The performance of JAM3/PAX1 methylation in the diagnosis of high-grade squamous intraepithelial lesions for women with high-risk HPV infection

BMC Cancer. 2024 Dec 18;24(1):1514. doi: 10.1186/s12885-024-13299-y.

Abstract

Objective: To assess the clinical value of DNA methylation measurement in exfoliated cervical cells for distinguishing high-grade squamous intraepithelial lesions (HSIL) from other cervical abnormalities.

Methods: A total of 276 patients were enrolled, and general clinical information was collected. Exfoliated cervical cells were obtained to assess human papillomavirus (HPV) infection, conduct ThinPrep cytology tests (TCT), and measure methylation levels of JAM3 (△CtJ) and PAX1 (△CtP). Logistic regression was performed to identify factors significantly associated with HSIL diagnosis. A conditional inference tree model and the area under the curve (AUC) were employed to evaluate the efficacy of JAM3 and PAX1 methylation in detecting HSIL.

Results: Independent risk factors for HSIL diagnosis included △CtJ, △CtP, atypical squamous cells of undetermined significance (ASCUS), and HPV16 infection. The conditional inference tree indicated that 96.4% of patients were non-HSIL when △CtJ > 11.66, and 99.1% were non-HSIL when △CtP > 10.97. The diagnostic performance of △CtJ/△CtP surpassed that of TCT/HPV alone. Among six methods, the combination of △CtP, TCT, and high-risk HPV (hr-HPV) testing achieved the highest sensitivity (91.2%), positive predictive value (50.0%), negative predictive value (98.6%), and AUC (0.932).

Conclusion: In women with hr-HPV infection, DNA methylation analysis of cervical cytology outperformed traditional TCT or HPV testing. The combination of △CtP with TCT and HPV may offer the most accurate screening approach for HSIL.

Keywords: JAM3; PAX1; DNA methylation; High-grade squamous intraepithelial lesions; Hr-HPV.

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • DNA Methylation*
  • Female
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / isolation & purification
  • Humans
  • Middle Aged
  • Paired Box Transcription Factors* / genetics
  • Papillomavirus Infections* / diagnosis
  • Papillomavirus Infections* / genetics
  • Papillomavirus Infections* / virology
  • Risk Factors
  • Squamous Intraepithelial Lesions / diagnosis
  • Squamous Intraepithelial Lesions / genetics
  • Squamous Intraepithelial Lesions / pathology
  • Squamous Intraepithelial Lesions / virology
  • Squamous Intraepithelial Lesions of the Cervix / diagnosis
  • Squamous Intraepithelial Lesions of the Cervix / genetics
  • Squamous Intraepithelial Lesions of the Cervix / pathology
  • Squamous Intraepithelial Lesions of the Cervix / virology
  • Uterine Cervical Dysplasia / diagnosis
  • Uterine Cervical Dysplasia / genetics
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms* / diagnosis
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / pathology
  • Uterine Cervical Neoplasms* / virology

Substances

  • PAX1 transcription factor
  • JAM3 protein, human
  • Paired Box Transcription Factors
  • Cell Adhesion Molecules
  • Biomarkers, Tumor