MHC class I expression in HPV positive and negative tonsillar squamous cell carcinoma in correlation to clinical outcome

Int J Cancer. 2013 Jan 1;132(1):72-81. doi: 10.1002/ijc.27635. Epub 2012 Jun 7.


Human papillomavirus (HPV) is an important factor for the development of tonsillar squamous cell carcinoma (TSCC). In addition, patients with HPV-positive TSCC have a better clinical outcome than patients with HPV-negative TSCC. Although, HPV is an important prognostic marker, additional biomarkers are needed to better predict clinical outcome to individualize treatment. Hence, we examined if classical HLA HLA-A,B,C and nonclassical HLA-E,G could serve as such marker. Formalin-fixed paraffin-embedded TSCC from 150 patients diagnosed 2000-2006, earlier analyzed for HPV DNA and p16(INK4a), and treated with intention to cure were evaluated for the expression of HLA-A,B,C and HLA-E,G by immunohistochemistry. For HPV-positive TSCC a low expression of HLA-A,B,C, whereas for HPV-negative TSCC, a normal expression of HLA-A,B,C was significantly correlated to a favorable clinical outcome. These correlations were more pronounced for membrane staining of HLA-A,B,C when compared with cytoplasmatic staining. No significant correlation was found between HLA-E,G and HPV status or clinical outcome. The unexpected contrasting correlation between HLA-A,B,C expression, and clinical outcome depending on HPV, indicates essential differences between HPV-positive and HPV-negative TSCC. Furthermore, our data demonstrate that for both HPV-positive and HPV-negative TSCC, the expression of HLA-A,B,C together with HPV may serve as a useful biomarker for predicting clinical outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / virology*
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral / genetics
  • Female
  • Genes, MHC Class I*
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Papillomaviridae / genetics*
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / virology
  • Tonsillar Neoplasms / genetics*
  • Tonsillar Neoplasms / virology*


  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Neoplasm Proteins
  • P16 protein, human