Methylated ZNF582 as a triage marker for occult cervical cancer and advanced cervical intraepithelial neoplasia

Future Oncol. 2022 Jul;18(23):2583-2592. doi: 10.2217/fon-2021-1625. Epub 2022 Jun 27.

Abstract

Aim: To explore the appropriate triage methods for women infected with high-risk human papillomavirus (hrHPV). Materials & methods: A total of 424 out of 872 hrHPV-infected women were divided into cervicitis (n = 123), cervical intraepithelial neoplasia grade 1 (CIN1; n = 89), CIN2 (n = 72), CIN3 (n = 87) and cervical cancer (n = 53) groups. Results: The sensitivity/specificity of ZNF582m, PAX1m and liquid-based cytology (LBC) for hrHPV-infected women with transformation zone 3 CIN3+ was 83.9/93.1, 77.4/90.6 and 80.6/58.5%, respectively. The ZNF582m/PAX1m test had a higher specificity than LBC (p < 0.001) and similar sensitivity to that observed for LBC (p > 0.05). ZNF582m/PAX1m improved the positive predictive value of CIN3+ (64.7/60.0%) in low-grade LBC (negative predictive value: 91.7/88.7%). Conclusion: ZNF582m was superior to PAX1m and LBC tests in detecting CIN3+ in hrHPV-infected women.

Keywords: HPV; PAX1; ZNF582; liquid-based cytology; methylation; transformation zone; triage.

Plain language summary

Human papillomavirus (HPV) testing is the main method for cervical cancer screening. Although most HPV infections are transient and can be cleared by the body, persistent infection with HPV can lead to cervical cancer. In this study, 424 HPV-infected women were divided into normal, cervical intraepithelial neoplasia grade 1 (CIN1), CIN2, CIN3 and cervical cancer groups according to the grade of cervical lesion (low to high). Women with CIN3 or cervical cancer need treatment. ZNF582m, PAX1m and liquid-based cytology detected 83.9, 77.4 and 80.6% of women with CIN3+ and 93.1, 90.6 and 58.5% of women without CIN3+. However, the ZNF582m test was superior to the PAX1m and liquid-based cytology tests.

MeSH terms

  • Early Detection of Cancer / methods
  • Female
  • Humans
  • Kruppel-Like Transcription Factors
  • Neoplasms, Unknown Primary*
  • Papillomavirus Infections* / complications
  • Papillomavirus Infections* / diagnosis
  • Papillomavirus Infections* / genetics
  • Triage
  • Uterine Cervical Dysplasia* / diagnosis
  • Uterine Cervical Dysplasia* / genetics
  • Uterine Cervical Neoplasms* / diagnosis
  • Uterine Cervical Neoplasms* / genetics
  • Vaginal Smears / methods

Substances

  • Kruppel-Like Transcription Factors
  • ZNF582 protein, human