Epstein-Barr virus infection is strictly associated with the metastatic spread of sinonasal squamous-cell carcinomas.
BACKGROUND
Sinonasal squamous-cell carcinomas (SNSCC) are relatively rare. Thus, data regarding the rate of lymph node metastases are inconsistent in contrast with well-known high metastasis rates in squamous-cell carcinomas of the head and neck (HNSCC) (oral cavity, pharynx and larynx). Hence, the indication for elective neck dissection is difficult in SNSCC. The aim of this study was to assess common genetic alterations and EBV and HPV status as a function of metastasis in SNSCC and HNSCC.


METHODS
We retrospectively analyzed 44 SNSCC and 65 HNSCC for TP53, EGFR, KRAS, PIK3CA and BRAF mutations using a high-resolution melting analysis followed by Sanger sequencing. EBV and HPV detection was performed using in situ hybridization for virus encoded RNA. Tumor-associated p16(INK4a) expression was visualized by immunohistochemistry and correlated with HPV infection. The mutation data, EBV and HPV status were statistically compared with the clinical data in SNSCC and HNSCC.


RESULTS
TP53 mutations were exclusively associated with shorter survival in SNSCC (p=0.048). All the other markers had no effect on the metastasis rate and survival. In total, 20 of 44 SNSCC were EBV-positive. Only these EBV positive tumors developed lymph node or distant metastases (p=0.008). LMP1 was positive in 14/44 patients. When combining both methods significance for a correlation between EBV/LMP1 positive patients and metastases was even higher (p=0.001).


CONCLUSIONS
In SNSCC, the presence of EBV is strictly associated with metastasis. We recommend an elective neck dissection in patients with EBV-positive SNSCC.
Department of Otolaryngology, Head and Neck Surgery, University of Ulm, Prittwitzstr. 43, 89075 Ulm, Germany.
Johannes
J
Doescher
Department of Otolaryngology, Head and Neck Surgery, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany.
Guido
G
Piontek
Department of Otolaryngology, Head and Neck Surgery, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany.
Markus
M
Wirth
Molecular Pathology South Bavaria, Trogerstraße 18, 81675 Munich, Germany.
Marcus
M
Bettstetter
Division of Neuropathology, Institute of Pathology, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany.
Juergen
J
Schlegel
Institute for Medical Statistics and Epidemiology, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany.
Bernhard
B
Haller
Department of Gynecology and Obstetrics, University of Regensburg, Landshuter Str. 65, 93053 Regensburg, Germany.
Gero
G
Brockhoff
Department of Otolaryngology, Head and Neck Surgery, University of Ulm, Prittwitzstr. 43, 89075 Ulm, Germany.
Rudolf
R
Reiter
Department of Otolaryngology, Head and Neck Surgery, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany. Electronic address: a.pickhard@lrz.tum.de.
Anja
A
Pickhard
D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010255:Paranasal Sinus Neoplasms / Q000473:pathology* / Q000821:virology; D000077195:Squamous Cell Carcinoma of Head and Neck
EBV; Metastasis; Sinonasal squamous cell carcinoma