title: Human papillomavirus infection in head and neck cancer: the role of the secretory leukocyte protease inhibitor.
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.
authors: Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts University Kiel, D-24105 Kiel, Germany. mhoffmann@hno.uni-kiel.de
authors: Markus
authors: M
authors: Hoffmann
authors: Elgar S
authors: ES
authors: Quabius
authors: Silke
authors: S
authors: Tribius
authors: Lena
authors: L
authors: Hebebrand
authors: Tibor
authors: T
authors: Görögh
authors: Gordana
authors: G
authors: Halec
authors: Tomas
authors: T
authors: Kahn
authors: Jürgen
authors: J
authors: Hedderich
authors: Christoph
authors: C
authors: Röcken
authors: Jochen
authors: J
authors: Haag
authors: Tim
authors: T
authors: Waterboer
authors: Markus
authors: M
authors: Schmitt
authors: Anna R
authors: AR
authors: Giuliano
authors: W Martin
authors: WM
authors: Kast
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000821:virology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D011480:Protease Inhibitors / Q000378:metabolism; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral; D011480:Protease Inhibitors; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor