Toll‐like receptors: Important immune checkpoints in the regression of cervical intra‐epithelial neoplasia 2. Issue 11 (9th October 2018)

• Record Type: Journal Article
• Authors: Halec, Gordana; Scott, Mark E.; Farhat, Sepideh; Darragh, Teresa M.; Moscicki, Anna‐Barbara
• Is Part Of: International journal of cancer. Volume 143:Issue 11(2018)
• Page Start: 2884
• Page End: 2891
• Publication Date: 2018-10-09
• Subjects: Toll‐like receptors -- human papillomavirus -- cervical intra‐epithelial neoplasia 2 -- CIN2 regression; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31814
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Toll‐like receptors (TLRs) are innate immune defenders thought to be critical for the clearance of human papillomavirus (HPV) infections hence preventing the development of HPV‐associated high‐grade cervical intra‐epithelial neoplasia (CIN2 or 3), a potential cervical cancer precursor. However, the role of TLRs in the regression of established cervical lesions, such as CIN2, is hindered by a lack of prospective design studies. Using SYBR green real‐time PCR assays, we have examined the gene expression of TLR2, TLR3, TLR7, TLR8 and TLR9, in cytobrush collected endocervical cells of 63 women diagnosed with CIN2 at study entry (baseline) and followed over a 3‐year period. Wilcoxon rank‐sum test was used to examine the association between TLR expression levels, measured at baseline, and CIN2 outcome (regression vs . persistence/progression) over time. HPV genotyping was performed using Roche Linear Array Assay detecting 37 HPV types. Women with CIN2 regression showed significantly higher baseline levels of TLR2 ( p = 0.006) and TLR7 ( p = 0.007), as well as a non‐significant trend for a higher TLR8 expression ( p = 0.053) compared to women with CIN2 persistence/progression. Six women with CIN2 regression, who presented with an HR‐HPV DNA‐negative CIN2 lesion at study entry, had significantly higher baseline levels of TLR2 ( p = 0.005), TLR7 ( p = 0.013) and TLR8 ( p = 0.012), compared to women with CIN2 persistence/progression, suggesting their role in clearance of HPV prior to clearance of the lesion. Our results confirm a key role of TLRs in regression of CIN2 and support the potential use of TLR‐agonists for treatment of these lesions. Abstract : What's new? Established cervical cancer precursors such as CIN2 have a regression rate of up to 70%. However, the immune mechanisms by which such Human Papillomavirus (HPV)‐associated pre‐cancers resolve remain unclear. This study found high levels of viral protein‐sensing toll‐like receptors (TLR)2, and viral nucleic acid‐sensing TLR7 and TLR8, at CIN2 diagnosis to be associated with CIN2 regression. Highest levels of TLRs were observed in cervical mucosa of women whose CIN2 lesions did not contain measurable high‐risk HPV infection. These results confirm a key role of TLRs in CIN2 regression and support the potential use of TLR‐agonists for treatment of CIN2 lesions.