Stephen J.LurieMD, PhD, Senior EditorIndividualAuthorJody W.ZylkeMD, Contributing EditorIndividualAuthor
In Reply: The letters from Ms Gravitt and Dr Castle, and from Dr Smith and colleagues, question our finding of an association between C trachomatis infection and cervical SCC. They claim that the relatively low sensitivity of HPV serology leads to significant nondifferential misclassification bias that makes it difficult to control for residual confounding by HPV by simply adjusting for HPV seropositivity. However, it is inappropriate to compare the results of cross-sectional studies (which generally show a 99% positivity rate for HPV DNA among SCC cases) and longitudinal studies (which have found a 37% positivity rate for serum antibodies to HPV 16, 18, or 33 among women who will subsequently develop SCC). In most cases, HPV infection is usually transient. Therefore, HPV DNA positivity simply reflects the point prevalence of HPV infection, whereas HPV seropositivity is a more stable marker of past exposure to HPV. Also, recent sexual activity could increase the HPV DNA positivity among control subjects but not among those already exposed to HPV, and this could lead to significant systematic bias and hence underestimate the role of sexually transmitted cofactors. Furthermore, the association between C trachomatis and cervical carcinoma was specific for SCC but not for cervical adenocarcinoma or other noncervical anogenital carcinomas.1 Only a longitudinal approach can assess temporal association, which is critical and probably different for different microorganisms or carcinogens in general.
Anttila T, Koskela P, Lehtimen M, Dillner J, Paavonen J. Chlamydia trachomatis and Cervical Squamous Cell Carcinoma—Reply. JAMA. 2001;285(13):1703–1706. doi:10.1001/jama.285.13.1703
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