Efficiency of immunohistochemical p16 expression and HPV typing in cervical squamous intraepithelial lesion grading and review of the p16 literature

Pathol Res Pract. 2007;203(6):445-9. doi: 10.1016/j.prp.2007.03.010. Epub 2007 May 31.


Diagnosing and grading cervical cancer precursors is challenging. This study investigates the presence of HPV infection, the expression of p16, and any correlation between these two findings. H&E-stained slides of cervical loop excision materials diagnosed as LSIL and HSIL were reviewed. An immunohistochemical panel consisting of p16 as well as of all HPV types and HR-HPV types was applied. Staining of p16 was evaluated according to distribution extent and degree of intensity. All HSIL cases and 80% of LSIL cases were positive for p16. In HSIL cases, the staining distribution was as follows: 50% full thickness, 45% basal, and 5% rare. The staining intensity for the same cases was strong in 70%, variable in 20%, and weak in 10% accordingly. In LSIL cases, staining distribution was basal in 58.3% and rare in 41.7%. None of the LSIL cases showed full thickness of p16 positivity. The staining intensity of the same cases was strong in 25%, variable in 16.7%, and weak in 58.3%. Of all cases, 48.6% were positive for screening kit (all HPV types), and 31.4% of all cases were positive for HR-HPV. The distribution of this positivity was 35% for HSIL and 26.6% for LSIL cases. The total HPV-type positivity rate was 48.6%, the distribution being 50% for HSIL and 46.6% for LSIL cases. p16 is a highly sensitive marker for cervical epithelial dysplasia. Strong and full thickness staining of p16 in the cervix epithelium is highly supportive of HSIL, while weak and basal/rare staining favors LSIL. All HPV-positive cases were also p16-positive, but no statistically significant relationship between HPV infection positivity and the intensity and distribution of p16 was found. HPV is not helpful in the grading of SIL, as an unignorable rate of HR-HPV positivity (26.6%) was detected in LSIL group.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Cervical Intraepithelial Neoplasia / chemistry
  • Cervical Intraepithelial Neoplasia / diagnosis*
  • Cervical Intraepithelial Neoplasia / virology
  • Cervix Uteri / chemistry
  • Cervix Uteri / pathology
  • Cervix Uteri / virology
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis*
  • Female
  • Humans
  • Immunohistochemistry*
  • Neoplasms, Squamous Cell / chemistry
  • Neoplasms, Squamous Cell / diagnosis*
  • Neoplasms, Squamous Cell / virology
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / virology
  • Predictive Value of Tests
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Uterine Cervical Dysplasia / chemistry
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / chemistry
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / virology


  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16