Study of the Safety of HPV Vaccine in Women 24-45 years – brought to you by MERCK

The Lancet

The Lancet, Volume 373, Issue 9679, Pages 1949 – 1957, 6 June 2009

Editors’ note: Sexually active women risk contracting human papillomavirus (HPV), which causes genital warts and cervical cancer. Although a quadrivalent HPV (types 6,11, 16, and 18) vaccine has shown efficacy in young women (ages 16–23 years), the efficacy of the same vaccine in older women (age 24–45 years) is unknown. This phase III trial was done to test the vaccine efficacy in the older age range of women with no history of genital warts or cervical cancer. This prophylactic HPV vaccine seems to be efficacious in women aged 24-45 years.

Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine in women aged 24—45 years: a randomised, double-blind trial

Prof Nubia Muñoz MD a , Ricardo Manalastas MD b, Punee Pitisuttithum MD c, Damrong Tresukosol MD d, Joseph Monsonego MD e, Kevin Ault MD f, Christine Clavel PhD g, Joaquin Luna MD a, Evan Myers MD h, Sara Hood BS i, Oliver Bautista PhD i, Janine Bryan PhD i, Frank J Taddeo PhD i, Mark T Esser PhD i, Scott Vuocolo PhD i, Richard M Haupt MD i, Eliav Barr MD i, Alfred Saah MD i

Summary

Background

Although the peak incidence of human papillomavirus (HPV) infection occurs in most populations within 5—10 years of first sexual experience, all women remain at risk for acquisition of HPV infections. We tested the safety, immunogenicity, and efficacy of the quadrivalent HPV (types 6, 11, 16, 18) L1 virus-like-particle vaccine in women aged 24—45 years.

Methods

Women aged 24—45 years with no history of genital warts or cervical disease were enrolled from community health centres, academic health centres, and primary health-care providers into an ongoing multicentre, parallel, randomised, placebo-controlled, double-blind study. Participants were allocated by computer-generated schedule to receive quadrivalent HPV vaccine (n=1911) or placebo (n=1908) at day 1, and months 2 and 6. All study site investigators and personnel, study participants, monitors, and central laboratory personnel were blinded to treatment allocation. Coprimary efficacy endpoints were 6 months’ or more duration of infection and cervical and external genital disease due to HPV 6, 11, 16, 18; and due to HPV 16 and 18 alone. Primary efficacy analyses were done in a per-protocol population, but intention-to-treat analyses were also undertaken. This study is registered with ClinicalTrials.gov, number NCT00090220.

Findings

1910 women received at least one dose of vaccine and 1907 at least one dose of placebo. In the per-protocol population, efficacy against the first coprimary endpoint (disease or infection related to HPV 6, 11, 16, and 18) was 90·5% (95% CI 73·7—97·5, four of 1615 cases in the vaccine group vs 41/1607 in the placebo group) and 83·1% (50·6—95·8, four of 1601 cases vs 23/1579 cases) against the second coprimary endpoint (disease or infection related to HPV 16 and 18 alone). In the intention-to-treat population, efficacy against the first coprimary endpoint was 30·9% (95% CI 11·1—46·5, 108/1886 cases vs 154/1883 cases) and against the second coprimary endpoint was 22·6% (−2·9 to 41·9, 90/1886 cases vs 115/1883 cases), since infection and disease were present at baseline. We recorded no vaccine-related serious adverse events.

Interpretation

The quadrivalent HPV vaccine is efficacious in women aged 24—45 years not infected with the relevant HPV types at enrolment.

Funding

Merck (USA).

PG

Author: Leslie Carol Botha

Author, publisher, radio talk show host and internationally recognized expert on women's hormone cycles. Social/political activist on Gardasil the HPV vaccine for adolescent girls. Co-author of "Understanding Your Mood, Mind and Hormone Cycle." Honorary advisory board member for the Foundation for the Study of Cycles and member of the Society for Menstrual Cycle Research.