Evaluation of PAX1/ST6GALNAC5 Methylation as a Triage Test for Cervical Intraepithelial Neoplasia and Cervical Couancer

Abstract

Aim: To identify DNA methylation markers for triage in a cohort of human papillomavirus-positive (HPV⁺) women. Methods: The methylation markers were identified and evaluated for the detection of cervical high-grade squamous intraepithelial lesions (HSILs) or cervical cancer (collectively referred to as ‘HSIL+’) in HPV⁺ women (n = 692). Results: Combined PAX1/ST6GALNAC5 methylation testing yielded HSIL+ sensitivity of 0.838 and 0.818, with a specificity of 0.827 and 0.810, in the training and test sets, respectively. For cervical cancer, the specificity and sensitivity were 0.969 and 1.000 in the training set and 0.967 and 0.875 in the test set. Moreover, the combined marker methylation test (0.86; 77/90) was more sensitive than the cytology (0.31; 28/90) for HSIL+. Conclusion: The combined PAX1/ST6GALNAC5 marker may have clinical application for detecting HSIL+ in HPV⁺ women undergoing screening.

Keywords::

• cervical intraepithelial neoplasia
• clinical performance
• cytology
• diagnostic accuracy
• epigenetic
• HPV screening
• squamous intraepithelial lesion

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2022-0396

Financial & competing interests disclosure

This work was supported by the Project of the Natural Science Foundation of Hunan Province (grant no. 2021JJ40512). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The study was approved by the Ethics Committee of the Changsha Hospital for Maternal and Child Health Care (no. 2022033) and the Second Affiliated Hospital of Soochow University (no. JD-LK-2022-010-01). All the participants provided written informed consent. All authors declare that all the figures and tables, including supplementary files, are original.

Data sharing statement

The public 450 BeadChip array methylation data are from the TCGA (https://portal.gdc.cancer.gov/) and the GEO databases GSE68339 (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE68339), GSE46306 (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE46306).

All in-house data included in this study are available upon request by contacting the corresponding author.

Additional information

Funding

This work was supported by the Project of the Natural Science Foundation of Hunan Province (grant no. 2021JJ40512). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.