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Primary cervical screening with high risk human papillomavirus testing: observational study

BMJ 2019; 364 doi: (Published 06 February 2019) Cite this as: BMJ 2019;364:l240
  1. Matejka Rebolj, senior epidemiologist12,
  2. Janet Rimmer, senior implementation lead3,
  3. Karin Denton, regional head of quality assurance45,
  4. John Tidy, professor6,
  5. Christopher Mathews, senior data manager12,
  6. Kay Ellis, consultant biomedical scientist7,
  7. John Smith, consultant gynaecological histopathologist and cytopathologist7,
  8. Chris Evans, consultant biomedical scientist8,
  9. Thomas Giles, consultant cytopathologist8,
  10. Viki Frew, consultant biomedical scientist9,
  11. Xenia Tyler, consultant cellular pathologist9,
  12. Alexandra Sargent, clinical scientist10,
  13. Janet Parker, consultant biomedical scientist11,
  14. Miles Holbrook, consultant cytopathologist11,
  15. Katherine Hunt, lead biomedical scientist cytology5,
  16. Penny Tidbury, consultant cellular pathologist5,
  17. Tanya Levine, consultant histopathologist and cytopathologist12,
  18. David Smith, laboratory head of department12,
  19. Julietta Patnick, visiting professor13,
  20. Ruth Stubbs, national cervical screening programme manager3,
  21. Sue Moss, professor1,
  22. Henry Kitchener, professor emeritus14
  1. 1Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  2. 2School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King’s College London, London SE1 9RT, UK
  3. 3Young Person and Adult Screening Programmes, Public Health England, Sheffield, UK
  4. 4PHE Screening Quality Assurance Service South, Public Health England, Bristol, UK
  5. 5Severn Pathology, Southmead Hospital, North Bristol NHS Trust, Bristol, UK
  6. 6Department of Gynaecological Oncology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
  7. 7Cytology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
  8. 8NHS Liverpool Clinical Laboratories, Royal Liverpool University Hospital, Liverpool, UK
  9. 9Department of Cellular Pathology, Norfolk & Norwich University Hospitals NHS Foundation Trust, Norwich, UK
  10. 10Clinical Virology, Manchester University NHS Foundation Trust, Manchester, UK
  11. 11Cellular Pathology, Manchester University NHS Foundation Trust, Manchester, UK
  12. 12Department of Cellular Pathology, Northwick Park Hospital, London, UK
  13. 13Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  14. 14Division of Cancer Sciences, University of Manchester and Manchester NIHR BRC, Manchester, UK
  1. Correspondence to: M Rebolj matejka.rebolj{at}
  • Accepted 1 January 2019


Objective To provide the first report on the main outcomes from the prevalence and incidence rounds of a large pilot of routine primary high risk human papillomavirus (hrHPV) testing in England, compared with contemporaneous primary liquid based cytology screening.

Design Observational study.

Setting The English Cervical Screening Programme.

Participants 578 547 women undergoing cervical screening in primary care between May 2013 and December 2014, with follow-up until May 2017; 183 970 (32%) were screened with hrHPV testing.

Interventions Routine cervical screening with hrHPV testing with liquid based cytology triage and two early recalls for women who were hrHPV positive and cytology negative, following the national screening age and interval recommendations.

Main outcome measures Frequency of referral for a colposcopy; adherence to early recall; and relative detection of cervical intraepithelial neoplasia grade 2 or worse from hrHPV testing compared with liquid based cytology in two consecutive screening rounds.

Results Baseline hrHPV testing and early recall required approximately 80% more colposcopies, (adjusted odds ratio 1.77, 95% confidence interval 1.73 to 1.82), but detected substantially more cervical intraepithelial neoplasia than liquid based cytology (1.49 for cervical intraepithelial neoplasia grade 2 or worse, 1.43 to 1.55; 1.44 for cervical intraepithelial neoplasia grade 3 or worse, 1.36 to 1.51) and for cervical cancer (1.27, 0.99 to 1.63). Attendance at early recall and colposcopy referral were 80% and 95%, respectively. At the incidence screen, the 33 506 women screened with hrHPV testing had substantially less cervical intraepithelial neoplasia grade 3 or worse than the 77 017 women screened with liquid based cytology (0.14, 0.09 to 0.23).

Conclusions In England, routine primary hrHPV screening increased the detection of cervical intraepithelial neoplasia grade 3 or worse and cervical cancer by approximately 40% and 30%, respectively, compared with liquid based cytology. The very low incidence of cervical intraepithelial neoplasia grade 3 or worse after three years supports extending the screening interval.


  • Contributors: JR, KD, JT, KE, JS, TG, VF, XT, AS, MH, PT, TL, JuP, RS, SM, and HK designed the study and had clinical oversight. KE, JS, CE, TG, VF, XT, JaP, KH, TL, and DS acquired the data. MR, CM, and SM performed the analysis. MR and HK drafted the manuscript. All authors provided critical comment. MR and HK submitted the monograph. The members of the participating laboratories were responsible for retrieving the data and transferring it to Queen Mary University of London and can take full responsibility for the integrity and the accuracy of the data specific to their laboratory. MR and CM had full access to the collated data in the study and can take responsibility for the integrity of the collated data and the accuracy of the data analysis. All authors were provided with all statistical reports and tables and could exercise full access to the collated data at Queen Mary University of London. MR and HK are the guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

  • Funding: This work was supported by Public Health England (salary and laboratory activity) and Cancer Research UK (grant C8162/A16892). Public Health England had a role in designing the pilot, in the collection of the data, and commented on the manuscript.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: MR, CM, and SM received financing from Public Health England (PHE) for the epidemiological evaluation. MR attended meetings with various HPV assay manufacturers and received a fee for lecture from Hologic paid to employer. JR, KD, and RS were or are employed by PHE. JT received fees for lectures from Roche, Qiagen, and Hologic; conference registration, accommodation and travel from Sanofi Pasteur; consultancy fees and shareholder in Zilico; patent for electrical impedance spectroscopy in detection of cervical intraepithelial neoplasia with Zilico. KE received fees for lectures from Beckton Dickinson and Roche and conference accommodation and travel from Hologic, Abbott, Becton Dickinson, and Roche. JS received personal speaker bureau fees from Beckton Dickinson and personal medical advisory board fees from Zilico. KD, KE, CE, TG, VF, XT, AS, JP, MH, KH, PT, TL, and DS received funding from PHE to support the NHS screening laboratory activity for the pilot. VF is employed by Norfolk and Norwich University Hospitals NHS Foundation Trust and received the speaker fees from Roche for conferences and travel and accommodation from Roche and Hologic for training and user group meetings. AS received speaker fees from Roche, travel and accommodation from Roche for training, travel and accommodation from Abbott for a user group meeting, attended meetings with HPV assay manufacturers, and received kits for assay validation from Roche, Abbott, Hologic, Becton Dickinson, and Cepheid. HK is the Chair of the Advisory Committee for Cervical Screening (PHE), but the views expressed in this manuscript are those of the author and do not represent the view of PHE. There are no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Women participating in the HPV Primary screening pilots were invited to make an informed choice on participating in the cervical screening programme. A decision is made to accept or decline a screening test based on access to accurate and up-to-date information on the condition being screened for, the testing process and potential outcomes. Specific information was provided at the invitation stage allowing for personalised informed choice. There was further opportunity to reflect on what the test and its results might mean when they attended for screening with the clinician taking the sample. Regulation 5, Health Service Regulations 2002, Confidentiality Advisory Group Reference: 15/CAG/0207, was the legal basis to process the data.

  • Data sharing: No additional data are available.

  • The manuscript’s guarantors (MR and HK) affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned have been explained.

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