Post hoc analysis of the PATRICIA randomized trial of the efficacy of human papillomavirus type 16 (HPV-16)/HPV-18 AS04-adjuvanted vaccine against incident and persistent infection with nonvaccine oncogenic HPV types using an alternative multiplex type-specific PCR assay for HPV DNA.

Abstract

The efficacy of the human papillomavirus type 16 (HPV-16)/HPV-18 AS04-adjuvanted vaccine against cervical infections with HPV in the Papilloma Trial against Cancer in Young Adults (PATRICIA) was evaluated using a combination of the broad-spectrum L1-based SPF10 PCR-DNA enzyme immunoassay (DEIA)/line probe assay (LiPA25) system with type-specific PCRs for HPV-16 and -18. Broad-spectrum PCR assays may underestimate the presence of HPV genotypes present at relatively low concentrations in multiple infections, due to competition between genotypes. Therefore, samples were retrospectively reanalyzed using a testing algorithm incorporating the SPF10 PCR-DEIA/LiPA25 plus a novel E6-based multiplex type-specific PCR and reverse hybridization assay (MPTS12 RHA), which permits detection of a panel of nine oncogenic HPV genotypes (types 16, 18, 31, 33, 35, 45, 52, 58, and 59). For the vaccine against HPV types 16 and 18, there was no major impact on estimates of vaccine efficacy (VE) for incident or 6-month or 12-month persistent infections when the MPTS12 RHA was included in the testing algorithm versus estimates with the protocol-specified algorithm. However, the alternative testing algorithm showed greater sensitivity than the protocol-specified algorithm for detection of some nonvaccine oncogenic HPV types. More cases were gained in the control group than in the vaccine group, leading to higher point estimates of VE for 6-month and 12-month persistent infections for the nonvaccine oncogenic types included in the MPTS12 RHA assay (types 31, 33, 35, 45, 52, 58, and 59). This post hoc analysis indicates that the per-protocol testing algorithm used in PATRICIA underestimated the VE against some nonvaccine oncogenic HPV types and that the choice of the HPV DNA testing methodology is important for the evaluation of VE in clinical trials. (This study has been registered at ClinicalTrials.gov under registration no. NCT00122681.).

• Authors: Frank Struyf, Brigitte Colau, Cosette M Wheeler, Paulo Naud, Suzanne Garland, Wim Quint, Song-Nan Chow, Jorge Salmerón, Matti Lehtinen, M Rowena Del Rosario-Raymundo, Jorma Paavonen, Júlio C Teixeira, Maria Julieta Germar, Klaus Peters, S Rachel Skinner, Genara Limson, Xavier Castellsagué, Willy A J Poppe, Brian Ramjattan, Terry D Klein, Tino F Schwarz, Archana Chatterjee, Wiebren A A Tjalma, Francisco Diaz-Mitoma, David J M Lewis, Diane M Harper, Anco Molijn, Leen-Jan van Doorn, Marie-Pierre David, Gary Dubin, HPV PATRICIA Study Group
• Journal: Clinical and vaccine immunology : CVI (Clin Vaccine Immunol) Vol. 22 Issue 2 Pg. 235-44 (Feb 2015) ISSN: 1556-679X [Electronic] United States
• PMID: 25540273 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• ASO4 mixture
• Adjuvants, Immunologic
• DNA, Viral
• Lipid A
• Papillomavirus Vaccines
• human papillomavirus vaccine, L1 type 16, 18
• Aluminum Hydroxide

Topics

• Adjuvants, Immunologic (administration & dosage)
• Adolescent
• Adult
• Aluminum Hydroxide (administration & dosage)
• DNA, Viral (genetics)
• Female
• Genotype
• Humans
• Lipid A (administration & dosage, analogs & derivatives)
• Papillomaviridae (classification, genetics, isolation & purification)
• Papillomavirus Infections (prevention & control, virology)
• Papillomavirus Vaccines (administration & dosage, immunology)
• Polymerase Chain Reaction
• Treatment Outcome
• Young Adult