Triage by PAX1 and ZNF582 Methylation in Women With Cervical Intraepithelial Neoplasia Grade 3: A Multicenter Case–Control Study

Fu, Kun; Lei, Ming; Wu, Lisha; Shi, Junren; Yang, Siyu; Yang, Wenqing; Xu, Jinyun; Kang, Yi Lan; Yang, Zhenying; Zhang, Xuan; Huang, Kangni; Han, Chi Son; Tian, Ye; Zhang, Yu

doi:10.1093/ofid/ofac013

Cited by 6 publications

(4 citation statements)

References 34 publications

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“…In our study, CDB-confirmed CIN2 and CIN3 were stratified to predict pathological progression after CKC. We found that 19.5% (23/118) of the CDB-confirmed CIN3 cases were pathologically upgraded to ESCC after CKC, which was higher than previously reported ( 15 ), indicating that CDB alone is insufficient for the diagnosis of microinvasive cervical cancer ( 21 ). In the CDB-confirmed CIN2 group, 36% of the CIN2 cases were pathologically upgraded to CIN3 and 30% regressed to LSIL and below, however, none of the CIN2 cases were pathologically upgraded to SCC after CKC.…”

Section: Discussioncontrasting

confidence: 59%

“…PAX1 m has also been reported to predict the efficacy of concurrent chemo-radiotherapy in cervical cancer ( 13 ), and is a potential biomarker for monitoring the prognosis of cervical adenocarcinoma ( 14 ). However, few studies have evaluated PAX1 gene methylation before conization, it has been previously reported that PAX1 m would be a suitable alternative method to conventional options and it has the ability to predict the outcome of conization in CIN3 cases ( 15 ). However, the role of PAX1 m in predicting the pathological upgrade of CIN2 is unclear.…”

Section: Introductionmentioning

confidence: 99%

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The role of PAX1 methylation in predicting the pathological upgrade of cervical intraepithelial neoplasia before cold knife conization

Zhao

et al. 2023

Front. Oncol.

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ObjectiveTo explore the ability of PAX1 methylation (PAX1m) to predict the pathological upgrade of cervical intraepithelial neoplasia (CIN) before cold knife conization (CKC).MethodsA total of 218 women that underwent colposcopy-directed biopsy (CDB) pathology for the confirmation of CIN2 and CIN3 between December 2020 to September 2021 were enrolled in this study. The methylation levels of PAX1 (ΔCpPAX1) were determined by quantitative methylation-specific polymerase chain reaction (qMSP). Receiver operating characteristic curve was used to identify the optimal cut-off value of ΔCpPAX1 for predicting the pathological upgrade of disease.ResultsIn the CDB-confirmed CIN2 group, 36% of CIN2 was found to have pathologically upgraded to CIN3 and 30% regressed to low-grade squamous intraepithelial lesion (LSIL) and below, and none of CIN2 upgraded to early-stage cervical cancer (ESCC) after CKC. In the CDB-confirmed CIN3 group, 19.5% (23/118) of CDB-confirmed CIN3 were pathologically upgraded to ESCC after CKC. Regardless of CIN2 or CIN3, the ΔCpPAX1 level of women with upgraded pathology after CKC was significantly lower than that of women with degraded pathology. The optimal △CpPAX1 cut-off value in predicting CIN3 to be upgraded to ESCC after CKC was 6.360 and the area under the curve (AUC) was 0.814, with similar sensitivity (78.3%) and higher specificity (84.2%) than cytology≥LSIL (Se:78.3%;Sp:58.9%) and HPV16/18 positive (Se:73.9%;Sp:46.3%) patients.ConclusionsPAX1m could be a promising auxiliary marker in predicting the pathological upgrade of CIN before CKC. We found that if the △Cp PAX1 cut-off value is lower than 6.360, it is highly suggestive of invasive cervical cancer.

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Section: Discussioncontrasting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

The role of PAX1 methylation in predicting the pathological upgrade of cervical intraepithelial neoplasia before cold knife conization

Zhao

et al. 2023

Front. Oncol.

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“…43,44 No study about HPV methylation and SIR has been reported, while it's noted that LAX1 and ZNF582, the biomarkers of methylation detection, has been reported to be probably correlated with difference of transformation from cervical inflammation to carcinoma. 45,46 Applying p16/ki67 dual staining also showed prognostic value in triaging women with HPV infection associated diseases. 47,48 These findings suggested that combining various HR-HPV infection status tests and SIR biomarkers may contribute to disease surveillance and outcome prediction, and even the triage of clinical populations.…”

Section: Discussionmentioning

confidence: 99%

Platelet-to-Lymphocyte Ratio (PLR) as the Prognostic Factor for Recurrence/Residual Disease in HSIL Patients After LEEP

Huang¹,

Gao²,

Chen³

et al. 2023

JIR

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The platelet-to-lymphocyte ratio (PLR) is considered correlated with cancer prognosis including cervical cancer, in addition to highrisk papillomavirus (HR-HPV) infection, of which the predictive value in prognosis of high-grade squamous intraepithelial lesions (HSILs) remains unknown. Here, the prognostic predictive value of PLR in HSIL after loop electrosurgical excision procedure (LEEP) was evaluated. Patients and Methods: This study included 335 nonpregnant participants with histopathologically confirmed HSIL and 3-and 5-year follow-ups from the Fujian Cervical Lesions Screening Cohorts (FCLSCs) between September 2016 and September 2018. PLR and other variables were evaluated to identify the factors related to the recurrence/residual cervical intraepithelial neoplasia (CIN)-free survival (RFS), namely, the time from LEEP at baseline to first detection of recurrence/residual CIN or end of follow-up, by logistic and Cox regression. Results: In the Kaplan-Meier analysis, HR-HPV infection (p=0.049/0.012), higher PLR (p=0.031/0.038), and gland invasion (p=0.047) had a higher risk for recurrence/residual CIN at the 3-/5-year follow-up. The univariate logistic and Cox regression analyses showed significant differences and a higher cumulative risk in patients with HR-HPV infection (OR=3.917, p=0.026; HR=3.996, p=0.020) and higher PLR (OR=2.295, p=0.041; HR=2.161, p=0.030) at the 5-year follow-up. The findings by multivariate Cox regression analysis were similar, indicating a poor prognosis for patients with HR-HPV infection (HR=3.901, p=0.023) and higher PLR (HR=2.082, p=0.038) at the 5-year follow-up. The calibration plot showed a better model fit for RFS at the 3-year follow-up. Conclusion:Preoperative PLR level and HR-HPV infection could be available markers for predicting recurrence/residual disease of HSIL after LEEP. Clinically, combining PLR with HR-HPV tests may provide novel evaluation method and reference for management in post-treatment patients with cervical precancerous lesions.

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“…However, due to the cost and the limitation of detection method, it is challenging to expand the application of these predictive factors. Numerous studies highlighted that the methylation, especially PAX1 methylation, had high screening accuracy for CIN2 + , serving as a potential triage method for women with HPV infections or as a predictor of the worst pathological outcome [23,[43][44][45][46][47][48][49]. In this study, we also considered the assessment of PAX1 methylation levels.…”

Section: Comparison With Previous Studiesmentioning

confidence: 99%

PAX1 methylation as a robust predictor: developing and validating a nomogram for assessing endocervical curettage (ECC) necessity in human papillomavirus16/18-positive women undergoing colposcopy

Lu,

Wu,

et al. 2024

Clin Epigenet

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Objective The major challenge in routine endocervical curettage (ECC) among Human Papillomavirus (HPV) 16/18-positive patients is that only a small fraction benefit. Nevertheless, current reported models often overestimate the validity and necessity of ECC, making it difficult to improve benefits for patients. This research hypothesized that assessing paired boxed gene 1 methylation levels (PAX1m) and clinical characteristics could enhance the predictive accuracy of detecting additional high-grade squamous intraepithelial lesions or worse (HSIL +) through ECC that were not identified by colposcopy-directed biopsy (CDB). Methods Data from 134 women with HPV16/18 positivity undergoing CDB and ECC between April 2018 and April 2022 were collected and analyzed. Quantitative methylation-specific polymerase chain reaction (qMSP) was utilized to measure PAX1m, expressed as ΔCp. Univariate and multivariate regression analyses were conducted to screen variables and select predictive factors. A nomogram was constructed using multivariate logistic regression to predict additional HSIL + detected by ECC. The discrimination, calibration, and clinical utility of the nomogram were evaluated using receiver operating characteristic curves (ROC) and the calibration plot. Results Age (odds ratio [OR], 5.654; 95% confidence interval [CI], 1.131–37.700), cytology (OR, 24.978; 95% CI, 3.085–540.236), and PAX1 methylation levels by grade (PAX1m grade) (OR, 7.801; 95% CI, 1.548–44.828) were independent predictive factors for additional detection of HSIL + by ECC. In HPV16/18-positive women, the likelihood of additional detection of HSIL + through ECC increased with the severity of cytological abnormalities, peaking at 43.8% for high-grade cytological lesions. Moreover, when cytological findings indicated low-grade lesions, PAX1 methylation levels were positively correlated with the additional detection of HSIL + by ECC (P value < 0.001). A nomogram prediction model was developed (area under curve (AUC) = 0.946; 95% CI, 0.901–0.991), demonstrating high sensitivity (90.9%) and specificity (90.5%) at the optimal cutoff point of 107. Calibration analysis confirmed the model’s strong agreement between predicted and observed probabilities. Conclusion The clinical nomogram presented promising predictive performance for the additional detection of HSIL + through ECC among women with HPV16/18 infection. PAX1 methylation level could serve as a valuable tool in guiding individualized clinical decisions regarding ECC for patients with HPV 16/18 infection, particularly in cases of low-grade cytological findings.

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Triage by PAX1 and ZNF582 Methylation in Women With Cervical Intraepithelial Neoplasia Grade 3: A Multicenter Case–Control Study

Cited by 6 publications

References 34 publications

The role of PAX1 methylation in predicting the pathological upgrade of cervical intraepithelial neoplasia before cold knife conization

The role of PAX1 methylation in predicting the pathological upgrade of cervical intraepithelial neoplasia before cold knife conization

Platelet-to-Lymphocyte Ratio (PLR) as the Prognostic Factor for Recurrence/Residual Disease in HSIL Patients After LEEP

PAX1 methylation as a robust predictor: developing and validating a nomogram for assessing endocervical curettage (ECC) necessity in human papillomavirus16/18-positive women undergoing colposcopy

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