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

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

Dan Sun #  1   2 , Changfa Shu #  1 , Fei Zeng  1 , Dabao Xu  3 , Xingping Zhao  4   5   6
Affiliations

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

Dan Sun et al. BMC Cancer. .

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.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki and approved by the ethics committee of the Third Xiangya Hospital of Central South University (No. 23137). All participants provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Heatmap depicting the correlation between different clinical variables. *P < 0.05
Fig. 2
Fig. 2
Predictors for the hierarchical diagnosis of HSIL using conditional inference tree. A △CtJ: (1) ≤ 9.95, 26.9% of patients were non-HSIL; (2) > 9.95 and ≤ 11.66, 75.9% of patients were non-HSIL; (3) > 11.66, 96.4% of patients were non-HSIL. B △CtP: (1) ≤ 6.23, 32.3% of patients were non-HSIL; (2) > 6.23 and ≤ 10.97, 90.6% of patients were non-HSIL; (3) > 10.97, 99.1% of patients were non-HSIL. C △CtJ + TCT + HPV: (1) △CtJ ≤ 9.95, 26.9% of patients were non-HSIL; (2) △CtJ > 9.95 and a TCT result of HSIL: 66.7% of patients were non-HSIL; (3) △CtJ > 9.95 and a TCT result of LSILs/ ASCUS: 97.5% of patients were diagnosed with non-HSIL; (4) △CtJ > 9.95, a TCT result of NILM, and an HPV strain of 18/52/others: all patients were non-HSIL; (5) △CtJ > 9.95, a TCT result of NILM, and an HPV strain of 16/58: 70.6% of patients were non-HSIL. D △CtP + TCT + HPV: (1) △CtP ≤ 6.23, 32.3% of patients were non-HSIL; (2) △CtP > 6.23 and a TCT result of LSILs/ASCUS: 97.9% of patients were non-HSIL; (3) △CtP > 6.23 with a TCT result of HSILs/NILM and an hr-HPV infection of strains 18/52/others: 93.3% of patients were non-HSIL; (4) a TCT result of HSIL/NILM, HPV infection of strains 18/52/others and △CtP > 6.23 but ≤ 10.97: 41.7% of patients were non-HSIL; (5) △CtP > 10.97, a TCT result of HSIL/NILM and hr-HPV infection of strains 18/52/others: all of patients were non-HSIL
Fig. 3
Fig. 3
ROC curve of each clinical index for HSIL diagnosis
See this image and copyright information in PMC

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