title: Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Health Sciences, University of Tampere, Tampere 33014, Finland. llmale@uta.fi
authors.forename: Matti
authors.initials: M
authors.lastname: Lehtinen
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Ault
authors.forename: Erika
authors.initials: E
authors.lastname: Lyytikainen
authors.forename: Joakim
authors.initials: J
authors.lastname: Dillner
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Garland
authors.forename: Daron G
authors.initials: DG
authors.lastname: Ferris
authors.forename: Laura A
authors.initials: LA
authors.lastname: Koutsky
authors.forename: Heather L
authors.initials: HL
authors.lastname: Sings
authors.forename: Shuang
authors.initials: S
authors.lastname: Lu
authors.forename: Richard M
authors.initials: RM
authors.lastname: Haupt
authors.forename: Jorma
authors.initials: J
authors.lastname: Paavonen
mesh_terms: D000293:Adolescent; D000328:Adult; D002690:Chlamydia Infections / Q000150:complications* / Q000175:diagnosis; D003075:Coitus; D004279:DNA, Viral; D018450:Disease Progression; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications* / Q000175:diagnosis; D012307:Risk Factors; D012747:Sexual Partners; D002578:Uterine Cervical Dysplasia / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000821:virology*; D055815:Young Adult
chemical_list: D004279:DNA, Viral