@article{e5f5599585244d8bb58f31b3d1b16ae7,
title = "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",
abstract = "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.",
author = "Joura, {Elmar A.} and Sepp Leodolter and Mauricio Hernandez-Avila and Wheeler, {Cosette M.} and Gonzalo Perez and Koutsky, {Laura A.} and Garland, {Suzanne M.} and Harper, {Diane M.} and Tang, {Grace WK} and Ferris, {Daron G.} and Marc Steben and Jones, {Ronald W.} and Janine Bryan and Taddeo, {Frank J.} and Bautista, {Oliver M.} and Esser, {Mark T.} and Sings, {Heather L.} and Micki Nelson and Boslego, {John W.} and Carlos Sattler and Eliav Barr and Jorma Paavonen",
note = "Funding Information: JP has received research grants from from Merck and Co through the University Central Hospital, Helsinki, to conduct clinical trial of this vaccine. He has received consulting fees or paid advisory boards from Merck & Co, and has received lecture fees from Merck and Co. LAK received grant support from her institution to do clinical trials for this vaccine. SMG has received advisory board fees and grant support from Commonwealth Serum Laboratories and GlaxoSmithKline, and lecture fees from Merck and Co. EAJ has a research contract with Merck Sharp and Dohme and GlaxoSmithKline and has received funding through the Medical University of Vienna, together with lecture fees and travel expenses from Sanofi Pasteur. SL has a research contract with Merck Sharp and Dohme, and has received funding through the Medical University of Vienna. MS has received consulting fees, advisory board fees, or lecture fees from Digene, Merck Frosst, GlaxoSmithKline, and Roche Diagnostics, and research grants from Merck Frosst and GlaxoSmithKline. MH-A has received fees and grant support from Merck and Co. DGF has acted as a consultant for Merck and Co and GlaxoSmithKline, and has acted as a speaker for Merck and Co. CMW has received research contracts for HPV vaccine studies from GlaxoSmithKline and Merck and Co. DMH has received study support for clinical trials, advisory board fees, and speaking fees from Merck and Co. GP has received research support, consulting fees, advisory board and lecture fees from Merck and Co. GWKT has received grant support through her institution to do clinical trials for this vaccine. JWB, FJT, OMB, MTE, HLS, JB, CS, EB, and MN are employees of Merck and Co and hold stock/stock options. RWJ declares no conflict of interest. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2007",
month = may,
day = "19",
doi = "10.1016/S0140-6736(07)60777-6",
language = "English (US)",
volume = "369",
pages = "1693--1702",
journal = "Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",
number = "9574",
}
