p16/Ki-67 dual staining in cervico-vaginal cytology: correlation with histology, Human Papillomavirus detection and genotyping in women undergoing colposcopy

Gynecol Oncol. 2012 Aug;126(2):198-202. doi: 10.1016/j.ygyno.2012.05.004. Epub 2012 May 12.

Abstract

Objectives: To evaluate the CINtec PLUS assay (mtm laboratories), a new immunocytochemical method for the simultaneous detection of p16(INK4a) and Ki-67, in liquid-based cervico-vaginal cytology, investigating the association of the dual staining with HPV infection and genotyping as well as cytological and histological abnormalities.

Methods: 140 women with a cervico-vaginal sample obtained immediately before the colposcopy were enrolled. This cytological sample was used for HPV testing with the Linear Array HPV Genotyping Test, the dual staining with the CINtec PLUS kit and the morphology assessment.

Results: Cytology results were 38 NILM, 16 ASC-US, 32L-SIL, 54H-SIL or worse. 113 patients also had a colposcopy-guided biopsy, classified as 14 negative, 35 CIN1, 24 CIN2, 37 CIN3, 3 invasive SCC. A strong association between p16/Ki-67 and HR-HPV infection was found (COR=6.86, 95% CI: 1.84-31.14). Importantly, the association between p16/Ki-67 positivity and HPV16 and/or 18 infection was 2-fold stronger compared to that with the infection by other HR-HPV types (COR=9.92, 95% CI: 2.39-47.77 vs COR=4.20, 95% CI: 0.99-20.87). In addition, p16/Ki-67 positivity rate significantly increased with the severity of the cytological and histological abnormalities (p<0.05 in both cases). p16/Ki-67 positivity resulted strongly associated with a CIN2+ diagnosis (COR=10.86 95% CI: 4.16-29.12).

Conclusions: This preliminary study evidenced that p16/Ki-67 immunostaining might have a relevant clinical role, since the dual staining was significantly associated with HR-HPV infection, particularly with HPV 16 and 18, and the increasing grade of the cervical lesions, the positivity for this biomarker being strongly related to the presence of a CIN2+ lesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cervix Uteri / cytology*
  • Cervix Uteri / pathology
  • Cervix Uteri / virology
  • Colposcopy / methods
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cytodiagnosis / statistics & numerical data
  • Female
  • Genotype
  • Humans
  • Immunoenzyme Techniques
  • Immunohistochemistry
  • Ki-67 Antigen / chemistry
  • Ki-67 Antigen / metabolism*
  • Middle Aged
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / metabolism*
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / pathology
  • Papillomavirus Infections / virology
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology
  • Vagina / cytology*
  • Vagina / pathology
  • Vagina / virology
  • Vaginal Smears / methods
  • Young Adult

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Ki-67 Antigen
  • Neoplasm Proteins