@article{a33cc977f9b949b58bb7869c9c0f9be8,
title = "The impact of quadrivalent human papillomavirus (HPV; Types 6, 11, 16, and 18) L1 virus-like particle vaccine on infection and disease due to oncogenic nonvaccine HPV types in generally HPV-naive women aged 16-26 years",
abstract = "Background. Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated. Methods. We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotying was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of-6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types. Results. Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/ 33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31. Conclusions. HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type. Trial registration. ClinicalTrials.gov identifiers: NCT00092521, NCT00092534, and NCT00092482.",
author = "Brown, {Darron R.} and Kjaer, {Susanne K.} and Kristj{\'a}n Sigurdsson and Iversen, {Ole Erik} and Mauricio, {Hernandez Avila} and Wheeler, {Cosette M.} and Gonzalo Perez and Koutsky, {Laura A.} and Tay, {Eng Hseon} and Patric{\'i}a Garcia and Ault, {Kevin A.} and Garland, {Suzanne M.} and Sepp Leodolter and Olsson, {Sven Eric} and Tang, {Grace W.K.} and Ferris, {Daron G.} and Jorma Paavonen and Marc Steben and Bosch, {F. Xavier} and Joakim Dillner and Joura, {Elmar A.} and Kurman, {Robert J.} and Slawomir Majewski and Nubia Mu{\~n}oz and Myers, {Evan R.} and Villa, {Luisa L.} and Taddeo, {Frank J.} and Christine Roberts and Amha Tadesse and Janine Bryan and Lupinacci, {Lisa C.} and Giacoletti, {Katherine E.D.} and Sings, {Heather L.} and Margaret James and Hesley, {Teresa M.} and Eliav Barra",
note = "Funding Information: Potential conflicts of interest. N.M. has received lecture fees, advisory board fees, and consultancy fees from Merck and Sanofi Pasteur MSD. S.-E.O. has received lecture fees from Merck. M.H.-A. has received lecture fees and grant support from Merck. O.-E.I. has received lecture fees from Merck and GlaxoSmithKline (GSK). C.M.W. has received funding through her institution to conduct HPV vaccine studies for GSK. K.A.A. has received consultancy and advisory board fees from Merck and has received funding through his institution to conduct HPV vaccine studies for Merck and GSK and nonvaccine clinical trials for Gen-Probe. F.X.B. has received lecture fees from Merck and GSK and has received funding through his institution to conduct HPV vaccine studies for GSK. J.P. has received consultancy fees, advisory board fees, and lecture fees from Merck. J.D. has received consultancy fees, lecture fees, and research grants from Merck and Sanofi Pasteur MSD. S.L. has received lecture fees from Merck and Sanofi Pasteur MSD. E.A.J. has received lecture fees from Merck, Sanofi Pasteur MSD, and GSK. S.K.K. has received consultancy fees and funding through her institution to conduct HPV vaccine studies for Sanofi Pasteur MSD and Digene. S.M.G. has received advisory board fees and grant support from Commonwealth Serum Laboratories and GSK and has received lecture fees from Merck. D.G.F. has received consultancy fees and funding through his institution to conduct HPV vaccine studies for GSK and lecture fees and consultancy fees from Merck. K.S. has received consultancy fees from Merck. S.M. has received lecture fees and advisory board fees from Merck. G.P. has received lecture fees and consultancy fees from Merck and Sanofi Pasteur MSD. D.R.B. has received lecture fees, advisory board fees, and intellectual property fees from Merck. M.S. has received lecture fees and grant support from Merck. Additionally, S.-E.O., C.M.W., M.H.-A., L.L.V., O.-E.I., G.W.K.T., F.X.B., J.P., J.D., E.H.T., S.L., E.A.J., S.K.K., G.P., D.G.F., K.S., M.S., L.A.K., and D.R.B. have received funding through their institutions to conduct HPV vaccine studies for Merck. F.J.T., C.R., A.T., J.B., L.C.L., K.E.D.G., H.L.S., M.J., T.M.H., and E.B. are employees of Merck and potentially own stock and/or stock options in the company.",
year = "2009",
month = apr,
day = "1",
doi = "10.1086/597307",
language = "English (US)",
volume = "199",
pages = "926--935",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "7",
}