Human papillomavirus infection in head and neck cancer: The role of the secretory leukocyte protease inhibitor

Hoffmann,Markus; Quabius,Elgar  S.; Tribius,Silke; Hebebrand,Lena; Görögh,Tibor; Halec,Gordana; Kahn,Tomas; Hedderich,Jürgen; Röcken,Christoph; Haag,Jochen; Waterboer,Tim; Schmitt,Markus; Giuliano,Anna  R.; Kast,W.  Martin

doi:10.3892/or.2013.2327

Human papillomavirus infection in head and neck cancer: The role of the secretory leukocyte protease inhibitor

Authors:
- Markus Hoffmann
- Elgar S. Quabius
- Silke Tribius
- Lena Hebebrand
- Tibor Görögh
- Gordana Halec
- Tomas Kahn
- Jürgen Hedderich
- Christoph Röcken
- Jochen Haag
- Tim Waterboer
- Markus Schmitt
- Anna R. Giuliano
- W. Martin Kast
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Affiliations: Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts University Kiel, D-24105 Kiel, Germany, Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts University Kiel, D-24105 Kiel, Germany, Department of Radiation Oncology, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany, German Cancer Research Center (DKFZ), Infection and Cancer Program (F020), D-69120 Heidelberg, Germany, Expert Team Life Sciences, Deutsche Bank AG, D-60311 Frankfurt, Germany, Institute for Medical Informatics and Statistics, University Hospital of Schleswig-Holstein, Campus Kiel, D-24015 Kiel, Germany, Institute for Pathology, Christian‑Albrechts-University Kiel, D-24105 Kiel, Germany, Institute for Pathology, Christian‑Albrechts-University Kiel, D-24105 Kiel, Germany, Center for Infection and Cancer Research, and the Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA, Departments of Molecular Microbiology and Immunology, and Obstetrics and Gynecology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA
Published online on: March 5, 2013 https://doi.org/10.3892/or.2013.2327
Pages: 1962-1968

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Abstract

We previously showed that secretory leukocyte protease inhibitor (SLPI) gene and protein expression is significantly lower in metastatic versus non-metastatic head and neck squamous cell carcinoma (HNSCC). However, we did not assess the human papillomavirus (HPV) status of these cases. Since SLPI plays a role in HIV and herpes simplex virus (HSV) infections, we hypothesized that SLPI may be involved in HPV-infected HNSCC. In HNSCC tissue (n=54), HPV DNA was determined and correlated with SLPI expression. Additionally, to investigate a possible role of smoking on SLPI expression in clinically normal mucosa, 19 patients treated for non‑malignant diseases (non-HNSCC) were analyzed for SLPI expression and correlated with smoking habits. In HNSCC patients, SLPI expression showed a significant inverse correlation with HPV status. In patients with moderate/strong SLPI expression (n=19), 10.5% were HPV-positive. By contrast, patients with absent/weak SLPI expression (n=35), 45.7% were HPV-positive. Low SLPI expression was correlated with metastasis (P=0.003) independent of HPV status. HPV-positivity was clearly associated with lymph node status (81.3% N1-3 cases). In smoking non-HNSCC patients (n=7), 42.9% showed absent/weak and 57.1% moderate/strong SLPI staining. In non-smoking non-HNSCC patients (n=10) 83.3% showed absent/weak and 16.7% moderate/strong SLPI expression. For the first time, a correlation between SLPI downregulation and HPV infection was demonstrated, suggesting that high levels of SLPI, possibly induced by environmental factors such as tobacco smoking, correlate with protective effects against HPV infection. SLPI may be a potential biomarker identifying head and neck cancer patients not at risk of developing metastases (SLPI-positive), and those at risk to be infected by HPV (SLPI-negative) and likely to develop metastases.

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