Vaccine To Prevent Cervical Intraepithelial Neoplasia or Cervical Cancer in Younger Healthy Participants

NCT00128661 | Completed Phase 3 Results

• 4 other identifiers: CDR0000441189NCI-04-C-N191NCI-590299/009GSK-590299/009
• Study Type: interventional
• Target: 7,466
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer form forming, growing, or coming back. Vaccines may help the body build an effective immune response against human papillomavirus and may be effective in preventing cervical intraepithelial neoplasia or cervical cancer. It is not yet known whether human papillomavirus vaccine is more effective than hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer. PURPOSE: This randomized phase III trial is studying human papillomavirus vaccine to see how well it works compared to hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer in younger healthy participants.

Conditions

Cervical Cancer; Precancerous Condition

Keywords

cervical intraepithelial neoplasia grade 2; cervical cancer; cervical intraepithelial neoplasia grade 3

Outcome Measures

Primary Outcomes (1)

• Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.

  CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer. Preceding cervical cytology means the last cervical cytology specimen collected before the histopathology specimen was obtained. Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) by polymerase chain reaction (PCR) at Month 0 and Month 6 for the corresponding HPV-type.

  From Month 6 up to Month 48

Secondary Outcomes (19)

• Number of Cervical Infection With HPV16 or HPV18.

  From Month 6 up to Month 48

• Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type

  From Month 6 up to Month 48

• Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases

  From Month 6 up to Month 48

• Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.

  Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48

• Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort

  Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48

Study Arms (2)

Cervarix Group

EXPERIMENTAL

Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Biological: human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine

Havrix Group

ACTIVE COMPARATOR

Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Biological: hepatitis A inactivated virus vaccine

Interventions

human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine BIOLOGICAL

Three doses of Cervarix vaccine administered on a 0, 1, 6-month schedule

Cervarix Group

hepatitis A inactivated virus vaccine BIOLOGICAL

Three doses of Havrix vaccine administered on a 0, 1, 6-month schedule

Havrix Group

Eligibility Criteria

• Age: 18 Years - 25 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

DISEASE CHARACTERISTICS: •Healthy participants * Deemed to be in good general health by history and physical examination •Resident of Guanacaste Province of Costa Rica and surrounding areas * Must remain a resident for ≥ 6 months after the first study vaccination PATIENT CHARACTERISTICS: Age * 18 to 25 Performance status •Not specified Life expectancy •Not specified Hematopoietic •Not specified Hepatic * No history of chronic hepatitis requiring treatment * No acute or chronic clinically significant hepatic function abnormality by physical examination or laboratory findings * No known history of hepatitis A infection Renal * No history of kidney disease requiring treatment * No acute or chronic clinically significant kidney function abnormality by physical examination or laboratory findings Cardiovascular * No acute or chronic clinically significant cardiovascular function abnormality by physical examination or laboratory findings Pulmonary * No acute or chronic clinically significant pulmonary function abnormality by physical examination or laboratory findings Immunology * No history of allergic disease * No history of autoimmune disorder requiring treatment * No history of allergic reaction (e.g., difficulty breathing) to any vaccine * No suspected allergy or reaction likely to be exacerbated by a component of the study vaccines (e.g., 2-phenoxyethanol or neomycin) * No hypersensitivity to latex * No diagnosis or suspicion of any immunodeficient condition by medical history or physical examination Other * Not pregnant or nursing ◦No delivery within the past 3 months * Negative pregnancy test * Fertile patients must use effective contraception for 30 days before, during, and for 60 days after completion of study treatment * Able to speak or understand Spanish * Mentally competent * Able to undergo pelvic exam (i.e., no heavy bleeding \[menstruation or otherwise\] or heavy vaginal discharge) * No history of cancer requiring treatment * No history of diabetes requiring treatment * No history of other chronic conditions requiring treatment * No acute or chronic clinically significant neurologic function abnormality by physical examination or laboratory findings * No other acute disease * No fever ≥ 37.5º C PRIOR CONCURRENT THERAPY: Biologic therapy * More than 6 months since prior chronic administration (i.e., \> 14 days) of immune-modulating drugs * More than 90 days since prior immunoglobulins * More than 30 days since prior and no other concurrent investigational or non-registered vaccines * More than 30 days since prior registered vaccines * More than 8 days since prior routine meningococcal, hepatitis B, influenza, or diphtheria/tetanus vaccine * No prior vaccination against hepatitis A * No prior vaccination against human papillomavirus * No prior monophosphoryl lipid A or AS04 adjuvant Chemotherapy •Not specified Endocrine therapy * More than 6 months since prior chronic administration (i.e., \> 14 days) of corticosteroids (e.g., ≥ 0.5 mg/kg/day of prednisone or equivalent) * Concurrent inhaled or topical steroids allowed Radiotherapy •Not specified Surgery •No prior hysterectomy Other * More than 6 months since prior chronic administration (i.e., \> 14 days) of immunosuppressants * More than 30 days since prior and no other concurrent investigational or non-registered drugs

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

Proyecto Epidemiologico Guanacaste

Liberia, Costa Rica

Location

Related Publications (26)

• Kreimer AR, Rodriguez AC, Hildesheim A, Herrero R, Porras C, Schiffman M, Gonzalez P, Solomon D, Jimenez S, Schiller JT, Lowy DR, Quint W, Sherman ME, Schussler J, Wacholder S; CVT Vaccine Group. Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine. J Natl Cancer Inst. 2011 Oct 5;103(19):1444-51. doi: 10.1093/jnci/djr319. Epub 2011 Sep 9.

  PMID: 21908768 BACKGROUND

• Kemp TJ, Hildesheim A, Safaeian M, Dauner JG, Pan Y, Porras C, Schiller JT, Lowy DR, Herrero R, Pinto LA. HPV16/18 L1 VLP vaccine induces cross-neutralizing antibodies that may mediate cross-protection. Vaccine. 2011 Mar 3;29(11):2011-4. doi: 10.1016/j.vaccine.2011.01.001. Epub 2011 Jan 15.

  PMID: 21241731 BACKGROUND

• Sierra MS, Coto C, Porras C, Herrero R, Ugalde D, Sauer AN, Mora D, Montes CP, Schussler J, Hoffman AC, Hicks B, Ruggieri D, Cortes B, Hildesheim A, Kreimer AR, Wentzensen N, Dagnall C, Liu D. Validation of TypeSeq2, a Next-Generation-Based Sequencing Assay for the Detection of 46 Human Papillomavirus Genotypes, at the US National Cancer Institute and Costa Rica Laboratories. J Infect Dis. 2025 Dec 20;232(6):e906-e915. doi: 10.1093/infdis/jiaf369.

  PMID: 40796225 DERIVED

• Sierra MS, Carvajal LJ, Dull P, Herrero R, Schussler J, Hildesheim A, Schiller JT, Ocampo R, Liu D, Kreimer AR, Rodriguez AC, Lowy DR, Porras C; Costa Rica HPV Vaccine Trial (CVT) Group. Human papillomavirus type 16 and 18 viral clearance and progression to precancer among women aged 18-25 years enrolled in the Costa Rica HPV prophylactic vaccine trial (CVT). Vaccine. 2025 Mar 19;50:126841. doi: 10.1016/j.vaccine.2025.126841. Epub 2025 Feb 16.

  PMID: 39961279 DERIVED

• Befano B, Campos NG, Egemen D, Herrero R, Schiffman M, Porras C, Lowy DR, Rodriguez AC, Schiller JT, Ocampo R, Hildesheim A, Sampson JN, Das S, Kreimer AR, Cheung LC; Costa Rica HPV Vaccine Trial (CVT) Group. Estimating human papillomavirus vaccine efficacy from a single-arm trial: proof-of-principle in the Costa Rica Vaccine Trial. J Natl Cancer Inst. 2023 Jul 6;115(7):788-795. doi: 10.1093/jnci/djad064.

  PMID: 37040086 DERIVED

• Sierra MS, Tsang SH, Porras C, Herrero R, Sampson JN, Cortes B, Schussler J, Wagner S, Carvajal L, Quint W, Kreimer AR, Hu S, Rodriguez AC, Romero B, Hildesheim A; Costa Rica HPV Vaccine Trial (CVT) Group. Analysis of cervical HPV infections among unvaccinated young adult women to inform vaccine strategies in this age group: the Costa Rica HPV Vaccine Trial. Sex Transm Infect. 2022 Jul 16;99(3):180-6. doi: 10.1136/sextrans-2022-055434. Online ahead of print.

  PMID: 35842229 DERIVED

• Shing JZ, Hu S, Herrero R, Hildesheim A, Porras C, Sampson JN, Schussler J, Schiller JT, Lowy DR, Sierra MS, Carvajal L, Kreimer AR; Costa Rica HPV Vaccine Trial Group. Precancerous cervical lesions caused by non-vaccine-preventable HPV types after vaccination with the bivalent AS04-adjuvanted HPV vaccine: an analysis of the long-term follow-up study from the randomised Costa Rica HPV Vaccine Trial. Lancet Oncol. 2022 Jul;23(7):940-949. doi: 10.1016/S1470-2045(22)00291-1. Epub 2022 Jun 13.

  PMID: 35709811 DERIVED

• Usyk M, Schlecht NF, Pickering S, Williams L, Sollecito CC, Gradissimo A, Porras C, Safaeian M, Pinto L, Herrero R, Strickler HD, Viswanathan S, Nucci-Sack A, Diaz A; Costa Rica HPV Vaccine Trial (CVT) Group; Burk RD. molBV reveals immune landscape of bacterial vaginosis and predicts human papillomavirus infection natural history. Nat Commun. 2022 Jan 11;13(1):233. doi: 10.1038/s41467-021-27628-3.

  PMID: 35017496 DERIVED

• Usyk M, Zolnik CP, Castle PE, Porras C, Herrero R, Gradissimo A, Gonzalez P, Safaeian M, Schiffman M, Burk RD; Costa Rica HPV Vaccine Trial (CVT) Group. Cervicovaginal microbiome and natural history of HPV in a longitudinal study. PLoS Pathog. 2020 Mar 26;16(3):e1008376. doi: 10.1371/journal.ppat.1008376. eCollection 2020 Mar.

  PMID: 32214382 DERIVED

• Safaeian M, Castellsague X, Hildesheim A, Wacholder S, Schiffman MH, Bozonnat MC, Baril L, Rosillon D; Costa Rica HPV Vaccine Trial and the PATRICIA study groups. Risk of HPV-16/18 Infections and Associated Cervical Abnormalities in Women Seropositive for Naturally Acquired Antibodies: Pooled Analysis Based on Control Arms of Two Large Clinical Trials. J Infect Dis. 2018 Jun 5;218(1):84-94. doi: 10.1093/infdis/jiy112.

  PMID: 29718393 DERIVED

• Hildesheim A, Gonzalez P, Kreimer AR, Wacholder S, Schussler J, Rodriguez AC, Porras C, Schiffman M, Sidawy M, Schiller JT, Lowy DR, Herrero R; Costa Rica HPV Vaccine Trial (CVT) Group. Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment. Am J Obstet Gynecol. 2016 Aug;215(2):212.e1-212.e15. doi: 10.1016/j.ajog.2016.02.021. Epub 2016 Feb 16.

  PMID: 26892991 DERIVED

• Beachler DC, Kreimer AR, Schiffman M, Herrero R, Wacholder S, Rodriguez AC, Lowy DR, Porras C, Schiller JT, Quint W, Jimenez S, Safaeian M, Struijk L, Schussler J, Hildesheim A, Gonzalez P; Costa Rica HPV Vaccine Trial (CVT) Group. Multisite HPV16/18 Vaccine Efficacy Against Cervical, Anal, and Oral HPV Infection. J Natl Cancer Inst. 2015 Oct 14;108(1):djv302. doi: 10.1093/jnci/djv302. Print 2016 Jan.

  PMID: 26467666 DERIVED

• Panagiotou OA, Befano BL, Gonzalez P, Rodriguez AC, Herrero R, Schiller JT, Kreimer AR, Schiffman M, Hildesheim A, Wilcox AJ, Wacholder S; Costa Rica HPV Vaccine Trial (CVT) Group (see end of manuscript for full list of investigators). Effect of bivalent human papillomavirus vaccination on pregnancy outcomes: long term observational follow-up in the Costa Rica HPV Vaccine Trial. BMJ. 2015 Sep 7;351:h4358. doi: 10.1136/bmj.h4358.

  PMID: 26346155 DERIVED

• Kreimer AR, Struyf F, Del Rosario-Raymundo MR, Hildesheim A, Skinner SR, Wacholder S, Garland SM, Herrero R, David MP, Wheeler CM; Costa Rica Vaccine Trial Study Group Authors; Gonzalez P, Jimenez S, Lowy DR, Pinto LA, Porras C, Rodriguez AC, Safaeian M, Schiffman M, Schiller JT, Schussler J, Sherman ME; PATRICIA Study Group Authors; Bosch FX, Castellsague X, Chatterjee A, Chow SN, Descamps D, Diaz-Mitoma F, Dubin G, Germar MJ, Harper DM, Lewis DJ, Limson G, Naud P, Peters K, Poppe WA, Ramjattan B, Romanowski B, Salmeron J, Schwarz TF, Teixeira JC, Tjalma WA; HPV PATRICIA Principal Investigators/Co-Principal Investigator Collaborators; GSK Vaccines Clinical Study Support Group. Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials. Lancet Oncol. 2015 Jul;16(7):775-86. doi: 10.1016/S1470-2045(15)00047-9. Epub 2015 Jun 9.

  PMID: 26071347 DERIVED

• Gonzalez P, Hildesheim A, Herrero R, Katki H, Wacholder S, Porras C, Safaeian M, Jimenez S, Darragh TM, Cortes B, Befano B, Schiffman M, Carvajal L, Palefsky J, Schiller J, Ocampo R, Schussler J, Lowy D, Guillen D, Stoler MH, Quint W, Morales J, Avila C, Rodriguez AC, Kreimer AR; Costa Rica HPV Vaccine Trial (CVT) Group. Rationale and design of a long term follow-up study of women who did and did not receive HPV 16/18 vaccination in Guanacaste, Costa Rica. Vaccine. 2015 Apr 27;33(18):2141-51. doi: 10.1016/j.vaccine.2015.03.015. Epub 2015 Mar 18.

  PMID: 25796338 DERIVED

• Lang Kuhs KA, Porras C, Schiller JT, Rodriguez AC, Schiffman M, Gonzalez P, Wacholder S, Ghosh A, Li Y, Lowy DR, Kreimer AR, Poncelet S, Schussler J, Quint W, van Doorn LJ, Sherman ME, Sidawy M, Herrero R, Hildesheim A, Safaeian M; Costa Rica Vaccine Trial Group. Effect of different human papillomavirus serological and DNA criteria on vaccine efficacy estimates. Am J Epidemiol. 2014 Sep 15;180(6):599-607. doi: 10.1093/aje/kwu168. Epub 2014 Aug 19.

  PMID: 25139208 DERIVED

• Hildesheim A, Wacholder S, Catteau G, Struyf F, Dubin G, Herrero R; CVT Group. Efficacy of the HPV-16/18 vaccine: final according to protocol results from the blinded phase of the randomized Costa Rica HPV-16/18 vaccine trial. Vaccine. 2014 Sep 3;32(39):5087-97. doi: 10.1016/j.vaccine.2014.06.038. Epub 2014 Jul 10.

  PMID: 25018097 DERIVED

• Lang Kuhs KA, Gonzalez P, Rodriguez AC, van Doorn LJ, Schiffman M, Struijk L, Chen S, Quint W, Lowy DR, Porras C, DelVecchio C, Jimenez S, Safaeian M, Schiller JT, Wacholder S, Herrero R, Hildesheim A, Kreimer AR; Costa Rica Vaccine Trial Group. Reduced prevalence of vulvar HPV16/18 infection among women who received the HPV16/18 bivalent vaccine: a nested analysis within the Costa Rica Vaccine Trial. J Infect Dis. 2014 Dec 15;210(12):1890-9. doi: 10.1093/infdis/jiu357. Epub 2014 Jun 23.

  PMID: 24958910 DERIVED

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  PMID: 24014882 DERIVED

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MeSH Terms

Conditions

Uterine Cervical Neoplasms; Precancerous Conditions; Uterine Cervical Dysplasia

Interventions

human papillomavirus vaccine, L1 type 16, 18

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Limitations and Caveats

The following analysis "occurence of histopathologically confirmed CIN2+ cases associated with HPV16 or HPV18 infection was not performed, in accordance with the Statistical Analysis Plan submitted to the FDA.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2005
• First Posted: August 10, 2005
• Study Start: June 30, 2004
• Primary Completion: December 31, 2010
• Study Completion: December 31, 2010
• Last Updated: March 8, 2019
• Results First Posted: May 2, 2012

Record last verified: 2019-02

Locations

CO (1)