Relationship between p16/Ki67 immunoscores and PAX1/ZNF582 methylation status in precancerous and cancerous cervical lesions in high-risk HPV-positive women

Q: What is the purpose of using the p16/Ki67 immunoscore in this study?

It provides a cumulative grading system based on p16 and Ki67 expression that helps classify cervical intraepithelial neoplasia lesions more accurately and reproducibly.

Q: How were PAX1/ZNF582 methylation and p16/Ki67 immunoscore measured?

HPV-positive paraffin-embedded specimens were analyzed, with PAX1/ZNF582 methylation determined and p16/ki67 immunoscores derived from immunohistochemical staining scores.

Q: What key relationship was observed between lesion severity and PAX1m/ZNF582m methylation?

The ΔCp values for PAX1 methylation (PAX1m) and ZNF582 methylation (ZNF582m) decreased as cervical lesion severity increased, and PAX1m/ZNF582m prevalence rose with higher immunoscores.

Sep 21, 2026

Uploaded by Levi

High-risk HPV-positive women exhibit cervical lesion severity and molecular heterogeneity that influence cervical cancer progression. The p16/Ki67 immunoscore (IS) based on p16 and Ki67 cumulative scores enables reproducible grading of CIN, while DNA methylation is an early event in carcinogenesis. This study investigates how CIN, p16/Ki67 IS, and PAX1/ZNF582 methylation are interrelated to improve risk-informed interpretation of lesion behavior.

LanguageEnglish

CategoryResearch & Report

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Pages9

Reading Time23 min

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Abstract

Background

Methods

Results

Conclusions

Background

Luo etal. BMC Cancer (2024) 24:1171 BMC Cancer [https://doi.org/10.1186/s12885-024-12920-4](https://doi.org/10.1186/s12885-024-12920-4) RESEARCH Open Access Relationship between p16/ki67 immunoscores and PAX1/ZNF582 methylation status in precancerous and cancerous cervical lesions in high-risk HPV-positive women Haijun Luo 1†, Yixiang Lian 1†, Hong Tao2, Yan Zhao 1, Zhigan Wang 1, Jing Zhou 1, Zirong Zhang 1 and Shali Jiang 1* Abstract Background The risk of cervical cancer progression in high-risk human papillomavirus (HR-HPV)-positive women is associated with cervical lesion severity and molecular heterogeneity. Classification systems based on p16 and Ki67 expression cumulative scores (0–3 each)—p16/Ki67 collectively known as an immunoscore [IS]—are an accurate and reproducible method for grading cervical intraepithelial neoplasia (CIN) lesions. Meanwhile, DNA methylation is an early event in the development of cervical cancer. Hence, this study evaluated the relationship among CIN, p16/Ki-67 IS, and PAX1/ZNF582 methylation. Methods In this study, 414 HPV-positive paraffin-embedded specimens were collected, and PAX1/ZNF582 methylation and the p16/ki67 IS were determined. A total of 43 invalid samples were excluded and 371 were included in the statistical analyses. There were 103 cervicitis, 95 CIN1, 71 CIN2, 89 CIN3, and 13 squamous cell carcinoma (SCC) cases. The association between PAX1/ZNF582 methylation and p16/Ki6 immunohistochemical staining scores was analyzed. Results The ΔCp of PAX1m (PAX1 methylation) and ZNF582m (ZNF582 methylation) decreased with cervical lesion severity (Cuzick trend test, all P < 0. 001) . The severity of the cervical lesions and p16, Ki67, and p16/Ki67 IS showed an increasing trend (Multinomial Cochran-Armitage trend test, all P < 0. 001) . The prevalence of PAX1m/ZNF582m increased with an increase in the IS of p16, Ki67, and p16/Ki67 (Cochran-Armitage trend test, all P < 0. 001) . In cervical SCC, the IS was 5–6, and the PAX1m/ZNF582m was positive. Meanwhile, heterogeneity was observed in CIN lesions: 10 cases had an IS of 3–4 and were PAX1m/ZNF582m-positive in ≤ CIN1; 1 case had an IS of 0–2 and was PAX1m/ZNF582m-positive in CIN2/3 . Conclusions Significant heterogeneity was observed in CIN lesions for p16 and Ki67 immunohistochemical staining scores and PAX1/ZNF582 methylation. This may help clinicians personalize the management of CIN based †Haijun Luo and Yixiang Lian contributed equally to this work. *Correspondence: Shali Jiang [lzrjsl@163.com](lzrjsl@163.com) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. Luo et al. BMC Cancer (2024) 24:1171 Page 2 of 9 on the predicted short-term risk of cancer progression, minimizing the rate of missed CIN1 diagnoses and incorrect treatment of CIN2/3 . Keywords PAX1 methylation, ZNF582 methylation, p16, Ki67, Immunoscore, CIN Background Persistent infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer. Most patients with grade 3 cervical intraepithelial neoplasia (

FAQs

What is the purpose of using the p16/Ki67 immunoscore in this study?

It provides a cumulative grading system based on p16 and Ki67 expression that helps classify cervical intraepithelial neoplasia lesions more accurately and reproducibly.

How were PAX1/ZNF582 methylation and p16/Ki67 immunoscore measured?

HPV-positive paraffin-embedded specimens were analyzed, with PAX1/ZNF582 methylation determined and p16/ki67 immunoscores derived from immunohistochemical staining scores.

What key relationship was observed between lesion severity and PAX1m/ZNF582m methylation?

The ΔCp values for PAX1 methylation (PAX1m) and ZNF582 methylation (ZNF582m) decreased as cervical lesion severity increased, and PAX1m/ZNF582m prevalence rose with higher immunoscores.

Sep 21, 2026

Uploaded by Levi