Finding confidence
in the co-expression of
p16 and Ki-67

Clinical evidence is mounting to add to the support for the biomarker concept based on the combined detection of the p16 and Ki-67 proteins via slide-based immunocytochemistry.

The test has been shown to efficiently triage1

  • Equivocal or mildly abnormal cytology results (ie, ASC-US, atypical squamous cells of undetermined significance)
  • LSIL cytology results (low-grade squamous intraepithelial lesion)
  • Normal (negative) cytology in the presence of high-risk HPV (hrHPV) infection2

The simultaneous detection of both biomarkers within the same cervical epithelial cell indicates cell-cycle disruption and the likely presence of an underlying transforming HPV infection.1

p16_Ki-67_dual_biomarker_stainingDual biomarker staining:
the brown nuclear and cytoplasmic staining indicates p16 over-expression; the red nuclear staining indicates Ki-67 expression.

The test is based on the concept that p16, an anti-proliferative protein, and Ki-67, a marker of cellular proliferation, should not be overexpressed simultaneously within the same cell in cervical cytology specimens.1,3

The test indicates oncogenic transformation, and thus eliminates equivocation over morphologic abnormalities that are not pre-cancerous. Very good overall clinical accuracy has been demonstrated in key cervical cancer screening scenarios:

Overall, p16/Ki-67 dual staining has the potential to significantly reduce the number of women referred for confirmatory colposcopy.

Scenario
Primary
screening4
ASC-US
triage1
LSIL
triage1
Pap negative/
hrHPV positive
triage2
Sensitivity87%
Specificity95%
NotesSignificantly higher sensitivity than Pap cytology with no sacrifice in specificity
Read morePALMS (Primary ASC-US LSIL Marker Study)Ikenberg et al. J Natl Cancer Inst. 2013;105(20):1550-1557).
Sensitivity92%
Specificity81%
NotesSensitivity comparable to hrHPV for ≥CIN 2 with significantly higher specificity
Read moreEEMAPS (European Equivocal or Mildly Abnormal Pap Cytology Study) Schmidt et al. Cancer Cytopathol. 2011; 119(3):158-166.
Sensitivity94%
Specificity68%
NotesSensitivity comparable to hrHPV with significantly higher specificity
Read moreEEMAPS (European Equivocal or Mildly Abnormal Pap Cytology Study) Schmidt et al. Cancer Cytopathol. 2011; 119(3):158-166.
Sensitivity92%
Specificity82%
NotesDetects virtually all ≥CIN 2; only 25% of cases referred to colposcopy
Read moreWolfsburg Study Petry et al. Gynecol Oncol. 121(3):505-509.

Further reading

The following publications provide further evidence of the clinical utility of p16/Ki-67 dual staining in cervical cancer screening:

Read More

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