Stephen J.LurieMD, PhD, Senior EditorIndividualAuthorJody W.ZylkeMD, Contributing EditorIndividualAuthor
To the Editor: Dr Anttila and colleagues1 reported that C trachomatis antibodies are associated with a 2.5-fold increased risk of invasive cervical SCC after adjustment for serum antibodies to HPV types 16, 18, and 33.
While advantages of this study include its nested case-control design and the use of the microimmunofluorescence (MIF) assay for ascertainment of past C trachomatis infection, we are concerned that the study does not adequately control for the strong effect of HPV infection. Oncogenic HPV types are the central, and probably necessary, cause of invasive cervical cancer.2 Cofactors may act by increasing susceptibility to HPV infection or by inducing progression from HPV infection to invasive cancer. The current approach to assessing the role of cofactors for progression is restriction of analyses to HPV-positive women. By simply adjusting for HPV seropositivity, residual HPV confounding is expected because HPV serology is less sensitive than the detection of HPV DNA using current criterion standard assays based on the polymerase chain reaction.3 Given the high prevalence of HPV DNA in invasive carcinoma worldwide (>99%),2 misclassification of HPV among cases must have occurred, as only 37% of SCC cases were seropositive for HPV type 16,18, or 33. Further evidence for residual confounding is that the associations between C trachomatis seropositivity and cervical SCC in Table 1 are little modified following adjustment for HPV seropositivity.
Smith JS, Muñoz N, Franceschi S, Eluf-Neto J, Herrero R, Peeling RW. Chlamydia trachomatis and Cervical Squamous Cell Carcinoma. JAMA. 2001;285(13):1703-1706. doi:10.1001/jama.285.13.1703