Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials

• Published in: The Lancet (British edition) Vol. 369; no. 9574; pp. 1693 - 1702
• Main Authors: Joura, Elmar A, MD, Leodolter, Sepp, Prof, Hernandez-Avila, Mauricio, Prof, Wheeler, Cosette M, Prof, Perez, Gonzalo, MD, Koutsky, Laura A, Prof, Garland, Suzanne M, Prof, Harper, Diane M, Prof, Tang, Grace WK, Prof, Ferris, Daron G, Prof, Steben, Marc, Prof, Jones, Ronald W, MD, Bryan, Janine, PhD, Taddeo, Frank J, PhD, Bautista, Oliver M, PhD, Esser, Mark T, PhD, Sings, Heather L, PhD, Nelson, Micki, BS, Boslego, John W, MD, Sattler, Carlos, MD, Barr, Eliav, MD, Paavonen, Jorma, Prof
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 19.05.2007; Lancet; Elsevier Limited
• Subjects: Adolescent; Adult; Biological and medical sciences; Cervical cancer; Cervical Intraepithelial Neoplasia - prevention & control; Clinical trials; Data analysis; Deoxyribonucleic acid; Disease; DNA; Female; General aspects; Health facilities; Human papillomavirus; Humans; Immunization; Internal Medicine; Lesions; Medical sciences; Mortality; Multicenter Studies as Topic; Papillomaviridae - immunology; Papillomavirus Infections - prevention & control; Papillomavirus Vaccines; Prevention and actions; Public health. Hygiene; Public health. Hygiene-occupational medicine; Randomized Controlled Trials as Topic; Studies; Uterine Cervical Neoplasms - prevention & control; Vaccines; Womens health; Drug; Virus like particle; Human papillomavirus 6; Vagina; Vaccine; Papovaviridae; Papillomavirus; Virus; Medicine; Prevention; Immunoprophylaxis; Human papillomavirus 16; Human papillomavirus; Randomization; Clinical trial; Lesion
• DOI: 10.1016/S0140-6736(07)60777-6
• ISSN: 0140-6736

Summary Background Vulval and vaginal cancers among younger women are often related to infection with human papillomavirus (HPV). These cancers are preceded by high-grade vulval intraepithelial neoplasia (VIN2–3) and vaginal intraepithelial neoplasia (VaIN2–3). Our aim was to do a combined analysis of three randomised clinical trials to assess the effect of a prophylactic quadrivalent HPV vaccine on the incidence of these diseases. Methods 18 174 women (16–26 years) were enrolled and randomised to receive either quadrivalent HPV6/11/16/18 L1 virus-like-particle vaccine or placebo at day 1, and months 2 and 6. Individuals underwent detailed anogenital examination at day 1, 1 month after dose three, and at 6–12-month intervals for up to 48 months. Suspect genital lesions were biopsied and read by a panel of pathologists and vaccine HPV type-specific DNA testing was done. The primary endpoint was the combined incidence of VIN2–3 or VaIN2–3 associated with HPV16 or HPV18. Primary efficacy analyses were done in a per-protocol population. Findings The mean follow-up time was 3 years. Among women naive to HPV16 or HPV18 through 1 month after dose three (per-protocol population; vaccine n=7811; placebo n=7785), the vaccine was 100% effective (95% CI 72–100) against VIN2–3 or VaIN2–3 associated with HPV16 or HPV18. In the intention-to-treat population (which included 18 174 women who, at day 1, could have been infected with HPV16 or HPV18), vaccine efficacy against VIN2–3 or VaIN2–3 associated with HPV16 or HPV18 was 71% (37–88). The vaccine was 49% (18–69) effective against all VIN2–3 or VaIN2–3, irrespective of whether or not HPV DNA was detected in the lesion. The most common treatment-related adverse event was injection-site pain. Interpretation Prophylactic administration of quadrivalent HPV vaccine was effective in preventing high-grade vulval and vaginal lesions associated with HPV16 or HPV18 infection in women who were naive to these types before vaccination. With time, such vaccination could result in reduced rates of HPV-related vulval and vaginal cancers.