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Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia
  1. Matti Lehtinen1,
  2. Kevin A Ault2,
  3. Erika Lyytikainen3,
  4. Joakim Dillner4,5,6,
  5. Suzanne M Garland7,8,
  6. Daron G Ferris9,10,
  7. Laura A Koutsky11,
  8. Heather L Sings12,
  9. Shuang Lu12,
  10. Richard M Haupt12,
  11. Jorma Paavonen13,
  12. for the FUTURE I and II Study Group
  1. 1School of Health Sciences, University of Tampere, Tampere, Finland
  2. 2Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia, USA
  3. 3National Institute for Health & Welfare and Department of Dermatology, University of Oulu, Oulu, Finland
  4. 4Department of Laboratory Medicine, Lund University, Malmö, Sweden
  5. 5Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
  6. 6Department of Medical Epidemiological & Biostatistics, Karolinska Institute, Stockholm, Sweden
  7. 7Microbiology and Infectious Diseases Department, Royal Women's Hospital, Murdoch Children's Research Institute, Australia
  8. 8Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia
  9. 9Department of Family Medicine, Medical College of Georgia, Augusta, Georgia, USA
  10. 10Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta, Georgia, USA
  11. 11Department of Epidemiology, University of Washington, Seattle, Washington, USA
  12. 12Department of Research, Merck Sharp & Dohme, Corp., Whitehouse Station, New Jersey, USA
  13. 13Department of Obstetrics and Gynecology, University of Helsinki, Helsinki, Finland
  1. Correspondence to Matti Lehtinen, School of Health Sciences, University of Tampere, Tampere 33014, Finland; llmale{at}


Objectives High-risk human papillomavirus (hrHPV) is the primary cause of cervical cancer. As Chlamydia trachomatis is also linked to cervical cancer, its role as a potential co-factor in the development of cervical intraepithelial neoplasia (CIN) grade 2 or higher was examined.

Methods The placebo arms of two large, multinational, clinical trials of an HPV6/11/16/18 vaccine were combined. A total of 8441 healthy women aged 15–26 years underwent cervicovaginal cytology (Papanicolaou (Pap) testing) sampling and C trachomatis testing at day 1 and every 12 months thereafter for up to 4 years. Protocol-specified guidelines were used to triage participants with Pap abnormalities to colposcopy and definitive therapy. The main outcome measured was CIN.

Results At baseline, 2629 (31.1%) tested positive for hrHPV DNA and 354 (4.2%) tested positive for C trachomatis. Among those with HPV16/18 infection (n=965; 11.4%) or without HPV16/18 infection (n=7382, 87.5%), the hazard ratios (HRs) associated with development of any CIN grade 2 according to baseline C trachomatis status were 1.82 (95% CI: 1.06 to 3.14) and 1.74 (95% CI 1.05 to 2.90), respectively. The results were comparable when only the 12 most common hrHPV infections were considered, but the excess risk disappeared when the outcome was expanded to include CIN grade 3 or worse.

Conclusion Further studies based on larger cohorts with longitudinal follow-up in relation to the C trachomatis acquisition and a thorough evaluation of temporal relationships of infections with hrHPV types, C trachomatis and cervical neoplasia are needed to demonstrate whether and how in some situations C trachomatis sets the stage for cervical carcinogenesis.

Trial registration NCT00092521 and NCT00092534.

  • Chlamydia trachomatis

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  • Linked article: 049775.

  • Funding This study was funded by Merck Sharp & Dohme, Whitehouse Station, NJ.

  • Competing interests ML, KAA, JD, SMG, DGF and LAK have received funding through their institutions to conduct HPV vaccine studies for Merck. KAA has received consultancy and advisory board fees from Merck, and has received funding through his institution to conduct HPV-related research for Roche, Gen Probe and GlaxoSmithKline. JD has received consultancy fees, lecture fees and research grants from Merck and Sanofi Pasteur MSD. SMG has received advisory board fees and grant support from Commonwealth Serum Laboratories and GlaxoSmithKline, and lecture fees from Merck. DGF has received consultancy fees and funding through his institution to conduct HPV vaccine studies for GlaxoSmithKline, and lecture fees from Merck. JP has received consultancy fees and travel grants from Merck and GlaxoSmithKline. HLS, SL and RMH are employees of Merck and potentially own stock and/or stock options in the company.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the institutional review boards (ethical review committees).

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

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