Association between Toll-like receptor and tumor necrosis factor immunological pathways in uterine cervical neoplasms.

ABSTRACT

INTRODUCTION: The immune system plays a critical role in the defense against human papillomavirus (HPV) infection and its persistence. Toll-like receptors (TLRs) are membrane receptors responsible for activation of the innate immune response, and an association between TLR expression and uterine cervical cancer has been shown. Tumor necrosis factors (TNFs) are among the main mediators of skin and mucosa inflammation. The aim of this study was to demonstrate the association between TLR and TNF immune expression and cervical cancer and premalignant cervical lesions. METHODS: A total of 64 embedded tissues were obtained from gynecological procedures, including 35 specimens with cervical intraepithelial neoplasia (CIN) and 10 specimens with cervical squamous cell carcinoma (CSCC) as well as 19 normal cervical samples. The expression of TLR2, TLR3, TLR4, TNF-α and TNF-ß was measured by immunohistochemistry and graded into low and high levels of expression. RESULTS: There was an association between the expression levels of TLR2 and those of TNF-α and TNF-ß (p = 0.01 and p = 0.021, respectively) in the cervical cancer and CIN groups. TLR4 expression was associated with TNF-α and TNF-ß expression (p = 0.016 and p = 0.025, respectively) in these 2 groups. By contrast, TLR3 was not statistically associated with TNF-α or TNF-ß in any of the groups. CONCLUSIONS: There might be an association of the TLR2 and TLR4 pathways with the immunological response of TNF-α and TNF-ß in cervical cancer. These markers are also expressed at higher levels in cervical cancer and premalignant lesions compared to normal controls.