Vaginal intraepithelial neoplasia: methodologic problems in a case-control study

Vaginal Intraepithelial Neoplasia (VAIN) has recently received increased attention as a precursor to vaginal cancer, yet its natural history remains largely obscure. Several case series have implicated hysterectomy as a risk factor for the subsequent development of vaginal neoplasia. A recent case-control study failed to support an association with vaginal cancer when controlling for age, sex, and prior cervical dysplasia or neoplasia. In order to further investigate the possible association of hysterectomy with vaginal neoplasia, we performed the following retrospective case-control study. We compared 39 cases of VAIN with 39 controls matched for age, race, and prior cervical dysplasia or neoplasia. Matched-pair analysis yielded an odds ratio of 7.0 with a 95% confidence interval of 1.7 to 28. This would suggest that previous hysterectomy is indeed associated with the development of VAIN. However, several potential sources of systematic error were identified in the study design. Thus this association can not be supported. Further, this study exemplifies the difficulty of generalizing study results from a tertiary care population to primary care settings.