Th1 Cytokine Patterns in Cervical Human Papillomavirus Infection

The host's immune response to cervical human papillomavirus (HPV) infection is poorly understood. In a longitudinal cohort of women with cervical HPV infections, defined by PCR-based HPV DNA testing, we used exfoliated cervical cells and reverse transcription-PCR to examine the cervical mucosal mRNA expression of cytokines involved in regulating cell-mediated immunity. We identified seven HPV-positive subjects who were found to have cleared their HPV infections 4 months later. In all seven, a T-helper type 1 (Th1) cytokine pattern (expression of gamma interferon and absence of interleukin-4) preceded clearance. The more variable cytokine patterns seen in HPV-negative subjects suggest that the Th1 pattern in the women with subsequent clearance was a response to the HPV infection. This contention is supported by additional cross-sectional data showing a Th1 pattern in a majority of HPV-positive women. This study establishes a feasible means for assessing local cytokine expression in the cervical milieu and demonstrates that a Th1 cytokine response is associated with subsequent clearance of cervical HPV infection.