investigators said in the May 10 issue of the New England Journal of Medicine.
When all those who began the study were included -- including dropouts and those lost to follow-up -- the rates were lower, the researchers said.
Interim data from the studies -- Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) I and II -- were used to support licensing of the vaccine, which occurred in June 2006. Both studies were financed by Merck, the vaccine-maker.
Since the approval, the CDC has recommended that the vaccine be part of routine care for girls ages 11 and 12 and that women and girls from the ages of 13 through 26 should have access to the vaccine as a catch-up.
In the larger study -- FUTURE II -- researchers were looking at a composite endpoint of cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18, according to Laura Koutsky of the University of Washington, and colleagues.
After three years of follow-up, they analyzed a per-protocol population of 10,565 women without previous infection with HPV-16 or -18 (5,305 of them in the vaccine group) and found the vaccine was 98% effective in preventing the lesions contained in the primary endpoint.
The difference from placebo was significant at P
After three years of follow-up, when the researchers considered women who had no prior virologic evidence of any of the four types, they found the vaccine was 100% effective in preventing each of the endpoints.
On the other hand, in an intent-to-treat population -- including women with infection or disease caused by any type of HPV -- vaccination reduced the rate of any vulvar or vaginal perianal lesions by 34% and the rate of cervical lesions by 20%.
A key lesson from the studies is that the vaccine is highly effective in women who have never been infected with the four vaccine strains, but less so in a more exposed population, according to George Sawaya, M.D., and Karen Smith-McCune, M.D., Ph.D., both of the University of California San Francisco, in an editorial accompanying the two reports.
They said that the modest efficacy in the whole cohorts might also reflect the activity of oncogenic vaccine types not included in the vaccine.
"Policymakers, clinicians, and parents have a keen sense of urgency about HPV vaccination," they said, on the basis of the high efficacy of the vaccine against HPV types that cause life-threatening disease.
The vaccine appears to be safe so that "delaying vaccination may mean that many women will miss an opportunity for long-lasting protection," they said.
But questions about overall vaccine effectiveness, the duration of protection, and possible long-term adverse effects remain, they said, so that "a cautious approach may be warranted."
In particular, screening for cervical cancer should continue, they said, "given the cumulative lifetime risk of exposure to other oncogenic HPV types and the unknown duration of anti-HPV immunity."
The FUITURE II study was also supported by Merck. Ten of the authors report being either current or former employees of Merck and having an equity interest or holding stock options in the company. Several other authors report financial links to Merck, Gen-Probe, GlaxoSmithKline, Digene, Sanofi Pasteur, and Merck Sharp & Dohme. Indiana University and Merck have a confidential agreement that pays the university on the basis of certain landmarks regarding the HPV vaccine.