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Tarja Anttila, MD; Pekka Saikku, MD; Pentti Koskela, PhD; Aini Bloigu, BSc; Joakim Dillner, MD; Irma Ikäheimo, PhD; Egil Jellum, PhD; Matti Lehtinen, MD; Per Lenner, MD; Timo Hakulinen, PhD; Ale Närvänen, PhD; Eero Pukkala, PhD; Steinar Thoresen, MD; Linda Youngman, PhD; Jorma Paavonen, MD

JAMA. 2001;285:47-51.

Context  Human papillomavirus (HPV) infection has been established as a cause of cervical cancer. Epidemiologic studies suggest that Chlamydia trachomatis infection also confers increased risk for cervical squamous cell carcinoma (SCC). Whether this risk is serotype-specific is unknown.

Objective  To study the association between exposure to different C trachomatis serotypes and subsequent development of cervical SCC.

Design and Setting  Longitudinal, nested case-control study within a cohort of 530 000 women who provided samples to serum banks in Finland, Norway, and Sweden. The data files were linked to respective national cancer registries.

Subjects  One hundred twenty-eight women who had developed invasive cervical SCC at least 12 months following serum donation. Each case had 3 matched controls.

Main Outcome Measure  Risk for the development of cervical SCC by IgG antibodies to 10 different C trachomatis serotypes, adjusted for antibodies to HPV types 16, 18, and 33 and for serum cotinine levels.

Results  Of specific C trachomatis serotypes, serotype G was most strongly associated with SCC (adjusted odds ratio [OR], 6.6; 95% confidence interval [CI], 1.6-27.0). Other serotypes associated with SCC were I (OR, 3.8; 95% CI, 1.3-11.0) and D (OR, 2.7; 95% CI, 1.3-5.6). Presence of serum IgG antibodies to more than 1 serotype increased the adjusted ORs for SCC (P<.001 for trend).

Conclusions  Chlamydia trachomatis serotype G is most strongly associated with subsequent development of cervical SCC. Increasing numbers of exposures to different C trachomatis serotypes also increases risk. Our results strengthen the evidence that there is a link between past C trachomatis infection and cervical SCC.

Author Affiliations: National Public Health Institute, Oulu, Finland (Drs Anttila and Koskela and Ms Bloigu); Department of Medical Microbiology, University of Oulu, Oulu, Finland (Dr Saikku); Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden (Dr Dillner); Microbiology Laboratory, Oulu University Hospital, Oulu, Finland (Dr Ikäheimo); Institute of Clinical Biochemistry, Rikshospitalet, Oslo, Norway (Dr Jellum); School of Public Health, University of Tampere, Tampere, Finland (Dr Lehtinen); Department of Oncology, University of Umeå, Umeå, Sweden (Dr Lenner); Departments of Public Health (Dr Hakulinen) and Obstetrics and Gynecology (Dr Paavonen), University of Helsinki, Helsinki, Finland; Department of Biochemistry, University of Kuopio, Kuopio, Finland (Dr Närvänen); Finnish Cancer Registry, Helsinki (Dr Pukkala); The Cancer Registry of Norway, Oslo (Dr Thoresen); and Clinical Trial Service Unit, University of Oxford, Oxford, England (Dr Youngman).

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