Association of cutaneous anergy with human papillomavirus and cervical neoplasia in HIV-seropositive and seronegative women

Abstract

Cutaneous anergy testing evaluates delayed type hypersensitivity responses and is, in essence, an in-vivo measure of cell-mediated immune function at an epithelial surface. This study assessed the relationship of anergy test results with cervical infection by human papillomavirus (HPV) and cervical neoplasia in HIV-seropositive and seronegative women. HIV-seropositive (n = 1029) and HIV-seronegative (n = 272) women enrolled in a long-term cohort study were followed semi-annually with HPV-DNA testing and cytology. Anergy was defined as unresponsiveness to Candida albicans, tetanus toxoid, and mumps antigen. Anergy was associated with the prevalent detection of squamous intraepithelial lesions [SIL; adjusted odds ratio 1.70; 95% confidence interval (CI) 1.16-2.48] in multivariable logistic regression models, and with the incident detection of oncogenic HPV (adjusted hazard ratio 1.24; 95% CI 0.99-1.56) in multivariable Cox regression models. These models adjusted for HIV infection, combined CD4 T-cell and HIV-RNA strata (13 separate strata to control optimally for their interactive effects), as well as other variables. Cutaneous anergy testing may measure aspects of local cellular immune function in epithelial tissues that are important for the control of HPV and development of SIL, and that in HIV-seropositive women are not fully accounted for by circulating CD4 T-cell counts and HIV-RNA levels.