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

Li, Mingzhu; Zhao, Chao; Zhao, Yun; Li, Jingran; Wang, Jingyuan; Luo, Hongxue; Tang, Zhen; Guo, Yan; Wei, Lihui

doi:10.3389/fonc.2022.1064722

Cited by 7 publications

(5 citation statements)

References 34 publications

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“…Moreover, PAX1 hypermethylation analysis may be preferable to hybrid capture (HC2) in triaging ASCUS and ASC-H [46]. Additionally, besides serving as an predictor for pathological upgrade of HSIL before cold knife conization [47], it may also predict the sensitivity and efficacy of concurrent chemo-radiotherapy (CCRT) in cervical cancer [48]. Furthermore, it may aid in the diagnosis of cervical adenocarcinomas [24].…”

Section: Discussionmentioning

confidence: 99%

PAX1/JAM3 Methylation and HPV Viral Load in Women with Persistent HPV Infection

Li,

Zhao,

Zhang

et al. 2024

Cancers

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The relationship of PAX1/JAM3 methylation as well as HPV viral load (VL) with cervical lesions has been reported, but their role in persistent HPV infection without cervical high-grade lesions has not been fully elucidated. A total of 231 females diagnosed with persistent HPV infection and pathologically confirmed absence of high-grade cervical lesions were selected from the Colposcopy Outpatient Clinic of Peking University People’s Hospital, from March 2023 to December 2023. They were categorized into two groups based on the duration of HPV infection: the HPV persistent less than 3 years group and the more than 3 years group. PAX1/JAM3 methylation and HPV VL were determined by real-time PCR and BioPerfectus Multiplex Real-Time (BMRT)-HPV reports type-specific VL/10,000 cells, respectively. The average age of individuals with HPV infection lasting more than 3 years was higher compared to those with less than 3 years (48.9 vs. 45.1 years), with a statistically significant difference. Among the participants, 81.8% (189/231) had no previous screening. The methylation levels of JAM3 and PAX1 were significantly higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, with a statistically significant difference (p < 0.05). There was a significant correlation between PAX1 and JAM3 methylation (p < 0.001), which could be used as cumulative evidence of HPV infection duration before the occurrence of precancerous lesions. The incidence of vaginal intraepithelial lesions was higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, and HPV VL can be used as an indicative biomarker for concurrent cervical–vaginal lesions, especially for HPV other than 16/18 genotypes.

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Section: Discussionmentioning

confidence: 99%

PAX1/JAM3 Methylation and HPV Viral Load in Women with Persistent HPV Infection

Li,

Zhao,

Zhang

et al. 2024

Cancers

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“…Cervical exfoliated cells were collected to conduct TCT and HPV screening as reported previously [ 37 ]. Briefly, a vaginal speculum was placed to expose the cervix, and cervical exfoliation was performed at the squamocolumnar junction of the cervix using sampling brushes for TCT and HPV screening separately.…”

Section: Methodsmentioning

confidence: 99%

High-Risk Genotypes of Human Papillomavirus at Diverse Anogenital Sites among Chinese Women: Infection Features and Potential Correlation with Cervical Intraepithelial Neoplasia

Zhao,

An,

et al. 2024

Cancers

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Background: Both cervical cancer and cervical intraepithelial neoplasia (CIN) are associated with human papillomavirus (HPV) infection at different anogenital sites, but the infection features of high-risk (HR) HPVs at these sites and their association with cervical lesions have not been well characterized. Given the limitation of cervical HPV 16/18 test in screening patients with high-grade CIN (CIN 2+), studies on whether non-16/18 HR-HPV subtype(s) have potential as additional indicator(s) to improve CIN 2+ screening are needed. Methods: The infection of 15 HR-HPVs in vulva, anus, vagina, and cervix of 499 Chinese women was analyzed, and CIN lesion-associated HR-HPV subtypes were revealed. Results: In addition to the well-known cervical-cancer-associated HPV 16, 52, and 58, HPV 51, 53, and 56 were also identified as high-frequency detected subtypes prevalently and consistently present at the anogenital sites studied, preferentially in multi-infection patterns. HPV 16, 52, 58, 56, and 53 were the top five prevalent subtypes in patients with CIN 2+. In addition, we found that cervical HPV 33/35/52/53/56/58 co-testing with HPV 16/18 might improve CIN 2+ screening performance. Conclusion: This study provided a new insight into HR-HPV screening strategy based on different subtype combinations, which might be used in risk stratification clinically.

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

Cited by 7 publications

References 34 publications

PAX1/JAM3 Methylation and HPV Viral Load in Women with Persistent HPV Infection

PAX1/JAM3 Methylation and HPV Viral Load in Women with Persistent HPV Infection

High-Risk Genotypes of Human Papillomavirus at Diverse Anogenital Sites among Chinese Women: Infection Features and Potential Correlation with Cervical Intraepithelial Neoplasia

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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