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Hypersensitivity reactions to human papillomavirus vaccine in Australian schoolgirls: retrospective cohort study

BMJ 2008; 337 doi: (Published 03 December 2008) Cite this as: BMJ 2008;337:a2642

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  1. Liew Woei Kang, clinical fellow and associate consultant12,
  2. Nigel Crawford, consultant paediatrician34,
  3. Mimi L K Tang, associate professor and director15,
  4. Jim Buttery, infectious disease physician34,
  5. Jenny Royle, consultant paediatrician3,
  6. Michael Gold, senior lecturer and head6,
  7. Christine Ziegler, consultant allergist and immunologist6,
  8. Patrick Quinn, consultant allergist and immunologist6,
  9. Sonja Elia, immunisation nurse consultant3,
  10. Sharon Choo, consultant allergist and immunologist1
  1. 1Department of Allergy and Immunology, Royal Children’s Hospital, Flemington Road, Parkville, Victoria 3052, Australia
  2. 2Paediatric Allergy, Immunology and Rheumatology, Department of Paediatric Medicine, KK Women’s and Children’s Hospital, Singapore
  3. 3Department of General Medicine, Royal Children’s Hospital, Melbourne, Australia
  4. 4NHMRC Centre for Clinical Research Excellence in Child and Adolescent Immunisation, Surveillance of Adverse Events Following Vaccination in the Community, Murdoch Children’s Research Institute, Department of Paediatrics, University of Melbourne, Melbourne, Australia
  5. 5Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, and Department of Paediatrics, University of Melbourne, Australia
  6. 6Department of Allergy and Immunology, Women’s and Children’s Hospital, Adelaide, Australia
  1. Correspondence to: S Choo sharon.choo{at}
  • Accepted 1 October 2008


Objective To describe the outcomes of clinical evaluation, skin testing, and vaccine challenge in adolescent schoolgirls with suspected hypersensitivity to the quadrivalent human papillomavirus vaccine introduced in Australian schools in 2007.

Design Retrospective cohort study.

Setting Two tertiary paediatric allergy centres in Victoria and South Australia, Australia.

Participants 35 schoolgirls aged 12 to 18.9 years with suspected hypersensitivity reactions to the quadrivalent human papillomavirus vaccine.

Main outcome measures Clinical review and skin prick and intradermal testing with the quadrivalent vaccine and subsequent challenge with the vaccine.

Results 35 schoolgirls with suspected hypersensitivity to the quadrivalent human papillomavirus vaccine were notified to the specialised immunisation services in 2007, after more than 380 000 doses had been administered in schools. Of these 35 schoolgirls, 25 agreed to further evaluation. Twenty three (92%) experienced reactions after the first dose. Thirteen (52%) experienced urticaria or angio-oedema, and of these, two experienced anaphylaxis. Thirteen had generalised rash, one with angio-oedema. The median time to reaction was 90 minutes. Nineteen (76%) underwent skin testing with the quadrivalent vaccine: all were skin prick test negative and one was intradermal test positive. Eighteen (72%) were subsequently challenged with the quadrivalent vaccine and three (12%) elected to receive the bivalent vaccine. Seventeen tolerated the challenge and one reported limited urticaria four hours after the vaccine had been administered. Only three of the 25 schoolgirls were found to have probable hypersensitivity to the quadrivalent vaccine.

Conclusion True hypersensitivity to the quadrivalent human papillomavirus vaccine in Australian schoolgirls was uncommon and most tolerated subsequent doses.


  • We thank the allergy and immunology department and immunisation nurse consultants from the Royal Children’s Hospital and the South Australian Immunisation Coordination Unit for their assistance. NC acknowledges support from a National health and Medical Research Council PhD postgraduate public health research scholarship.

  • Contributors: WK, SC, MT, and MG developed the study protocol. WK, NC, CZ, SC, SE, and PQ evaluated the participants. WK collated and analysed the data, WK and SC wrote the draft manuscript. MG, NC, MT, JB, and JR contributed to revisions of the manuscript. All authors gave their approval of this version to be published. SC is the guarantor.

  • Funding: None.

  • Competing interests: MT is chairperson of an incorporated association Asia Pacific Immunoglobulins in Immunology Expert Group that is supported by an unrestricted grant from CSL. JB has served on an advisory board for GSK and serves on a data safety monitoring board for CSL. MCRI receives reimbursement from both GSK and CSL for JB’s attendance at advisory board and scientific meetings.

  • Ethical approval: Not required.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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