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Objective <p>Cervical intraepithelial neoplasia grade 3 (CIN 3)-like squamous cell carcinoma (SCC) is a recently identified subtype of cervical cancer with a deceptive growth pattern. It mimics the phenotype of CIN 3, involving endocervical crypts, presenting significant challenges and potential for diagnostic confusion. This study aims to clarify the differences in epigenetic profiles and HPV viral load(VL) among CIN 3, CIN 3-like SCC, early invasive SCC, and invasive SCC.</p> Methods <p>A retrospective analysis was conducted on 138 cases of cervical high-grade lesions and SCC diagnosed at Peking University People's Hospital from March 2022 to June 2024. The cases included 65 high-grade squamous intraepithelial lesions (HSIL) [23 CIN 2 and 42 CIN 3] and 73 SCC [27 CIN 3-like SCC, 21 early invasive SCC, and 25 invasive SCC]. Histological samples were analyzed for methylation levels of the epigenetic factors&#xa0;PAX1&#xa0;and&#xa0;JAM3, as well as HPV VL.</p> Results <p>Methylation levels of&#xa0;PAX1&#xa0;and&#xa0;JAM3, as well as total HPV VL, were significantly higher in cervical cancer than in HSIL(&lt; 0.001). The PAX1 methylation level of CIN3 was significantly lower than that of invasive SCC, but there was no significant difference compared with CIN3 and CIN 3-like SCC; For the PAX1/JAM3 methylation levels in CIN 3-like SCC, no statistically significant differences were observed when compared with those in early invasive SCC and invasive SCC. The HPV VL in CIN 3-like SCC was significantly higher than that in CIN 3 and early invasive SCC, but no significant difference was found compared with invasive SCC. In the same stage of FIGO, although PAX1/JAM3 methylation and HPV VL (especially HPV16/18 VL) showed a tendency to increase in CIN3-like SCC compared with early invasive SCC, the difference was not significant, further expansion of sample size is needed to confirm this.</p> Conclusion <p>PAX1 and JAM3 methylation levels are significantly higher in SCC than HSIL, but no difference in methylation levels was observed between CIN 3-like SCC, early invasive SCC, and invasive SCC. Total HPV VL (especially HPV16/18 VL) in CIN3-like SCC is significantly higher than that in CIN3 and early invasive SCC, suggesting potential shared and distinct features in epigenetics and HPV VL between CIN3-like SCC and early invasive SCC, which need more molecular biology research to explore the difference.</p>

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Preliminary study on PAX1/JAM3 methylation and HPV viral load in CIN3-like squamous cell carcinoma: Are there differences from CIN3 and early invasive carcinoma?

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月10日

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  • Mingzhu Li,
  • Xiaobo Zhang,
  • Xing Zhao,
  • Jixian Wang,
  • Chao Zhao,
  • Yun Zhao,
  • Jingran Li,
  • Danhua Shen,
  • Lihui Wei

摘要

Objective

Cervical intraepithelial neoplasia grade 3 (CIN 3)-like squamous cell carcinoma (SCC) is a recently identified subtype of cervical cancer with a deceptive growth pattern. It mimics the phenotype of CIN 3, involving endocervical crypts, presenting significant challenges and potential for diagnostic confusion. This study aims to clarify the differences in epigenetic profiles and HPV viral load(VL) among CIN 3, CIN 3-like SCC, early invasive SCC, and invasive SCC.

Methods

A retrospective analysis was conducted on 138 cases of cervical high-grade lesions and SCC diagnosed at Peking University People's Hospital from March 2022 to June 2024. The cases included 65 high-grade squamous intraepithelial lesions (HSIL) [23 CIN 2 and 42 CIN 3] and 73 SCC [27 CIN 3-like SCC, 21 early invasive SCC, and 25 invasive SCC]. Histological samples were analyzed for methylation levels of the epigenetic factors PAX1 and JAM3, as well as HPV VL.

Results

Methylation levels of PAX1 and JAM3, as well as total HPV VL, were significantly higher in cervical cancer than in HSIL(< 0.001). The PAX1 methylation level of CIN3 was significantly lower than that of invasive SCC, but there was no significant difference compared with CIN3 and CIN 3-like SCC; For the PAX1/JAM3 methylation levels in CIN 3-like SCC, no statistically significant differences were observed when compared with those in early invasive SCC and invasive SCC. The HPV VL in CIN 3-like SCC was significantly higher than that in CIN 3 and early invasive SCC, but no significant difference was found compared with invasive SCC. In the same stage of FIGO, although PAX1/JAM3 methylation and HPV VL (especially HPV16/18 VL) showed a tendency to increase in CIN3-like SCC compared with early invasive SCC, the difference was not significant, further expansion of sample size is needed to confirm this.

Conclusion

PAX1 and JAM3 methylation levels are significantly higher in SCC than HSIL, but no difference in methylation levels was observed between CIN 3-like SCC, early invasive SCC, and invasive SCC. Total HPV VL (especially HPV16/18 VL) in CIN3-like SCC is significantly higher than that in CIN3 and early invasive SCC, suggesting potential shared and distinct features in epigenetics and HPV VL between CIN3-like SCC and early invasive SCC, which need more molecular biology research to explore the difference.