The antileukoprotease secretory leukocyte protease inhibitor (SLPI) and its role in the prevention of HPV-infections in head and neck squamous cell carcinoma

Cancer Lett. 2015 Feb 1;357(1):339-345. doi: 10.1016/j.canlet.2014.11.043. Epub 2014 Nov 24.

Abstract

Recently, we demonstrated a significant inverse correlation between HPV-infection and SLPI-expression suggesting that SLPI protects against HPV-infection of HNSCC. Here we analyzed in a single lab setting 307 formalin-fixed paraffin-embedded HNSCC cases (tonsillar n = 135; non-tonsillar: n = 172) from eight health care centers. Samples were analyzed for SLPI gene- and protein-expression. Annexin A2, its heterotetramer A2t, putatively facilitating HPV- and SLPI-cell entry, was measured to study the correlation between SLPI and annexin A2. Data were correlated with tobacco consumption and HPV-status. Overall, HPV-DNA prevalence was 23.5% (72/307); attributed to: 43.7% (59/135) tonsillar and 7.6% (13/172) non-tonsillar cases. Smoking resulted in 6.44-fold increased and HPV-infection in 3.46-fold decreased SLPI-gene expression in all HNSCC with similar significant results obtained in tonsillar and non-tonsillar SCC separately. Correlating annexin A2- and SLPI-gene expression showed a significant surplus of annexin A2 in HPV-positive tumors (4.21× more annexin A2) and 6.72× more annexin A2 than SLPI in nonsmokers in all HNSCCs and similar significant results for both tumor entities separately. The surplus of annexin A2 in non-smokers and HPV-positive patients supports our hypothesis that decreased SLPI levels facilitate HPV-infection i.e., increased SLPI-expression may protect against HPV-infection of tonsillar and non-tonsillar SCC.

Keywords: Annexin A2; HNSCC; HPV; SLPI.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Annexin A2 / biosynthesis
  • Annexin A2 / genetics
  • Annexin A2 / metabolism
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / microbiology*
  • Female
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / microbiology*
  • Humans
  • Male
  • Middle Aged
  • Papillomaviridae / growth & development*
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / prevention & control*
  • Secretory Leukocyte Peptidase Inhibitor / biosynthesis*
  • Secretory Leukocyte Peptidase Inhibitor / genetics
  • Secretory Leukocyte Peptidase Inhibitor / metabolism
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • ANXA2 protein, human
  • Annexin A2
  • SLPI protein, human
  • Secretory Leukocyte Peptidase Inhibitor