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

Yingnan Lu ^1,2,3, Haiyue Wu ^1,2,3, Kun Fu ^1,2,3

⁰Department of Gynecology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.

Clinical Epigenetics +

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June 7, 2024

View abstract on PubMed

Summary

A new nomogram incorporating PAX1 methylation levels and clinical factors accurately predicts high-grade squamous intraepithelial lesions or worse (HSIL+) in HPV 16/18-positive women undergoing endocervical curettage (ECC). This tool aids in selecting patients who will benefit from ECC, especially those with low-grade cytology.

Area Of Science

Gynecology
Oncology
Molecular Diagnostics

Background

Endocervical curettage (ECC) offers limited benefit for Human Papillomavirus (HPV) 16/18-positive patients.
Current models may overestimate ECC necessity, hindering patient benefit optimization.

Purpose Of The Study

To assess if paired box gene 1 methylation (PAX1m) levels and clinical characteristics improve prediction of additional high-grade squamous intraepithelial lesions or worse (HSIL+) via ECC.
To develop a predictive model for identifying HSIL+ missed by colposcopy-directed biopsy (CDB).

Main Methods

Analysis of data from 134 HPV16/18-positive women undergoing CDB and ECC.
Quantitative methylation-specific PCR (qMSP) for PAX1m measurement.
Multivariate logistic regression and nomogram construction for predicting additional HSIL+ detection by ECC.

Main Results

Age, cytology, and PAX1m grade were independent predictors of additional HSIL+ detection by ECC.
A nomogram demonstrated high accuracy (AUC=0.946) with 90.9% sensitivity and 90.5% specificity.
PAX1m levels correlated positively with additional HSIL+ detection in low-grade cytology cases.

Conclusions

The developed clinical nomogram shows strong predictive performance for additional HSIL+ detection via ECC in HPV 16/18-positive women.
PAX1m levels can guide individualized ECC decisions, particularly for patients with low-grade cytology findings.

Keywords:

DNA methylation Endocervical curettage Human papillomavirus Nomogram prediction model PAX1