Diminished IFN-g and IL-10 and elevated Foxp3 mRNA expression in the cervix are associated with CIN 2 or 3

• Published in: International journal of cancer 2009-03, Vol.124 (6), p.1379-1383
• Main Authors: Scott, Mark E, Ma, Yifei, Kuzmich, Lili, Moscicki, Anna-Barbara
• Format: Article
• Language: English
• Subjects: Human papillomavirus; Human papillomavirus 16
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.24117

Cervical mucosal expression of cytokines involved in mediating cellular immunity is believed to influence the persistence of human papillomavirus (HPV) infection, a necessary prerequisite for the development of cervical intraepithelial neoplasia (CIN). Additionally, regulatory T (Treg) cells are increasingly understood to be important modulators of cellular immunity. Using quantitative RT-PCR, we measured, in cross-sectional design, the cervical mRNA expression of IFN-, IL-10, and IL-12, as well as the Treg transcription factor Forkhead box P3 (Foxp3), in a cohort of young women representing CIN 1, 2, and 3, as well as benign histology. Higher levels of IFN- and IL-10 were significantly (p 0.05) associated with decreased odds of having high-grade cervical disease (CIN 2 or 3) in multivariate logistic regression models. In contrast, higher levels of mucosal Foxp3 expression were associated with increased odds of having CIN 2 or 3 (p = 0.004). In a multivariate model including cervical infection with HPV16 and/or another high-risk HPV type, Foxp3 remained higher in the CIN 2/3 group, but the difference was notably less significant (p = 0.05). These findings support a model in which diminished cellular immunity in the cervical mucosa and mucosal enrichment of Treg cells both contribute to the development of high-grade lesions.