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. 2024 Jul 29;24(1):913.
doi: 10.1186/s12885-024-12696-7.

Evaluating PAX1 methylation for cervical cancer screening triage in non-16/18 hrHPV-positive women

Meiyuan Huang  1 , Taoli Wang  1 , Ming Li  2 , Mei Qin  3 , Shuang Deng  1 , Dongliang Chen  4
Affiliations

Evaluating PAX1 methylation for cervical cancer screening triage in non-16/18 hrHPV-positive women

Meiyuan Huang et al. BMC Cancer. .

Abstract

Background: In China, the national cervical cancer screening protocol involves initial testing for high-risk human papillomavirus (hrHPV), followed by cytology for hrHPV-positive cases. This study evaluates the effectiveness of PAX1 methylation (PAX1m) analysis in identifying precancerous or cancerous lesions in cervical samples from Chinese women positive for non-16/18 hrHPV strains.

Methods: Between February 2022 and March 2023, 281 cervical samples from non-16/18 hrHPV-positive women underwent cytological examination and PAX1m analysis. The study assessed the statistical relationship between PAX1m levels and the presence of cervical lesions, comparing the diagnostic performance of PAX1m to conventional cytology.

Results: A significant association was found between PAX1 methylation levels and the risk of CIN2 + and CIN3 + lesions, with 47 instances of CIN2 + detected. Odds ratios (ORs) for moderate and high PAX1m levels were 8.86 (95% CI: 2.24-42.17) and 166.32 (95% CI: 47.09-784.97), respectively. The area under the ROC curve for PAX1m in identifying CIN2 + lesions was 0.948 (95% CI: 0.895-0.99). PAX1m demonstrated similar sensitivity and negative predictive value (NPV) to cytology but reduced the colposcopy referral rate from 47.7% with cytology alone to 25.6% with PAX1m, showing superior specificity and positive predictive value across age groups.

Conclusions: PAX1 methylation is a strong indicator of CIN2 + and CIN3 + risk, offering diagnostic performance comparable to cytology with the added benefit of reduced unnecessary colposcopy referrals. These findings support the use of PAX1m analysis as a reliable tool for triaging non-16/18 hrHPV-positive women in outpatient settings.

Keywords: CIN; Cervical cancer; Colposcopy referral; PAX1 methylation; hrHPV.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study flow chart. Abbreviations LEEP, loop electrosurgical excision procedure; CKC, cold knife conization; CIN1, cervical intraepithelial neoplasm grade 1; CIN2, cervical intraepithelial neoplasm grade 2; CIN3, cervical intraepithelial neoplasm grade 3; Ca, cervical cancer
Fig. 2
Fig. 2
PAX1 methylation distribution plots and ROC curves for CIN2+/CIN3 + detection. A, Violin plots of PAX1m (ΔCp) levels grouped according to cytology results. B, Violin plots of PAX1m (ΔCp) levels grouped according to biopsy results. C, ROC curve for the PAX1m-based detection of CIN2 + lesions. D, ROC curve for the PAX1m-based detection of CIN3 + lesions. Abbreviations: NILM, negative for intraepithelial lesions or malignancy; ASC-US, atypical squamous cells of undetermined significance; LSIL, low-grade squamous intraepithelial lesion; ASC-H, atypical squamous cells cannot exclude HSIL; HSIL, high-grade squamous intraepithelial lesion; CIN1, cervical intraepithelial neoplasm grade 1; CIN2, cervical intraepithelial neoplasm grade 2; CIN2+, cervical intraepithelial neoplasm grade 2 or worse; CIN3, cervical intraepithelial neoplasm grade 3; CIN3+, cervical intraepithelial neoplasm grade 3 or worse; Ca, cervical cancer; ROC, receiver operator characteristic curve; AUC, area of under the ROC. Statistical identification: NS., no significance; *, P < 0.05; **, P < 0.01; ***, P < 0.001
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