P16 immunostaining and HPV testing in histological specimens from the uterine cervix

Eur J Gynaecol Oncol. 2013;34(3):227-30.

Abstract

Background: The cellular tumor suppressor protein pl61NK4a (p16) has been identified as a biomarker for transforming human papilloma virus (HPV) infections. P16 is a cyclin-dependent kinase inhibitor that regulates the cell cycle and cell proliferation by inhibiting cell cycle G1 progression.

Purpose of the study: To confirm the role of p16 as biomarker for transforming HPV infections and possible clinical applications in histological samples from the uterine cervix.

Materials and methods: The subject of this study included 56 biopsies of the cervical canal collected from January 2012 to September 2012 in the Institute of Pathology of the University of Sassari. The search for HPV immunohistochemistry was performed with the monoclonal antibody DAKO 1:25, while for the detection of p16 was used CINtecTM p16 (INK4a) histology kit.

Results: In 56 biopsies performed in women aged between 23 and 69 years, the authors highlighted, by histological analysis, 24 cases of low-grade squamous intraepithelial lesion (LSIL) - cervical intraepithelial neoplasia (CIN1) and 31 cases of high-grade squamous intraepithelial lesion (HSIL) - CIN2/3); 15 CIN2, 14 CIN3, and two cervical squamous cell carcinoma in situ (SCIS). One case was an infiltrating squamous cell carcinoma (ISC). In 24 CIN1, there was a 16.67% positivity for p16 and an equal percentage occurred for HPV. In 15 cases of CIN2 the percentage of positivity for p16 was considerably increased (73.33%), unlike the search for HPV which had a positivity rate of 20%. Finally, in 14 cases of CIN3, and in three carcinomas, the positivity for p16 was equal to 100%, however the search for HPV positivity was between 0% and 7.14%.

Conclusions: These results demonstrated that p16 was a highly sensitive marker of cervical dysplasia. The authors have shown that p16 overexpression increased with the severity of cytological abnormalities and that had a greater ability to identify the viral infection compared to the classical immunohistochemical staining for HPV.

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • Cell Transformation, Neoplastic
  • Cervix Uteri / chemistry*
  • Cervix Uteri / pathology
  • Cervix Uteri / virology
  • Cyclin-Dependent Kinase Inhibitor p16
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Proteins / analysis*
  • Papillomaviridae / isolation & purification*
  • Uterine Cervical Dysplasia / chemistry*
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / chemistry*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology

Substances

  • Biomarkers
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins