Role of P16(INK4a) expression in identifying CIN2 or more severe lesions among HPV-positive patients referred for colposcopy after abnormal cytology

Cancer. 2006 Apr 25;108(2):119-23. doi: 10.1002/cncr.21713.


Background: p16 is strongly overexpressed in dysplastic cervical cells because of the transforming activity of the E7 oncogene of all high-risk human papillomavirus (HR-HPV) types and may be easily revealed by immunochemistry: p16 may, therefore, be considered a surrogate marker for the activated oncogene expression of HR-HPV in dysplastic cervical cells.

Methods: HPV and p16(INK4a) testing were performed in a consecutive series of 283 patients with abnormal cytology referred to colposcopy assessment or follow-up. Triage of patients to colposcopy by HPV or HPV and p16 testing was simulated, and the relative sensitivity, specificity, and positive predictive value (PPV) of HPV and p16 testing for > CIN2 lesions was determined as well as the cost balance of the two triage types.

Results: Compared to current protocol, triage by HPV testing reduced the number of colposcopies by 44.2%, but also reduced the > CIN2 detection rate by 10.7%, and was associated with a cost of euro 54.16 per assessed woman and of euro 613.20 per > CIN2 detected. Compared with current protocol, triage by HPV and p16 testing combined reduced the number of colposcopies by 73.1%, but reduced > CIN2 detection rate by 21.5%, and was associated with a cost of euro 54.73 per woman assessed and of euro 704.09 per > CIN2 detected.

Conclusions: Triage by HPV and p16 improves considerably the PPV of diagnostic assessment, but decreases > CIN2 detection rate, and is associated with substantially higher costs. Further decrease of molecular immunochemistry testing due to technological progress may allow HPV and p16 testing to become a cost effective procedure in the future.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Cervical Intraepithelial Neoplasia / chemistry
  • Cervical Intraepithelial Neoplasia / diagnosis*
  • Cervical Intraepithelial Neoplasia / pathology
  • Cervical Intraepithelial Neoplasia / virology
  • Cervix Uteri / chemistry
  • Cervix Uteri / pathology
  • Cervix Uteri / virology
  • Colposcopy* / economics
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA, Viral / analysis
  • DNA, Viral / genetics
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Papillomaviridae* / genetics
  • Papillomaviridae* / isolation & purification
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / pathology
  • Polymerase Chain Reaction
  • Predictive Value of Tests
  • Sensitivity and Specificity
  • Uterine Cervical Neoplasms / chemistry
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology


  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral