Immunoreactivity of p16 in anal cytology specimens: histologic correlation

Cancer. 2006 Feb 25;108(1):66-71. doi: 10.1002/cncr.21711.


Background: Cytology has been proposed as a potential screening tool in the evaluation of squamous anorectal disease in view of the morphologic similarities between anal and cervical squamous lesions. Previous studies have demonstrated that p16 overexpression correlates with the degree of dysplasia in the uterine cervix with promising results. Due to potential diagnostic pitfalls in anal cytology, p16 overexpression in these specimens was studied.

Methods: Patients with anorectal cytology who underwent follow-up biopsy within 1 year were selected. Forty-three anorectal cytologic specimens from 29 patients were selected. One slide of each case was destained. Avidin-biotin immunocytochemical studies with the monoclonal antibody CINtec p16(INK4a) were performed. The results of the p16 immunostaining were correlated with the histologic findings.

Results: Twenty-eight of the 43 cases demonstrated the presence of squamous cells immunoreactive for p16 in cytology specimens. The p16-positive cells were identified in cases of low-grade squamous intraepithelial lesion (LSIL) (n = 3 cases), high-grade squamous intraepithelial lesion (HSIL) (n = 22 cases), and invasive squamous carcinoma (n = 1 case), and in 2 cases with negative follow-up biopsies. No cell immunoreactive for p16 was found in 15 cases (5 benign cases and 10 cases with either LSIL or HSIL). The sensitivity and specificity of p16 immunoreactivity in the detection of anal intraepithelial neoplasia or carcinoma were 72% and 71%, respectively. The positive and negative predictive values were 93% and 33%, respectively.

Conclusions: The presence of p16 immunoreactivity is a good predictor of dysplasia in anal specimens. However, the sensitivity and specificity of this marker are not high.

MeSH terms

  • Adult
  • Aged
  • Anus Neoplasms / metabolism
  • Anus Neoplasms / pathology*
  • Biomarkers, Tumor / analysis*
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology*
  • Cyclin-Dependent Kinase Inhibitor p16
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasms, Squamous Cell / metabolism
  • Neoplasms, Squamous Cell / pathology*
  • Sensitivity and Specificity


  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16