Background cofactors might affect the risk of the rare progression from infection with carcinogenic human papillomavirus (HPV) to cervical premalignancy to invasive cancer. Some studies have suggested that Chlamydia trachomatis infection is associated with increased risk for cervical cancer. In a large prospective cohort, AECC investigator Burk and his collaborators assessed the role of C trachomatis in cervical premalignancy and addressed confounding by HPV. One hundred and eighty two women with prevalent, and 132 women with incident, histological cervical intraepithelial neoplasia grade 2 (CIN2), grade 3 (CIN3), or cervical cancer (CIN2+) were in the Costa Rica HPV Natural History Study. Nine hundred and ninety nine subjects randomly selected from the same study. The authors found that trachomatis positivity at enrollment was associated with CIN2+ and concurrent and subsequent carcinogenic HPV infection. To account for confounding by HPV status, the analysis was restricted to women positive for carcinogenic HPV DNA at enrollment. No association was found between C trachomatis status at enrollment and combined prevalent and/or incident CIN2+. Hence, no association was found between C trachomatis status, as assessed by DNA or IgG, and risk of cervical premalignancy, after controlling for carcinogenic HPV-positive status. The investigators suggested that previous positive associations between C trachomatis and cervical premalignancy could have been caused, in part, by an increased susceptibility to HPV infection.