CoChat
Sign Up
Cited by 46Cervical Cancer and HPV ResearchGenital Health and DiseaseWomen's cancer prevention and management

Efficacy of quadrivalent human papillomavirus (types 6, 11, 16 and 18) vaccine (GARDASIL) in J apanese women aged 18–26 years

Open access
Yoshikawa, Hiroyuki, Ebihara, Keiko, Tanaka, Yoshiyuki, Noda, Kiichiro·2013·Cancer Science
DOI 10.1111/cas.12106PMC PMC7657183
Open this paper in CoChat — free account

Abstract

A randomized double‐blind placebo‐controlled phase II trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types most frequently associated with cervical cancer (types 16/18) and genital warts (types 6/11) in J apanese women aged 18–26 years. Participants were randomly assigned to either quadrivalent HPV (types 6/11/16/18) L 1 virus‐like particle vaccine (GARDASIL) (n = 509) or placebo (n = 512). Participants underwent regular gynecological examinations, cervicovaginal sampling for HPV DNA, testing for serum neutralizing antibodies to HPV and P apanicolau testing. The primary end‐point was the combined incidence of persistent infection with HPV types 6, 11, 16 or 18 and cervical or external genital disease (i.e. cervical intraepithelial neoplasia, cervical cancer or external genital lesions related to HPV 6, 11, 16 or 18. Primary analyses were done per protocol. Combined incidence of persistent infection or disease with HPV 6, 11, 16 or 18 fell by 87.6% (95% confidence interval [CI], 59.2–97.6; P < 0.001), with HPV 6 or 11 by 73.1% (95% CI, −1.1–97.3; P = 0.0756) and with HPV 16 or 18 by 94.5% (95% CI, 65.2–99.9; P < 0.001) in those assigned vaccine compared with those assigned placebo. The median duration of follow up after month 7 in subjects was 23 months. In addition, the vaccine was well tolerated in J apanese women aged 18–26 years. Quadrivalent HPV vaccine could significantly reduce the acquisition of infection and clinical disease caused by HPV types 6, 11, 16 and 18.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/cas.12106

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 27

  1. [1]1. Winer RL, Lee SK, Hughes JP, Adam DE, Kiviat NB, Koutsky LA. Genital human papillomavirus infection: incidence and risk factors in a cohort of female university students. Am J Epidemiol 2003; 157: 218–26. [DOI] [PubMed] [Google Scholar]
  2. [2]2. Fairley CK, Gay NJ, Forbes A, Abramson M, Garland SM. Hand‐genital transmission of genital warts? An analysis of prevalence data Epidemiol Infect 1995; 115: 169–76. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. [3]3. Herrero R, Castellsagué X, Pawlita M et al Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study. J Natl Cancer Inst 2003; 95: 1772–83. [DOI] [PubMed] [Google Scholar]
  4. [4]4. Yoshikawa H, Matsukura T, Yoshiike K, Yamamoto E, Kawana T, Mizuno M. Human papillomavirus DNA in female condylomata. Acta Obstet Gynecol Jpn 1985; 37: 1225–30. [PubMed] [Google Scholar]
  5. [6]6. Tokunaga H, Okamura C, Yaegashi N. Current status and therapeutic strategy of STD HPV, condyloma acuminatum. Obstet Gynecol Pract 2003; 52: 2111–20. [Google Scholar]
  6. [7]7. Walboomers JM, Jacobs MV, Manos MM et al Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999; 189: 12–9. [DOI] [PubMed] [Google Scholar]
  7. [8]8. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide. IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer, 2010. [Cited 26 Aug 2010.] Available from URL: http://globocan.iarc.fr. [Google Scholar]
  8. [9]9. Pagliusi SR, Aguado MT. Efficacy and other milestones for human papillomavirus vaccine introduction. Vaccine 2004; 23: 569–78. [DOI] [PubMed] [Google Scholar]
  9. [12]12. Mori M, Sagae S. Recent progress in epidemiologic research of uterine cancer. Gan To Kagaku Ryoho 2001; 28: 174–8. [PubMed] [Google Scholar]
  10. [13]13. Miura S, Matsumoto K, Oki A et al Do we need a different strategy for HPV screening and vaccination in East Asia? Int J Cancer 2006; 119: 2713–5. [DOI] [PubMed] [Google Scholar]
  11. [14]14. Onuki M, Matsumoto K, Satoh T et al Human papillomavirus infections among Japanese women: age‐related prevalence and type‐specific risk for cervical cancer. Cancer Sci 2009; 100: 1312–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. [15]15. Villa LL, Costa RL, Petta CA et al Prophylactic quadrivalent human papillomavirus (types 6, 11, 16 and 18) L1 virus‐like particle vaccine in young women: a randomised double‐blind placebo‐controlled multicentre phase II efficacy trial. Lancet Oncol 2005; 6: 271–8. [DOI] [PubMed] [Google Scholar]
  13. [17]17. Solomon D, Davey D, Kurman R et al The 2001 Bethesda system: terminology for reporting results of cervical cytology. JAMA 2002; 287: 2114–9. [DOI] [PubMed] [Google Scholar]
  14. [18]18. Wright TC Jr, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ. 2001 consensus guidelines for the management of women with cervical cytological abnormalities. JAMA 2002; 287: 2120–9. [DOI] [PubMed] [Google Scholar]
  15. [19]19. Stoler MH, Schiffman M. Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS‐LSIL triage study. JAMA 2004; 285: 1500–6. [DOI] [PubMed] [Google Scholar]
  16. [20]20. Opalka D, Lachman CE, MacMullen SA, Hall K, Leiserowitz GS. Simultaneous quantitation of antibodies to neutralizing epitopes on virus‐like particles for human papillomavirus types 6, 11, 16, and 18 by a multiplexed luminex assay. Clin Diagn Lab Immunol 2003; 10: 108–15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. [21]21. Christensen ND, Reed CA, Cladel NM, Hall K, Leiserowitz GS. Monoclonal antibodies to HPV‐6 L1 virus‐like particles identify conformational and linear neutralizing epitopes on HPV‐11 in addition to type‐specific epitopes on HPV‐6. Virology 1996; 224: 477–86. [DOI] [PubMed] [Google Scholar]
  18. [22]22. Christensen ND, Dillner J, Eklund C et al Surface conformational and linear epitopes on HPV‐16 and HPV‐18 L1 virus‐like particles as defined by monoclonal antibodies. Virology 1996; 223: 174–84. [DOI] [PubMed] [Google Scholar]
  19. [23]23. Wheeler CM, Kjaer SK, Sigurdsson K et al 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 sexually active women aged 16–26 years. J Infect Dis 2009; 199: 936–44. [DOI] [PubMed] [Google Scholar]
  20. [24]24. FUTURE II Study Group . Quadrivalent vaccine against human papillomavirus to prevent high‐grade cervical lesions. N Engl J Med 2007; 356: 1915–27. [DOI] [PubMed] [Google Scholar]
  21. [26]26. Christensen ND, Cladel NM, Reed CA et al Hybrid papillomavirus L1 molecules assemble into virus‐like particles that reconstitute conformational epitopes and induce neutralizing antibodies to distinct HPV types. Virology 2001; 291: 324–34. [DOI] [PubMed] [Google Scholar]
  22. [27]27. Dias D, Van Doren J, Schlottmann S et al Optimization and validation of a multiplexed luminex assay to quantify antibodies to neutralizing epitopes on human papillomaviruses 6, 11, 16, and 18. Clin Diagn Lab Immunol 2005; 12: 959–69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. [28]28. Joura EA, Kjaer SK, Wheeler CM et al HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine. Vaccine 2008; 26: 6844–51. [DOI] [PubMed] [Google Scholar]
  24. [29]29. Roberts C, Swoyer R, Bryan J. Evaluation of the HPV 18 antibody response in Gardasil® vaccinees after 48 mo using a pseudovirion neutralization assay. Hum Vaccin Immunother 2012; 8: 431–4. [DOI] [PubMed] [Google Scholar]
  25. [30]30. Olsson SE, Villa LL, Costa RL et al Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus‐like particle (VLP) vaccine. Vaccine 2007; 25: 4931–9. [DOI] [PubMed] [Google Scholar]
  26. [31]31. Fairley CK, Hocking JS, Gurrin LC, Chen MY, Donovan B, Bradshaw CS. Rapid decline in presentations of genital warts after the implementation of a national quadrivalent human papillomavirus vaccination programme for young women. Sex Transm Infect 2009; 85: 499–502. [DOI] [PubMed] [Google Scholar]
  27. [32]32. Brotherton JM, Fridman M, May CL, Chappell G, Saville AM, Gertig DM. Early effect of the HPV vaccination program on cervical abnormalities in Victoria, Australia: an ecological study. Lancet 2011; 377: 2085–92. [DOI] [PubMed] [Google Scholar] Articles from Cancer Science are provided here courtesy of Wiley

Cited by

Sorted by citations

Authors
Yoshikawa, H., Ebihara, K., Tanaka, Y., & Noda, K.
Affiliations
  • University of Tsukuba (JP)
  • MSD K.K. (Japan) (JP)
  • Kindai University (JP)
Corresponding author
Tanaka, Yoshiyuki
ORCID
Venue
Cancer Science
Publisher
Wiley
Published
2013-03-07
Volume
104
Issue
4
Pages
465-472
ISSN
  • 1347-9032 (ISSN-L)
  • 1349-7006
DOI
10.1111/cas.12106
PMC
PMC7657183
OpenAlex
W1972908686
Cited by
46
References
1
Citations by year
2025: 4 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 9 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 8
FWCI
3.16
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Cancer Science (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (23659770)
Topics
  • Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
  • Health Sciences › Medicine › Surgery › Genital Health and Disease
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Women's cancer prevention and management
Keywords
quadrivalent HPV vaccine, Gardasil, human papillomavirus, cervical cancer prevention, genital warts, persistent HPV infection, cervical intraepithelial neoplasia, young women, vaccine efficacy, Japanese women
MeSH terms
Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18, Adolescent, Adult, Uterine Cervical Dysplasia, Uterine Cervical Neoplasms, Double-Blind Method, Female, Humans, Papillomavirus Infections, Papillomavirus Vaccines, Young Adult, Vaccines, Virus-Like Particle

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review