Somatostatin receptor 2 is highly sensitive and specific for Epstein-Barr virus-associated nasopharyngeal carcinoma

Viruses are known drivers of head and neck squamous cell carcinomas (HNSCC), particularly Epstein-Barr virus (EBV) and human papillomavirus (HPV). Both EBV-positive nasopharyngeal carcinoma (EBVNPC) and HPV-positive oropharyngeal SCC (OPSCC) can have overlapping histomorphology and molecular signatures, including nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB) pathway mutations. A recent study showed that NFKB activation in EBVNPC drives somatostatin receptor 2 (SSTR2) expression that is detectable by immunohistochemistry and by imaging with 68-Gadolinium-DOTA-peptide radioconjugate. However, whether a similar NFKB-SSTR2 signaling mechanism exists for other virus-positive HNSCC, namely HPV-positive sinonasal carcinomas and OPSCC, remains unclear. Here we examined SSTR2 expression in a cohort of EBV-positive, HPV-positive, and virus-negative HNSCC with immunohistochemistry. SSTR2 immunohistochemistry was performed on our cohort of primary and/or metastatic EBVNPC, HPV-positive sinonasal SCC, OPSCC, HPV-negative sinonasal and oral cavity SCC, and benign tonsil and adenoid tissue. For SSTR2 staining, the extent was categorized as focal, multifocal, or diffuse, and the intensity was categorized as weak, moderate, or strong. Multifocal/diffuse SSTR2 staining of any intensity was considered positive. Among primary, recurrent, and/or undifferentiated NPC, 90% showed multifocal to diffuse strong SSTR2 expression. One HPV-positive sinonasal carcinoma showed patchy SSTR2 staining. None of the remaining HPV-positive sinonasal carcinomas, OPSCC, or oral cavity HNSCC showed significant SSTR2 staining. Overall, SSTR2 is highly sensitive and specific for EBVNPC and could represent a surrogate biomarker. Among HNSCC assessed here, we recommend testing primary NPC for SSTR2 because of its relevance for diagnosis, associated imaging modalities, and its therapeutic implications for patient care.