An evaluation of p16INK4a expression in cervical intraepithelial neoplasia specimens, including women with HIV-1

Alcina F. Nicol, Jonathan E. Golub, José R.Lapa e Silva, Cynthia B. Cunha, Sergio M. Amaro-Filho, Nathalia S. Oliveira, Willker Menezes, Cecília Viana Andrade, Fabio Russomano, Aparecida Tristão, Beatriz Grinsztejn, Ruth Khalili Friedman, Marcia P. Oliveira, Andrea Pires, Gerard J. Nuovo

Research output: Contribution to journalArticlepeer-review


Although several studies have evaluated the role of p16INK4a as a diagnostic marker of cervical intraepithelial neoplasia (CIN) and its association with disease progression, studies regarding the role of p16INK4a in human immunodeficiency virus (HIV)-infected patients remain scarce. The present study was designed to determine the potential utility of p16INK4a as a diagnostic marker for CIN and invasive cervical cancer in HIV-positive and negative cervical specimens. An immunohistochemical analysis of p16INK4a was performed in 326 cervical tissue microarray specimens. Performance indicators were calculated and compared using receiving operating characteristics curve (ROC)/area under the curve. In HIV-1-negative women, the percentage of cells that was positive for p16INK4a expression was significantly correlated with the severity of CIN (p < 0.0001). A ROC curve with a cut-off value of 55.28% resulted in a sensitivity of 89%, a specificity of 81%, a positive predictive value of 91% and a negative predictive value of 78%. HIV-seropositive women exhibited decreased expression of p16INK4a in CIN2-3 specimens compared with HIV-negative specimens (p = 0.031). The ROC data underscore the potential utility of p16INK4a under defined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. HIV-1 infection, however, is associated with relatively reduced p16INK4a expression in CIN 2-3.

Original languageEnglish (US)
Pages (from-to)571-577
Number of pages7
JournalMemorias do Instituto Oswaldo Cruz
Issue number5
StatePublished - Aug 2012


  • CIN
  • HIV
  • HPV
  • ROC
  • TMA
  • p16

ASJC Scopus subject areas

  • Microbiology (medical)


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