METHODS: Two hundred and forty-two subjects with equivocal papanicolaou smear (Pap smear) results were recruited in this hospital-based and case-controlled study. The residual cervical cells in liquid-based cytological test (LBC) containers were used for genomic DNA extraction and then for ZNF582 (m) and HPV-HR detection. The level of ZNF582 (m) was quantified by real-time methylation-specific PCR after bisulfite conversion. The HPV-HR test was performed by using a nested multiplex PCR (NMPCR) assay that combines degenerate E6/E7 consensus primers and HPV type-specific primers.
RESULTS: Significant associations were observed between ZNF582 (m) and the risk of cervical intraepithelial neoplasia grade 3 or higher (CIN3+; odds ratio = 15.52, 95% confidence interval (CI): 7.73 to 31.18). The sensitivity and specificity of ZNF582 (m) for women with CIN3+ were 82.43% and 76.79%, respectively. High sensitivity (99.33%) but low specificity (38.76%) was observed for HPV-HR. When combining both positive results of ZNF582 (m) and HPV-HR, the sensitivity and specificity were 82.43% and 81.55%, respectively. The sensitivity and specificity of ZNF582 (m) or HPV-16/18 were 89.19% and 70.24%, respectively. However, the sensitivity and specificity of ZNF582 (m) combined with HPV-16/18 (both ZNF582 (m) and HPV-16/18 positive results) were 59.46% and 94.64%, respectively.
CONCLUSIONS: ZNF582 (m) provides a promising triage tool for women with ASC. To effectively manage ASC patients, a new strategy co-testing for ZNF582 (m) and HPV-16/18 genotyping was proposed. This strategy could reduce the number of patients referred for colposcopic examination and thus provide a feasible follow-up solution in the regions where colposcopy is not readily available. This strategy could also prevent women from experiencing unnecessary anxiety caused by HPV-HR.