We found that the upregulation expression of TIGIT, KLRG1 on CD56brightNK cells and its ligands Poliovirus receptor (PVR), E-Cadherin, N-Cadherin is directly associated with HPV16(+) CIN, suggesting that NK cell surface inhibitory receptors may be the key components responsible for the compromised viral clearance due to impaired immunity in HPV16(+) subjects with CIN. This evidence concerns the gene CDH2 and cervical squamous intraepithelial neoplasia.