Efficacy of the HPV-16/18 AS04-adjuvanted Vaccine Against Low-risk HPV Types (PATRICIA Randomized Trial): an Unexpected Observation

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2013 Oct 5

PMID 24092907

Citations 34

Authors

Anne Szarewski

S Rachel Skinner

Suzanne M Garland

Barbara Romanowski

Tino F Schwarz

Dan Apter

Song-Nan Chow

Jorma Paavonen

M Rowena Del Rosario-Raymundo

Julio C Teixeira

Newton S de Carvalho

Maria Castro-Sanchez

Xavier Castellsague

Willy A J Poppe

Philippe De Sutter

Warner Huh

Archana Chatterjee

Wiebren A Tjalma

Ronald T Ackerman

Mark Martens

Kim A Papp

Jose Bajo-Arenas

Diane M Harper

Aureli Torne

Marie-Pierre David

Frank Struyf

Matti Lehtinen

Gary Dubin

Affiliations

Soon will be listed here.

Abstract

Background: Public Health England has reported a decrease of up to 20.8% in new diagnoses of external genital warts (GWs) among women aged <19 years since the national vaccination program with the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine began in 2008. A post hoc analysis of the phase III PATRICIA (PApilloma TRIal against Cancer In young Adults) trial (NCT00122681) was performed to ascertain whether protection against low-risk HPV types was apparent.

Methods: Vaccine efficacy (VE) at 48 months was assessed against 6-month persistent infection (6MPI) with low-risk HPV types in the total vaccinated cohort (TVC) and in the TVC naive (for 25 HPV types tested) populations.

Results: In the TVC naive cohort, VE against 6MPI (95% confidence interval) was 34.5% (11.3 to 51.8) for HPV-6/11, 34.9% (9.1 to 53.7) for HPV-6, 30.3% (-45.0 to 67.5) for HPV-11, and 49.5% (21.0 to 68.3) for HPV-74.

Conclusions: The HPV-16/18 AS04-adjuvanted vaccine appears to have moderate efficacy against persistent infections with a number of low-risk HPV types (HPV-6/11/74), which are responsible for the majority of external GWs, and recently, antibody and cell-mediated immune response to HPV-6/11 have been observed. These findings may help to explain the decrease in external GW diagnoses seen in England.

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References

Paavonen J, Naud P, Salmeron J, Wheeler C, Chow S, Apter D . Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet. 2009; 374(9686):301-14. DOI: 10.1016/S0140-6736(09)61248-4. View

Schiller J, Day P, Kines R . Current understanding of the mechanism of HPV infection. Gynecol Oncol. 2010; 118(1 Suppl):S12-7. PMC: 3493113. DOI: 10.1016/j.ygyno.2010.04.004. View

van Doorn L, Molijn A, Kleter B, Quint W, Colau B . Highly effective detection of human papillomavirus 16 and 18 DNA by a testing algorithm combining broad-spectrum and type-specific PCR. J Clin Microbiol. 2006; 44(9):3292-8. PMC: 1594708. DOI: 10.1128/JCM.00539-06. View

Schiffman M, Herrero R, DeSalle R, Hildesheim A, Wacholder S, Rodriguez A . The carcinogenicity of human papillomavirus types reflects viral evolution. Virology. 2005; 337(1):76-84. DOI: 10.1016/j.virol.2005.04.002. View

Lanitis T, Carroll S, OMahony C, Charman F, Khalid J, Griffiths V . The cost of managing genital warts in the UK. Int J STD AIDS. 2012; 23(3):189-94. DOI: 10.1258/ijsa.2011.011218. View

Howell-Jones R, Soldan K, Wetten S, Mesher D, Williams T, Gill O . Declining genital Warts in young women in england associated with HPV 16/18 vaccination: an ecological study. J Infect Dis. 2013; 208(9):1397-403. PMC: 3789575. DOI: 10.1093/infdis/jit361. View

Petaja T, Keranen H, Karppa T, Kawa A, Lantela S, Siitari-Mattila M . Immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in healthy boys aged 10-18 years. J Adolesc Health. 2008; 44(1):33-40. DOI: 10.1016/j.jadohealth.2008.10.002. View

Wheeler C, Castellsague X, Garland S, Szarewski A, Paavonen J, Naud P . Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2011; 13(1):100-10. DOI: 10.1016/S1470-2045(11)70287-X. View

Einstein M, Baron M, Levin M, Chatterjee A, Fox B, Scholar S . Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine: follow-up from months 12-24 in a Phase III randomized study of healthy women aged 18-45 years. Hum Vaccin. 2011; 7(12):1343-58. PMC: 3338932. DOI: 10.4161/hv.7.12.18281. View

10.

Clifford G, Rana R, Franceschi S, Smith J, Gough G, Pimenta J . Human papillomavirus genotype distribution in low-grade cervical lesions: comparison by geographic region and with cervical cancer. Cancer Epidemiol Biomarkers Prev. 2005; 14(5):1157-64. DOI: 10.1158/1055-9965.EPI-04-0812. View

11.

Pirotta M, Ung L, Stein A, Conway E, Mast T, Fairley C . The psychosocial burden of human papillomavirus related disease and screening interventions. Sex Transm Infect. 2009; 85(7):508-13. DOI: 10.1136/sti.2009.037028. View

12.

Einstein M, Baron M, Levin M, Chatterjee A, Fox B, Scholar S . Comparison of the immunogenicity of the human papillomavirus (HPV)-16/18 vaccine and the HPV-6/11/16/18 vaccine for oncogenic non-vaccine types HPV-31 and HPV-45 in healthy women aged 18-45 years. Hum Vaccin. 2011; 7(12):1359-73. PMC: 3338933. DOI: 10.4161/hv.7.12.18282. View

13.

Lehtinen M, Paavonen J . Sound efficacy of prophylactic HPV vaccination: Basics and implications. Oncoimmunology. 2012; 1(6):995-996. PMC: 3489772. DOI: 10.4161/onci.20011. View

14.

Salisbury D . Male vaccination against human papillomavirus. Lancet Infect Dis. 2012; 12(8):582-3. DOI: 10.1016/S1473-3099(12)70082-8. View

15.

Lehtinen M, Paavonen J, Wheeler C, Jaisamrarn U, Garland S, Castellsague X . Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2011; 13(1):89-99. DOI: 10.1016/S1470-2045(11)70286-8. View

16.

Garland S, Steben M, Sings H, James M, Lu S, Railkar R . Natural history of genital warts: analysis of the placebo arm of 2 randomized phase III trials of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine. J Infect Dis. 2009; 199(6):805-14. DOI: 10.1086/597071. View

17.

Aubin F, Pretet J, Jacquard A, Saunier M, Carcopino X, Jaroud F . Human papillomavirus genotype distribution in external acuminata condylomata: a Large French National Study (EDiTH IV). Clin Infect Dis. 2008; 47(5):610-5. DOI: 10.1086/590560. View