An investigational vaccine against HPV ( Gardasil ) significantly reduced the combined incidence of HPV 6, 11, 16, or 18 infection and related diseases, including new cervical pre-cancers and genital warts compared to placebo.

The phase II, randomized, double-blind, placebo-controlled study evaluated the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus ( HPV ) types associated with 70% of cervical cancers ( types 16 and 18 ) and with 90% of genital warts ( types 6 and 11 ).

A total of 552 women between the ages of 16 and 23 were randomized to receive vaccine or placebo at day 1, month 2, and month 6.

The primary end point of the study was to assess the efficacy of the investigational vaccine in reducing the combined incidence of HPV 6, 11, 16, and 18 infections and related diseases, including cervical pre-cancers ( cervical intraepithelial neoplasia, or CIN ), cervical cancer, and/or external genital lesions ( genital warts ).

Over 2.5 years of follow-up after vaccination, HPV vaccine reduced the combined incidence of persistent infection from HPV 6, 11, 16, or 18 and related genital disease including new cervical pre-cancers and genital warts by 90 percent compared with placebo among women who were naïve to the relevant HPV types at baseline (p<0.0001).

Thirty-six cases of either disease, persistent infection, or detection of HPV on the last visit on record were seen in the placebo group compared to four in the group who received vaccine.

Of the four cases seen in the group who received vaccine, one was confirmed as persistent infection; in the other three cases HPV was detected on the last study visit but was not later confirmed as a persistent infection.

Adverse events related to the injection site were higher among those who received HPV vaccine compared with placebo recipients.
The most common injection site and systemic adverse events were pain and headache, respectively.
None of the subjects who received the vaccine discontinued the study due to an adverse experience.

Vaccination with Gardasil induced an immune response as measured by anti-HPV serum antibody titers.
Anti-HPV 6, 11, 16 and 18 geometric mean titers ( GMTs ) at the completion of the vaccine regimen ( month 7 ) were substantially higher among vaccinated women than among placebo-recipients with a previous history of natural HPV infection.
Although antibody levels among the women vaccinated with Gardasil started to decline after month 7, at month 36 they still remained at or above those observed in women in the placebo group who had an immune response to a previous natural HPV infection.

It is estimated that approximately 20 million American men and women are infected with HPV.
In some, the virus has been linked to cervical cancer, abnormal pap tests and genital warts.
In the United States, an estimated 10,370 new cases of cervical cancer will be diagnosed in 2005, and there will be an estimated 3,710 deaths from cervical cancer.
Genital warts are common: 500,000 to 1,000,000 cases in the United States alone.

Source: Lancet Oncology, 2005


XagenaMedicine2005