Usefulness of CINtec® PLUS p16/Ki-67 double-staining in cytological screening of cervical cancer

Acta Cytol. 2011;55(5):413-20. doi: 10.1159/000331047. Epub 2011 Oct 8.


Objective: This study evaluated the usefulness of p16(INK4a)/Ki-67 as a new biomarker in the diagnosis of human papillomavirus (HPV)-related cervical lesions.

Study design: From 69 women with previous positive cytology, clinician-collected (CC) samples were obtained using a Cervex-Brush®. One month later, self-collected (SC) material was acquired using a Rovers® Viba-Brush. Liquid-based cytology specimens were prepared from both samples, and then the grades of squamous intraepithelial lesions (SIL) were determined; following immunostaining with CINtec® PLUS, HPV status was analyzed using a linear array.

Results: The mean double-positive cell scores (SCORE) in the CC samples were 3.2 in samples negative for intraepithelial lesions or malignancy, 1.3 in atypical squamous cells of undetermined significance, 87.1 in low-grade SIL, and 367 in high-grade SIL. According to HPV risk type, the mean SCORE was 16 in samples negative for HPV, 8.4 in low-risk HPV, 143 in high-risk HPV other than type 16, and 420 in HPV16 - with a statistical significance between high-risk HPV and type 16 (p < 0.05). The SCORE of the SC group was lower than that of the CC group because of the limited number of cells collected.

Conclusions: The SCORE showed a significant correlation with HPV16 compared with lesser-degree lesions. CINtec PLUS is useful as a diagnostic marker of progression of lesions and a surrogate marker of an elevated risk of high-grade lesions with HPV16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Cervical Intraepithelial Neoplasia / diagnosis*
  • Cervical Intraepithelial Neoplasia / virology
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Cytodiagnosis / statistics & numerical data*
  • Cytological Techniques
  • DNA, Viral / genetics
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Ki-67 Antigen / metabolism*
  • Middle Aged
  • Papillomaviridae / genetics
  • Papillomaviridae / isolation & purification
  • Papillomavirus Infections / complications*
  • Polymerase Chain Reaction
  • Prognosis
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / virology
  • Vaginal Smears
  • Young Adult


  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Ki-67 Antigen