Significance of ZNF772 methylation and HR-HPV detection in shunt of patients with atypical squamous cell of unknown significance

Objective To explore the significance of zinc finger protein (ZNF) 772 methylation and high-risk human papillomavirus (HR-HPV) detection in the shunt of patients with atypical squamous cell of unknown significance (ASCUS).

Methods A total of 195 initially screened ASCUS patients were selected, all of whom underwent HC2-HPV-DNA testing and ZNF772 gene DNA methylation testing.The differences in ZNF772 gene site methylation levels between patients with cervical intraepithelial neoplasia (CIN) Ⅱ and above and those with CIN Ⅱ and below, CIN Ⅲ and above and CIN Ⅲ and below were compared, and the ZNF772 methylation level and HR-HPV shunt value for ASCUS patients with CIN Ⅱ and above and CIN Ⅲ and above were evaluated.

Results Pathological examination showed that among 195 ASCUS patients, there were 80 cases of inflammation (41.03%), 64 cases of CIN Ⅰ (32.82%), 29 cases of CIN Ⅱ (14.87%), 18 cases of CIN Ⅲ/CIS/AIS (9.23%), and 4 cases of SCC/AC (2.05%).One hundred and forty-one cases (72.31%) were positive for HR-HPV (HC2), and 54 cases (27.69%) were negative for HR-HPV (HC2);The positive detection rate of HR-HPV (HC2) in patients with CIN Ⅱ and above was higher than that in patients with CIN Ⅱ and below (P < 0.05).The positive detection rate of HR-HPV (HC2) in patients with CIN Ⅲ and above is higher than that in patients with CIN Ⅲ and below (P < 0.05).The methylation levels at the -420 and -422 loci of the ZNF772 gene in patients with CIN Ⅱ and above and CIN Ⅲ and above were higher than those in patients with CIN Ⅱ and below (P < 0.05).The methylation levels at the -420 and -422 loci of the ZNF772 gene and the AUC (95%CI) for HR-HPV diagnosis of CIN Ⅱ and above were 0.867 (0.811-0.911), 0.806 (0.743-0.859), and 0.777 (0.712-0.834), respectively. The AUC (95%CI) for diagnosis of CIN Ⅲ and above were 0.891 (0.838-0.931), 0.868 (0.813-0.912), and 0.780 (0.716-0.836), respectively.The highest AUC area was detected for CIN Ⅱ and above, as well as CIN Ⅲ and above, based on the methylation level at the -420 locus of the ZNF772 gene.

Conclusions Compared with HC2-HPV-DNA detection, ZNF772 methylation detection can more accurately identify patients with CIN Ⅱ and above and CIN Ⅲ and above lesions in ASCUS, and is expected to become an effective alternative to shunt ASCUS.