p16INK4a is a Useful Marker of Human Papillomavirus Integration Allowing Risk Stratification for Cervical Malignancies

  • Cheah, Phaik-Leng (Department of Pathology, Faculty of Medicine, University of Malaya) ;
  • Looi, Lai-Meng (Department of Pathology, Faculty of Medicine, University of Malaya) ;
  • Teoh, Kean-Hooi (Department of Pathology, Faculty of Medicine, University of Malaya) ;
  • Mun, Kein-Seong (Department of Pathology, Faculty of Medicine, University of Malaya) ;
  • Nazarina, Abdul Rahman (Department of Pathology, Faculty of Medicine, University of Malaya)
  • Published : 2012.02.29


The present study was conducted to assess utility of $p16^{INK4a}$ immunopositivity as a surrogate marker for genomic integration of high-risk human papillomavirus infection (hrHPV). A total of 29 formalin-fixed, paraffin-embedded cervical low-grade squamous intraepithelial lesions (LSILs), 27 high-grade squamous intraepithelial lesions (HSILs) and 53 invasive squamous cell carcinomas (SCCs), histologically-diagnosed between 1st January 2006 to 31st December 2008 at the University of Malaya Medical Centre were stained for $p^{16INK4a}$ (CINtec Histology Kit (REF 9511, mtm laboratories AG, Heidelberg, Germany). Immunopositvity was defined as diffuse staining of the squamous cell cytoplasm and or nucleus (involving > 75% of the intraepithelial lesions or SCCs). Staining of basal and parabasal layers of intraepithelial lesions was pre-requisite. One (3.4%) LSIL, 24 (88.9%) HSIL and 46 (86.8%) SCC were $p^{16INK4a}$ immunopositive. All normal squamous epithelium did not express $p16^{INK4a}$. $p16^{INK4a}$ expression was significantly lower (p<0.05) in LSIL compared with HSIL and SCC with no difference in expression between HSIL and SCC. The increased $p16^{INK4a}$ immunopositivity in HSIL and SCC appears in line with the integrated existence of the hrHPV and may provide more insightful information on risk of malignant transformation of cervical squamous intraepithelial lesions than mere hrHPV detection.


$p^{16INK4a}$ immunohistochemistry;high risk human papillomavirus;cervix;invasive squamous carcinoma


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