Evaluation of Long Term Immunity Following HPV Vaccination

NCT02276521 | Completed DMC

• 1 other identifier: 2014.5.FNRERC.5.SU
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

In Fiji, cervical cancer is the second most frequent cancer and the highest cause of cancer mortality in women. In 2008/9, the Ministry of Health in Fiji accepted a donation of 110,000 doses of quadrivalent HPV vaccine, Gardasil® based on the high cervical cancer disease burden. There was enough vaccine to vaccinate all girls aged 9-12 years (30,338 girls) with a three-dose schedule, but not all girls received three doses of the vaccine. This means those girls that received reduced doses may not be fully protected against the HPV genotypes present in the Gardasil®. While HPV vaccines are highly immunogenic and efficacious in the licensed three-dose schedule, there is limited information about the effectiveness of reduced dose schedules in terms of immunogenicity and memory. There is growing evidence from other studies that two doses of HPV vaccine may be sufficient for protection. Reduced schedules would be of benefit in Fiji due to improved costs and logistics. This study will examine whether one or two doses of HPV vaccine provide similar immunological evidence of long-term protection to the standard three-dose schedule in terms of antibody titres to the genotypes present in the Gardasil®. To compare immunological memory responses between dosage groups, a dose of Cervarix ® will be administered to all girls so that the magnitude of the memory responses can be measured.

Conditions

Cervical Cancer; Anogenital Warts

Outcome Measures

Primary Outcomes (1)

• GMCs of HPV- specific antibody titres against HPV 6, 11, 16 and 18

  6 months

Secondary Outcomes (3)

• GMCs of HPV- specific antibody titres against HPV 6, 11, 16 and 18 one month post Cervarix®

  6 months

• Number of HPV- specific memory B- and T- cells against HPV 6, 11, 16 and 18 pre and one month post Cervarix®

  11 months

• Fold change in the gene expression profiles in immune cells both pre- and one month post Cervarix®

  11 months

Study Arms (4)

Zero dose group

Participants that did not received any HPV vaccine previously.

Biological: Cervarix®

One dose group

Participants that received one dose of Gardasil® vaccine 5-6 years ago from a vaccination campaign.

Biological: Cervarix®

Two dose group

Participants that received two dose of Gardasil® vaccine 5-6 years ago from a vaccination campaign.

Biological: Cervarix®

Three dose group

Participants that received three dose of Gardasil® vaccine 5-6 years ago from a vaccination campaign.

Biological: Cervarix®

Interventions

Cervarix® BIOLOGICAL

All groups will received one dose of Cervarix® vaccine

One dose group; Three dose group; Two dose group; Zero dose group

Eligibility Criteria

• Age: 15 Years - 17 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

In 2008/9, the MoH in Fiji accepted a one-off donation of 110,000 doses of Gardasil® vaccine, which was enough to vaccinate four birth cohorts of girls (30,338 girls aged 9-12 years) with a three-dose schedule via a school-based program. However, not all the girls received the full-recommended three-dose schedule, mainly due to absence from school on the day the school health team were visiting. The coverage following the initial and the subsequent mop-up campaign was: 62%, 56%, and 55% for doses one, two, and three respectively. The girls that received different doses of Gardasil® vaccine in Suva area who are potentially contactable in this study are 676 (three doses), 204 (two doses) and 116 (one dose), demonstrating feasibility of recruitment.

You may qualify if:

• Girls who live in Suva and were previously vaccinated with one, two or three Gardasil® doses or were eligible but did not receive Gardasil® vaccine in the 2008/9 campaign will be eligible for the study.

You may not qualify if:

• Any participant who had anaphylaxis following a previous dose of the vaccine, anaphylaxis to any vaccine component, or possible pregnancy will be excluded from this study.
• In addition, any participant whose dates of previous Gardasil® vaccination are uncertain, or has received Cervarix® vaccine previously, or has an axillary temperature greater than 38°C will be excluded from this study.

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead
• Department of Foregin Affairs and Trade, Australia: collaborator
• Ministry of Health, Fiji: collaborator
• The Royal Women Hospital: collaborator
• Colonial War Memorial Hospital: collaborator

Study Sites (1)

Colonial War Memorial Hospital

Suva, Fiji

Location

Related Publications (35)

• Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4.

  PMID: 21296855 BACKGROUND

• de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, Tous S, Felix A, Bravo LE, Shin HR, Vallejos CS, de Ruiz PA, Lima MA, Guimera N, Clavero O, Alejo M, Llombart-Bosch A, Cheng-Yang C, Tatti SA, Kasamatsu E, Iljazovic E, Odida M, Prado R, Seoud M, Grce M, Usubutun A, Jain A, Suarez GA, Lombardi LE, Banjo A, Menendez C, Domingo EJ, Velasco J, Nessa A, Chichareon SC, Qiao YL, Lerma E, Garland SM, Sasagawa T, Ferrera A, Hammouda D, Mariani L, Pelayo A, Steiner I, Oliva E, Meijer CJ, Al-Jassar WF, Cruz E, Wright TC, Puras A, Llave CL, Tzardi M, Agorastos T, Garcia-Barriola V, Clavel C, Ordi J, Andujar M, Castellsague X, Sanchez GI, Nowakowski AM, Bornstein J, Munoz N, Bosch FX; Retrospective International Survey and HPV Time Trends Study Group. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010 Nov;11(11):1048-56. doi: 10.1016/S1470-2045(10)70230-8. Epub 2010 Oct 15.

  PMID: 20952254 BACKGROUND

• Winer RL, Kiviat NB, Hughes JP, Adam DE, Lee SK, Kuypers JM, Koutsky LA. Development and duration of human papillomavirus lesions, after initial infection. J Infect Dis. 2005 Mar 1;191(5):731-8. doi: 10.1086/427557. Epub 2005 Jan 21.

  PMID: 15688287 BACKGROUND

• Teissier S, Pang CL, Thierry F. The E2F5 repressor is an activator of E6/E7 transcription and of the S-phase entry in HPV18-associated cells. Oncogene. 2010 Sep 9;29(36):5061-70. doi: 10.1038/onc.2010.246. Epub 2010 Jul 19.

  PMID: 20639900 BACKGROUND

• Sellors JW, Karwalajtys TL, Kaczorowski J, Mahony JB, Lytwyn A, Chong S, Sparrow J, Lorincz A; Survey of HPV in Ontario Women Group. Incidence, clearance and predictors of human papillomavirus infection in women. CMAJ. 2003 Feb 18;168(4):421-5.

  PMID: 12591782 BACKGROUND

• Kanodia S, Fahey LM, Kast WM. Mechanisms used by human papillomaviruses to escape the host immune response. Curr Cancer Drug Targets. 2007 Feb;7(1):79-89. doi: 10.2174/156800907780006869.

  PMID: 17305480 BACKGROUND

• Stanley M. Immune responses to human papillomavirus. Vaccine. 2006 Mar 30;24 Suppl 1:S16-22. doi: 10.1016/j.vaccine.2005.09.002.

  PMID: 16219398 BACKGROUND

• Kirnbauer R, Hubbert NL, Wheeler CM, Becker TM, Lowy DR, Schiller JT. A virus-like particle enzyme-linked immunosorbent assay detects serum antibodies in a majority of women infected with human papillomavirus type 16. J Natl Cancer Inst. 1994 Apr 6;86(7):494-9. doi: 10.1093/jnci/86.7.494.

  PMID: 8133532 BACKGROUND

• Who. Human papillomavirus vaccines: WHO position paper. Biologicals. 2009 Oct;37(5):338-44. doi: 10.1016/j.biologicals.2009.04.005. Epub 2009 Jun 13. No abstract available.

  PMID: 19525124 BACKGROUND

• Garcon N, Wettendorff M, Van Mechelen M. Role of AS04 in human papillomavirus vaccine: mode of action and clinical profile. Expert Opin Biol Ther. 2011 May;11(5):667-77. doi: 10.1517/14712598.2011.573624. Epub 2011 Apr 4.

  PMID: 21457083 BACKGROUND

• Joura EA, Leodolter S, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, Garland SM, Harper DM, Tang GW, Ferris DG, Steben M, Jones RW, Bryan J, Taddeo FJ, Bautista OM, Esser MT, Sings HL, Nelson M, Boslego JW, Sattler C, Barr E, Paavonen J. 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. Lancet. 2007 May 19;369(9574):1693-702. doi: 10.1016/S0140-6736(07)60777-6.

  PMID: 17512854 BACKGROUND

• FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007 May 10;356(19):1915-27. doi: 10.1056/NEJMoa061741.

  PMID: 17494925 BACKGROUND

• Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, Zahaf T, Innis B, Naud P, De Carvalho NS, Roteli-Martins CM, Teixeira J, Blatter MM, Korn AP, Quint W, Dubin G; GlaxoSmithKline HPV Vaccine Study Group. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet. 2004 Nov 13-19;364(9447):1757-65. doi: 10.1016/S0140-6736(04)17398-4.

  PMID: 15541448 BACKGROUND

• Villa LL, Costa RL, Petta CA, Andrade RP, Paavonen J, Iversen OE, Olsson SE, Hoye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, Krogh Gv, Lehtinen M, Malm C, Tamms GM, Giacoletti K, Lupinacci L, Railkar R, Taddeo FJ, Bryan J, Esser MT, Sings HL, Saah AJ, Barr E. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer. 2006 Dec 4;95(11):1459-66. doi: 10.1038/sj.bjc.6603469. Epub 2006 Nov 21.

  PMID: 17117182 BACKGROUND

• Villa LL, Ault KA, Giuliano AR, Costa RL, Petta CA, Andrade RP, Brown DR, Ferenczy A, Harper DM, Koutsky LA, Kurman RJ, Lehtinen M, Malm C, Olsson SE, Ronnett BM, Skjeldestad FE, Steinwall M, Stoler MH, Wheeler CM, Taddeo FJ, Yu J, Lupinacci L, Railkar R, Marchese R, Esser MT, Bryan J, Jansen KU, Sings HL, Tamms GM, Saah AJ, Barr E. Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18. Vaccine. 2006 Jul 7;24(27-28):5571-83. doi: 10.1016/j.vaccine.2006.04.068. Epub 2006 May 15.

  PMID: 16753240 BACKGROUND

• Giannini SL, Hanon E, Moris P, Van Mechelen M, Morel S, Dessy F, Fourneau MA, Colau B, Suzich J, Losonksy G, Martin MT, Dubin G, Wettendorff MA. Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. Vaccine. 2006 Aug 14;24(33-34):5937-49. doi: 10.1016/j.vaccine.2006.06.005. Epub 2006 Jun 19.

  PMID: 16828940 BACKGROUND

• Harper DM, Franco EL, Wheeler CM, Moscicki AB, Romanowski B, Roteli-Martins CM, Jenkins D, Schuind A, Costa Clemens SA, Dubin G; HPV Vaccine Study group. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet. 2006 Apr 15;367(9518):1247-55. doi: 10.1016/S0140-6736(06)68439-0.

  PMID: 16631880 BACKGROUND

• Rowhani-Rahbar A, Alvarez FB, Bryan JT, Hughes JP, Hawes SE, Weiss NS, Koutsky LA. Evidence of immune memory 8.5 years following administration of a prophylactic human papillomavirus type 16 vaccine. J Clin Virol. 2012 Mar;53(3):239-43. doi: 10.1016/j.jcv.2011.12.009. Epub 2011 Dec 30.

  PMID: 22209292 BACKGROUND

• Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR, Wheeler CM, Koutsky LA, Malm C, Lehtinen M, Skjeldestad FE, Olsson SE, Steinwall M, Brown DR, Kurman RJ, Ronnett BM, Stoler MH, Ferenczy A, Harper DM, Tamms GM, Yu J, Lupinacci L, Railkar R, Taddeo FJ, Jansen KU, Esser MT, Sings HL, Saah AJ, Barr E. 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 May;6(5):271-8. doi: 10.1016/S1470-2045(05)70101-7.

  PMID: 15863374 BACKGROUND

• Wrammert J, Ahmed R. Maintenance of serological memory. Biol Chem. 2008 May;389(5):537-9. doi: 10.1515/bc.2008.066.

  PMID: 18953719 BACKGROUND

• Ohlschlager P, Osen W, Dell K, Faath S, Garcea RL, Jochmus I, Muller M, Pawlita M, Schafer K, Sehr P, Staib C, Sutter G, Gissmann L. Human papillomavirus type 16 L1 capsomeres induce L1-specific cytotoxic T lymphocytes and tumor regression in C57BL/6 mice. J Virol. 2003 Apr;77(8):4635-45. doi: 10.1128/jvi.77.8.4635-4645.2003.

  PMID: 12663770 BACKGROUND

• Mariani L, Venuti A. HPV vaccine: an overview of immune response, clinical protection, and new approaches for the future. J Transl Med. 2010 Oct 27;8:105. doi: 10.1186/1479-5876-8-105.

  PMID: 20979636 BACKGROUND

• 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

• Romanowski B, Schwarz TF, Ferguson LM, Peters K, Dionne M, Schulze K, Ramjattan B, Hillemanns P, Catteau G, Dobbelaere K, Schuind A, Descamps D. Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose schedule compared with the licensed 3-dose schedule: results from a randomized study. Hum Vaccin. 2011 Dec;7(12):1374-86. doi: 10.4161/hv.7.12.18322. Epub 2011 Dec 1.

  PMID: 22048171 BACKGROUND

• Dobson SR, McNeil S, Dionne M, Dawar M, Ogilvie G, Krajden M, Sauvageau C, Scheifele DW, Kollmann TR, Halperin SA, Langley JM, Bettinger JA, Singer J, Money D, Miller D, Naus M, Marra F, Young E. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA. 2013 May 1;309(17):1793-802. doi: 10.1001/jama.2013.1625.

  PMID: 23632723 BACKGROUND

• Olsson SE, Villa LL, Costa RL, Petta CA, Andrade RP, Malm C, Iversen OE, Hoye J, Steinwall M, Riis-Johannessen G, Andersson-Ellstrom A, Elfgren K, von Krogh G, Lehtinen M, Paavonen J, Tamms GM, Giacoletti K, Lupinacci L, Esser MT, Vuocolo SC, Saah AJ, Barr E. 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 Jun 21;25(26):4931-9. doi: 10.1016/j.vaccine.2007.03.049. Epub 2007 Apr 20.

  PMID: 17499406 BACKGROUND

• Smolen KK, Gelinas L, Franzen L, Dobson S, Dawar M, Ogilvie G, Krajden M, Fortuno ES 3rd, Kollmann TR. Age of recipient and number of doses differentially impact human B and T cell immune memory responses to HPV vaccination. Vaccine. 2012 May 21;30(24):3572-9. doi: 10.1016/j.vaccine.2012.03.051. Epub 2012 Mar 31.

  PMID: 22469863 BACKGROUND

• Dauner JG, Pan Y, Hildesheim A, Harro C, Pinto LA. Characterization of the HPV-specific memory B cell and systemic antibody responses in women receiving an unadjuvanted HPV16 L1 VLP vaccine. Vaccine. 2010 Jul 26;28(33):5407-13. doi: 10.1016/j.vaccine.2010.06.018. Epub 2010 Jun 17.

  PMID: 20591543 BACKGROUND

• Law I, Fong JJ, Buadromo EM, Samuela J, Patel MS, Garland SM, Mulholland EK, Russell FM. The high burden of cervical cancer in Fiji, 2004-07. Sex Health. 2013 May;10(2):171-8. doi: 10.1071/SH12135.

  PMID: 23557630 BACKGROUND

• Tabrizi SN, Law I, Buadromo E, Stevens MP, Fong J, Samuela J, Patel M, Mulholland EK, Russell FM, Garland SM. Human papillomavirus genotype prevalence in cervical biopsies from women diagnosed with cervical intraepithelial neoplasia or cervical cancer in Fiji. Sex Health. 2011 Sep;8(3):338-42. doi: 10.1071/SH10083.

  PMID: 21851773 BACKGROUND

• Neuzil KM, Canh DG, Thiem VD, Janmohamed A, Huong VM, Tang Y, Diep NT, Tsu V, LaMontagne DS. Immunogenicity and reactogenicity of alternative schedules of HPV vaccine in Vietnam: a cluster randomized noninferiority trial. JAMA. 2011 Apr 13;305(14):1424-31. doi: 10.1001/jama.2011.407.

  PMID: 21486975 BACKGROUND

• Centers for Disease Control and Prevention (CDC). FDA licensure of bivalent human papillomavirus vaccine (HPV2, Cervarix) for use in females and updated HPV vaccination recommendations from the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2010 May 28;59(20):626-9.

  PMID: 20508593 BACKGROUND

• Descamps D, Hardt K, Spiessens B, Izurieta P, Verstraeten T, Breuer T, Dubin G. Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials. Hum Vaccin. 2009 May;5(5):332-40. doi: 10.4161/hv.5.5.7211. Epub 2009 May 20.

  PMID: 19221517 BACKGROUND

• Gold MS, McIntyre P. Human papillomavirus vaccine safety in Australia: experience to date and issues for surveillance. Sex Health. 2010 Sep;7(3):320-4. doi: 10.1071/SH09153.

  PMID: 20719221 BACKGROUND

• Tabrizi SN, Frazer IH, Garland SM. Serologic response to human papillomavirus 16 among Australian women with high-grade cervical intraepithelial neoplasia. Int J Gynecol Cancer. 2006 May-Jun;16(3):1032-5. doi: 10.1111/j.1525-1438.2006.00587.x.

  PMID: 16803481 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

We will be collecting blood from the participants, which include the plasma and peripheral blood mononuclear cells.

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Condylomata Acuminata

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; Papillomavirus Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Warts; Skin Diseases, Viral; Tumor Virus Infections; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Edward K Mulholland

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2014
• First Posted: October 28, 2014
• Study Start: February 1, 2015
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: September 23, 2015

Record last verified: 2015-09

Locations

FI (1)