ArticleCancer medicine2020
Expression of p16 and HPV E4 on biopsy samples and methylation of FAM19A4 and miR124-2 on cervical cytology samples in the classification of cervical squamous intraepithelial lesions.
Article in Cancer medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- The Role of microRNA Expression and DNA Methylation in HPV-Related Cervical Cancer: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Advances in the application of gene methylation detection in cervical cancer screening.Frontiers in oncology · 2026Review
- p16International journal of cancer · 2025Article
- Human papillomavirus (HPV) genotyping and prognostic value of HPV E4 protein and transcription factors NANOG and SOX11 in atypical p16 patchy squamous epithelium of cervix.Radiology and oncology · 2025Article
- Serum Antibodies Against the E5 Oncoprotein from Human Papillomavirus Type 16 Are Inversely Associated with the Infection and the Degree of Cervical Lesions.Biomedicines · 2024Article
- CIN grades possessing different HPV RNA location patterns and RNAscope is helpful tool for distinguishing squamous intraepithelial lesions in difficult cervical cases.Diagnostic pathology · 2023Article
- Expression of E4 Protein and HPV Major Capsid Protein (L1) as A Novel Combination in Squamous Intraepithelial Lesions.Biomedicines · 2023Article
- Adjunctive use of p16 immunohistochemistry for optimizing management of CIN lesions in a high-risk human papillomavirus-positive population.Acta obstetricia et gynecologica Scandinavica · 2022Article
- Classification of high-grade cervical intraepithelial neoplasia by p16International journal of cancer · 2021Article
- Triage of hrHPV-positive women: comparison of two commercial methylation-specific PCR assays.Clinical epigenetics · 2020Article
- Characterization of cervical biopsies of women with HIV and HPV co-infection using p16Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- Association of high-risk human papillomavirus infection duration and cervical lesions with vaginal microbiota composition.Annals of translational medicine · 2020Article
- Expression of p16 and HPV E4 on biopsy samples and methylation of FAM19A4 and miR124-2 on cervical cytology samples in the classification of cervical squamous intraepithelial lesions.Cancer medicine · 2020Article
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The decision to treat a cervical squamous intraepithelial lesion (SIL) by loop electrosurgical excision procedure (LEEP) relies heavily on a colposcopy-directed biopsy showing high-grade (H)SIL. Diagnosis is often supported by p16, an immunohistochemical (IHC) biomarker of high-risk (hr)HPV E7 gene activity. Additional potential markers include methylation of tumor suppressor genes FAM19A4/miR124-2 in cervical cytology for advanced transforming HSIL and the IHC marker HPV E4 for productive, potentially regressing lesions. In 318 women referred for colposcopy, we investigated the relationship between staining patterns of p16 and E4 IHC in the worst biopsy, and the relation of these to FAM19A4/miR124-2 methylation status in cytology. E4-positive staining decreased with increasing SIL/CIN grade from 41% in LSIL to 3% in HSIL/CIN3. E4 positivity increased with grade of p16 when p16 expression was limited to the lower two third of the epithelium (r = 0.378), but fell with expression over. Loss of E4 expression in the worst lesion was associated with the methylation of FAM19A4/miR124-2. We also examined whether these biomarkers can predict the histological outcome of the LEEP biopsy in a subgroup of 119 who underwent LEEP treatment. About 85% of women with ≥lower two third p16 staining/E4-negative HSIL biopsies and 65% with limited p16 staining/E4-positive HSIL biopsies had ≥HSIL in the LEEP specimen (P = .025). p16 expression in a biopsy is related both to viral production and transformation, while decreased E4 expression relates to methylation, indicating advanced HSIL. p16 expression in ≥2/3 of the epithelium and absent E4 indicate likely HSIL on a subsequent LEEP specimen.
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