Quadrivalent Vaccine against Human Papillomavirus to Prevent Anogenital Diseases
Suzanne M. Garland, M.D., Mauricio Hernandez-Avila, M.D., Cosette M. Wheeler, Ph.D., Gonzalo Perez, M.D., Diane M. Harper, M.D., M.P.H., Sepp Leodolter, M.D., Grace W.K. Tang, M.D., Daron G. Ferris, M.D., Marc Steben, M.D., Janine Bryan, Ph.D., Frank J. Taddeo, Ph.D., Radha Railkar, Ph.D., Mark T. Esser, Ph.D., Heather L. Sings, Ph.D., Micki Nelson, B.S., John Boslego, M.D., Carlos Sattler, M.D., Eliav Barr, M.D., Laura A. Koutsky, Ph.D., for the Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE) I Investigators
Background A phase 3 trial was conducted to evaluate the efficacyof a prophylactic quadrivalent vaccine in preventing anogenitaldiseases associated with human papillomavirus (HPV) types 6,11, 16, and 18.
Methods In this randomized, placebo-controlled, double-blindtrial involving 5455 women between the ages of 16 and 24 years,we assigned 2723 women to receive vaccine and 2732 to receiveplacebo at day 1, month 2, and month 6. The coprimary compositeend points were the incidence of genital warts, vulvar or vaginalintraepithelial neoplasia, or cancer and the incidence of cervicalintraepithelial neoplasia, adenocarcinoma in situ, or cancerassociated with HPV type 6, 11, 16, or 18. Data for the primaryanalysis were collected for a per-protocol susceptible populationof women who had no virologic evidence of HPV type 6, 11, 16,or 18 through 1 month after administration of the third dose.
Results The women were followed for an average of 3 years afteradministration of the first dose. In the per-protocol population,those followed for vulvar, vaginal, or perianal disease included2261 women (83%) in the vaccine group and 2279 (83%) in theplacebo group. Those followed for cervical disease included2241 women (82%) in the vaccine group and 2258 (83%) in theplacebo group. Vaccine efficacy was 100% for each of the coprimaryend points. In an intention-to-treat analysis, including thosewith prevalent infection or disease caused by vaccine-type andnon–vaccine-type HPV, vaccination reduced the rate ofany vulvar or vaginal perianal lesions regardless of the causalHPV type by 34% (95% confidence interval [CI], 15 to 49), andthe rate of cervical lesions regardless of the causal HPV typeby 20% (95% CI, 8 to 31).
Conclusions The quadrivalent vaccine significantly reduced theincidence of HPV-associated anogenital diseases in young women.(ClinicalTrials.gov number, NCT00092521
[ClinicalTrials.gov]
.)
Source Information
From the Microbiology and Infectious Diseases Department, Royal Women's Hospital, and the Department of Obstetrics and Gynecology, University of Melbourne, Melbourne, Australia (S.M.G.); the National Institute of Public Health, Cuernavaca, Morelos, Mexico (M.H.-A.); the Departments of Molecular Genetics and Microbiology and Obstetrics and Gynecology, University of New Mexico, Albuquerque (C.M.W.); the National Research Center, Saludcoop, Bogotá, Colombia (G.P.); the Norris Cotton Cancer Center, Lebanon, NH (D.M.H.); the Departments of Obstetrics and Gynecology and Community and Family Medicine, Dartmouth Medical School, Hanover, NH (D.M.H.); the Department of Gynecology and Obstetrics, Women's Health Clinic, Medical University of Vienna, Vienna (S.L.); the Department of Obstetrics and Gynecology, University of Hong Kong, Hong Kong (G.W.K.T.); the Department of Family Medicine and Obstetrics and Gynecology, Medical College of Georgia, Augusta (D.G.F.); the Direction Risques Biologiques, Environnementaux et Occupationnels, Institut National de Santé Publique du Québec, Montreal (M.S.); Merck Research Laboratories, West Point, PA (J. Bryan, F.J.T., R.R., M.T.E., H.L.S., M.N., J. Boslego, C.S., E.B.); and the Department of Epidemiology, University of Washington, Seattle (L.A.K.).
Address reprint requests to Dr. Garland at the Microbiology and Infectious Diseases Department, Royal Women's Hospital, 132 Grattan St., Carlton, Victoria 3053, Australia, or at suzanne.garland{at}rch.org.au.
Human Papillomavirus Vaccine
Miller N. B., Raychaudhuri G., Toerner J. G., Suba E. J., Raab S. S., the Viet/American Cervical Cancer Prevention Project , Garland S. G., Koutsky L. A., Sawaya G. F., Smith-McCune K., Agosti J. M., Goldie S. J.
Extract |
Full Text |
PDF
N Engl J Med 2007;
357:1154-1156, Sep 13, 2007.
Correspondence
This article has been cited by other articles:
Munoz, N., Kjaer, S. K., Sigurdsson, K., Iversen, O.-E., Hernandez-Avila, M., Wheeler, C. M., Perez, G., Brown, D. R., Koutsky, L. A., Tay, E. H., Garcia, P. J., Ault, K. A., Garland, S. M., Leodolter, S., Olsson, S.-E., Tang, G. W. K., Ferris, D. G., Paavonen, J., Steben, M., Bosch, F. X., Dillner, J., Huh, W. K., Joura, E. A., Kurman, R. J., Majewski, S., Myers, E. R., Villa, L. L., Taddeo, F. J., Roberts, C., Tadesse, A., Bryan, J. T., Lupinacci, L. C., Giacoletti, K. E. D., Sings, H. L., James, M. K., Hesley, T. M., Barr, E., Haupt, R. M.
(2010). Impact of Human Papillomavirus (HPV)-6/11/16/18 Vaccine on All HPV-Associated Genital Diseases in Young Women. JNCI J Natl Cancer Inst
0: djp534v1-15
[Abstract][Full Text]
Plotkin, S. A.
(2009). Vaccines: the Fourth Century. CVI
16: 1709-1719
[Abstract][Full Text]
Pirotta, M, Ung, L, Stein, A, Conway, E L, Mast, T C, Fairley, C K, Garland, S
(2009). The psychosocial burden of human papillomavirus related disease and screening interventions. Sex. Transm. Infect.
85: 508-513
[Abstract][Full Text]
Dee, A., Howell, F.
(2009). A cost-utility analysis of adding a bivalent or quadrivalent HPV vaccine to the Irish cervical screening programme. Eur J Public Health
0: ckp141v2-ckp141
[Abstract][Full Text]
Kim, J. J., Ortendahl, J., Goldie, S. J.
(2009). Cost-Effectiveness of Human Papillomavirus Vaccination and Cervical Cancer Screening in Women Older Than 30 Years in the United States. ANN INTERN MED
151: 538-545
[Abstract][Full Text]
Kim, J. J, Goldie, S. J
(2009). Cost effectiveness analysis of including boys in a human papillomavirus vaccination programme in the United States. BMJ
339: b3884-b3884
[Abstract][Full Text]
Kjaer, S. K., Sigurdsson, K., Iversen, O.-E., Hernandez-Avila, M., Wheeler, C. M., Perez, G., Brown, D. R., Koutsky, L. A., Tay, E. H., Garcia, P., Ault, K. A., Garland, S. M., Leodolter, S., Olsson, S.-E., Tang, G. W.K., Ferris, D. G., Paavonen, J., Lehtinen, M., Steben, M., Bosch, F. X., Dillner, J., Joura, E. A., Majewski, S., Munoz, N., Myers, E. R., Villa, L. L., Taddeo, F. J., Roberts, C., Tadesse, A., Bryan, J., Maansson, R., Lu, S., Vuocolo, S., Hesley, T. M., Saah, A., Barr, E., Haupt, R. M.
(2009). A Pooled Analysis of Continued Prophylactic Efficacy of Quadrivalent Human Papillomavirus (Types 6/11/16/18) Vaccine against High-grade Cervical and External Genital Lesions. Cancer Prevention Research
2: 868-878
[Abstract][Full Text]
Gridelli, C., Rossi, A., Maione, P., Ferrara, M. L., Castaldo, V., Sacco, P. C.
(2009). Vaccines for the Treatment of Non-Small Cell Lung Cancer: A Renewed Anticancer Strategy. The Oncologist
14: 909-920
[Abstract][Full Text]
Slade, B. A., Leidel, L., Vellozzi, C., Woo, E. J., Hua, W., Sutherland, A., Izurieta, H. S., Ball, R., Miller, N., Braun, M. M., Markowitz, L. E., Iskander, J.
(2009). Postlicensure Safety Surveillance for Quadrivalent Human Papillomavirus Recombinant Vaccine. JAMA
302: 750-757
[Abstract][Full Text]
de Kok, I. M. C. M., van Ballegooijen, M., Habbema, J. D. F.
(2009). Cost-Effectiveness Analysis of Human Papillomavirus Vaccination in the Netherlands. JNCI J Natl Cancer Inst
101: 1083-1092
[Abstract][Full Text]
Kahn, J. A., Cooper, H. P., Vadaparampil, S. T., Pence, B. C., Weinberg, A. D., LoCoco, S. J., Rosenthal, S. L.
(2009). Human Papillomavirus Vaccine Recommendations and Agreement with Mandated Human Papillomavirus Vaccination for 11-to-12-Year-Old Girls: a Statewide Survey of Texas Physicians. Cancer Epidemiol. Biomarkers Prev.
18: 2325-2332
[Abstract][Full Text]
Poljak, M., Kocjan, B. J., Kovanda, A., Lunar, M. M., Lepej, S. Z., Planinic, A., Seme, K., Vince, A.
(2009). Human Papillomavirus Genotype Specificity of Hybrid Capture 2 Low-Risk Probe Cocktail. J. Clin. Microbiol.
47: 2611-2615
[Abstract][Full Text]
Kahn, J. A.
(2009). HPV Vaccination for the Prevention of Cervical Intraepithelial Neoplasia. NEJM
361: 271-278
[Full Text]
Iftner, T., Germ, L., Swoyer, R., Kjaer, S. K., Breugelmans, J. G., Munk, C., Stubenrauch, F., Antonello, J., Bryan, J. T., Taddeo, F. J.
(2009). Study Comparing Human Papillomavirus (HPV) Real-Time Multiplex PCR and Hybrid Capture II INNO-LiPA v2 HPV Genotyping PCR Assays. J. Clin. Microbiol.
47: 2106-2113
[Abstract][Full Text]
Garland, S. M., Insinga, R. P., Sings, H. L., Haupt, R. M., Joura, E. A.
(2009). Human Papillomavirus Infections and Vulvar Disease Development. Cancer Epidemiol. Biomarkers Prev.
18: 1777-1784
[Abstract][Full Text]
Goldstein, M. A., Goodman, A., del Carmen, M. G., Wilbur, D. C.
(2009). Case 10-2009 -- A 23-Year-Old Woman with an Abnormal Papanicolaou Smear. NEJM
360: 1337-1344
[Full Text]
Hoffman, J. M., Shah, N. D., Vermeulen, L. C., Doloresco, F., Martin, P. K., Blake, S., Matusiak, L., Hunkler, R. J., Schumock, G. T.
(2009). Projecting future drug expenditures--2009. Am J Health Syst Pharm
66: 237-257
[Abstract][Full Text]
Itoh, K., Yamada, A., Mine, T., Noguchi, M.
(2009). Recent Advances in Cancer Vaccines: An Overview. Jpn J Clin Oncol
39: 73-80
[Abstract][Full Text]
Garcia-Pineres, A. J., Hildesheim, A., Dodd, L., Kemp, T. J., Yang, J., Fullmer, B., Harro, C., Lowy, D. R., Lempicki, R. A., Pinto, L. A.
(2009). Gene Expression Patterns Induced by HPV-16 L1 Virus-Like Particles in Leukocytes from Vaccine Recipients. J. Immunol.
182: 1706-1729
[Abstract][Full Text]
Borja-Hart, N. L, Benavides, S., Christensen, C.
(2009). Human Papillomavirus Vaccine Safety in Pediatric Patients: An Evaluation of the Vaccine Adverse Event Reporting System. The Annals of Pharmacotherapy
43: 356-359
[Abstract][Full Text]
Handisurya, A., Gambhira, R., Schellenbacher, C., Shafti-Keramat, S., Forslund, O., Favre, M., Kirnbauer, R.
(2009). Serological relationship between cutaneous human papillomavirus types 5, 8 and 92. J. Gen. Virol.
90: 136-143
[Abstract][Full Text]
Arbyn, M., Benoy, I., Simoens, C., Bogers, J., Beutels, P., Depuydt, C.
(2009). Prevaccination Distribution of Human Papillomavirus Types in Women Attending at Cervical Cancer Screening in Belgium. Cancer Epidemiol. Biomarkers Prev.
18: 321-330
[Abstract][Full Text]
Ferris, D. G., Waller, J. L., Miller, J., Patel, P., Price, G. A., Jackson, L., Wilson, C.
(2009). Variables Associated With Human Papillomavirus (HPV) Vaccine Acceptance by Men. J Am Board Fam Med
22: 34-42
[Abstract][Full Text]
Castellsague, X., Cohet, C., Puig-Tintore, L. M, Acebes, L. O., Salinas, J., Martin, M. S., Breitscheidel, L., Remy, V.
(2009). Epidemiology and cost of treatment of genital warts in Spain. Eur J Public Health
19: 106-110
[Abstract][Full Text]
(2008). Vaccination against human papillomavirus. DTB
46: 89-93
[Abstract][Full Text]
Chaiyachati, K., Cinti, S. K., Kauffman, C. A., Riddell, J.
(2008). HIV-Infected Patients With Anal Carcinoma Who Subsequently Developed Oral Squamous Cell Carcinoma: Report of 2 Cases. J Int Assoc Physicians AIDS Care (Chic Ill)
7: 306-310
[Abstract]
Stanley, M.
(2008). HPV vaccines: are they the answer?. Br Med Bull
88: 59-74
[Abstract][Full Text]
van Zeeburg, H. J. T., Snijders, P. J. F., Wu, T., Gluckman, E., Soulier, J., Surralles, J., Castella, M., van der Wal, J. E., Wennerberg, J., Califano, J., Velleuer, E., Dietrich, R., Ebell, W., Bloemena, E., Joenje, H., Leemans, C. R., Brakenhoff, R. H.
(2008). Clinical and Molecular Characteristics of Squamous Cell Carcinomas From Fanconi Anemia Patients. JNCI J Natl Cancer Inst
100: 1649-1653
[Abstract][Full Text]
Hutchinson, D. J., Klein, K. C.
(2008). Human papillomavirus disease and vaccines. Am J Health Syst Pharm
65: 2105-2112
[Abstract][Full Text]
Castle, P. E., Porras, C., Quint, W. G., Rodriguez, A. C., Schiffman, M., Gravitt, P. E., Gonzalez, P., Katki, H. A., Silva, S., Freer, E., Van Doorn, L.-J., Jimenez, S., Herrero, R., Hildesheim, A., for the CVT Group,
(2008). Comparison of Two PCR-Based Human Papillomavirus Genotyping Methods. J. Clin. Microbiol.
46: 3437-3445
[Abstract][Full Text]
Blatter, M. M., Monk, B. J.
(2008). The Pediatrician's Role in Preventing Cervical Cancer. CLIN PEDIATR
47: 627-638
Kim, J. J., Goldie, S. J.
(2008). Health and Economic Implications of HPV Vaccination in the United States. NEJM
359: 821-832
[Abstract][Full Text]
LONGWORTH, D. L.
(2008). Update on infectious disease prevention: Human papillomavirus, hepatitis A. Cleveland Clinic Journal of Medicine
75: 402-410
[Abstract][Full Text]
Huang, C. M.
(2008). Human Papillomavirus and Vaccination. Mayo Clin Proc.
83: 701-707
[Abstract][Full Text]
Watanabe, H., Gehrke, S., Contassot, E., Roques, S., Tschopp, J., Friedmann, P. S., French, L. E., Gaide, O.
(2008). Danger Signaling through the Inflammasome Acts as a Master Switch between Tolerance and Sensitization. J. Immunol.
180: 5826-5832
[Abstract][Full Text]
Giuliano, A. R., Salmon, D.
(2008). The Case for a Gender-Neutral (Universal) Human Papillomavirus Vaccination Policy in the United States: Point. Cancer Epidemiol. Biomarkers Prev.
17: 805-808
[Full Text]
Lembo, D., Donalisio, M., Rusnati, M., Bugatti, A., Cornaglia, M., Cappello, P., Giovarelli, M., Oreste, P., Landolfo, S.
(2008). Sulfated K5 Escherichia coli Polysaccharide Derivatives as Wide-Range Inhibitors of Genital Types of Human Papillomavirus. Antimicrob. Agents Chemother.
52: 1374-1381
[Abstract][Full Text]
Hughes, D S, Powell, N, Fiander, A N
(2008). Will vaccination against human papillomavirus prevent eye disease? A review of the evidence. Br J Ophthalmol
92: 460-465
[Abstract][Full Text]
Hendrix, S. L.
(2008). Assessing Human Papillomavirus Vaccine Efficacy and Safety. JAOA: Journal of the American Osteopathic Association
108: S8-S12
[Abstract][Full Text]
Goldhaber-Fiebert, J. D., Stout, N. K., Salomon, J. A., Kuntz, K. M., Goldie, S. J.
(2008). Cost-Effectiveness of Cervical Cancer Screening With Human Papillomavirus DNA Testing and HPV-16,18 Vaccination. JNCI J Natl Cancer Inst
100: 308-320
[Abstract][Full Text]
Steben, M.
(2008). Do you approve of spending $300 million on HPV vaccination?: YES. cfp
54: 174-176
[Full Text]
Steben, M.
(2008). Approuvez-vous les 300 M $ pour la vaccination contre le VPH?: OUI. cfp
54: 178-180
[Full Text]
Outterson, K., Kesselheim, A. S.
(2008). Market-Based Licensing For HPV Vaccines In Developing Countries. Health Aff (Millwood)
27: 130-139
[Abstract][Full Text]
Kenter, G. G., Welters, M. J.P., Valentijn, A.R. P.M., Lowik, M. J.G., Berends-van der Meer, D. M.A., Vloon, A. P.G., Drijfhout, J. W., Wafelman, A. R., Oostendorp, J., Fleuren, G. J., Offringa, R., van der Burg, S. H., Melief, C. J.M.
(2008). Phase I Immunotherapeutic Trial with Long Peptides Spanning the E6 and E7 Sequences of High-Risk Human Papillomavirus 16 in End-Stage Cervical Cancer Patients Shows Low Toxicity and Robust Immunogenicity. Clin. Cancer Res.
14: 169-177
[Abstract][Full Text]
Ferenczy, A. MD
(2007). Vaccination against human papillomavirus. CMAJ
177: 1525-1525
[Full Text]
Toy, E. P.
(2007). Commentary. Reproductive Sciences
14: 736-736
Miller, N. B., Raychaudhuri, G., Toerner, J. G., Suba, E. J., Raab, S. S., the Viet/American Cervical Cancer Prevention Proje, , Garland, S. G., Koutsky, L. A., Sawaya, G. F., Smith-McCune, K., Agosti, J. M., Goldie, S. J.
(2007). Human Papillomavirus Vaccine. NEJM
357: 1154-1156
[Full Text]
Dawar, M. MD MHSc, Deeks, S. MD MHSc, Dobson, S. MD
(2007). Human papillomavirus vaccines launch a new era in cervical cancer prevention. CMAJ
177: 456-461
[Full Text]
Rambout, L. BScPhm, Hopkins, L. MD MSc, Hutton, B. MSc, Fergusson, D. PhD
(2007). Prophylactic vaccination against human papillomavirus infection and disease in women: a systematic review of randomized controlled trials. CMAJ
177: 469-479
[Abstract][Full Text]
Brisson, M. PhD, Van de Velde, N. MSc, De Wals, P. MD PhD, Boily, M.-C. PhD
(2007). Estimating the number needed to vaccinate to prevent diseases and death related to human papillomavirus infection. CMAJ
177: 464-468
[Abstract][Full Text]
Hildesheim, A., Herrero, R., Wacholder, S., Rodriguez, A. C., Solomon, D., Bratti, M. C., Schiller, J. T., Gonzalez, P., Dubin, G., Porras, C., Jimenez, S. E., Lowy, D. R., for the Costa Rican HPV Vaccine Trial Group,
(2007). Effect of Human Papillomavirus 16/18 L1 Viruslike Particle Vaccine Among Young Women With Preexisting Infection: A Randomized Trial. JAMA
298: 743-753
[Abstract][Full Text]
Markowitz, L. E.
(2007). HPV Vaccines Prophylactic, Not Therapeutic. JAMA
298: 805-806
[Full Text]
Fimbres, A., Barton, L. L.
(2007). How Effective Is the Quadrivalent HPV Vaccine at Preventing High-grade Cervical Lesions?. AAP Grand Rounds
18: 16-17
[Full Text]
(2007). HPV Vaccination Update: An Important Hurdle. JWatch Women's Health
2007: 2-2
[Full Text]
The FUTURE II Study Group,
(2007). Quadrivalent Vaccine against Human Papillomavirus to Prevent High-Grade Cervical Lesions. NEJM
356: 1915-1927
[Abstract][Full Text]
Baden, L. R., Curfman, G. D., Morrissey, S., Drazen, J. M.
(2007). Human Papillomavirus Vaccine -- Opportunity and Challenge. NEJM
356: 1990-1991
[Full Text]
Sawaya, G. F., Smith-McCune, K.
(2007). HPV Vaccination -- More Answers, More Questions. NEJM
356: 1991-1993
[Full Text]
(2007). Efficacy and Safety of the Quadrivalent HPV Vaccine. JWatch Infect. Diseases
2007: 1-1
[Full Text]
(2007). More Than an Ounce of Prevention for HPV. Journal Watch Dermatology
2007: 4-4
[Full Text]
(2007). HPV Vaccination: Data at Last. JWatch General
2007: 1-1
[Full Text]
Previous
