Assessing for primary oropharyngeal or nasopharyngeal squamous cell carcinoma from fine needle aspiration of cervical lymph node metastases.

In fine needle aspirates of cervical lymph nodes with metastatic squamous cell carcinoma (SCC), the site of origin may not be clinically evident. The distinction between oropharyngeal and nasopharyngeal primary SCC has important management consequences. In the current study, we evaluated metastatic SCC for HPV types 16, 18, 31, 33, 51 (by in situ hybridization[ISH]), p16 and ProExC (surrogate HPV markers), and Epstein Barr Virus reported in nasopharyngeal SCC. Forty patients diagnosed between 2004 and 2008, with adequate cell block material were identified. ISH for high risk HPV and EBV (EBER), and immunohistochemistry for p16 and ProExC were performed. Primary site was designated in 31 cases with 26 head and neck including 11 oropharyngeal and 2 nasopharyngeal, and 5 other sites. High risk HPV was detected in 9 cases (22.5%), p16 in 16 (40%), ProExC in 35 (87.5%), and EBER in 2 (5%). All cases with high risk HPV ISH also showed overexpression of p16. The sensitivity for HPV infection by both surrogate markers was 100%; specificity for p16 and ProExC was 78.7 and 16.1%, respectively. Seven (63.6%) oropharyngeal SCC were positive for HPV ISH and negative for EBV; one nasopharyngeal SCC (50%) was EBER positive and HPV negative. HPV and EBER detection can serve as indicators for oropharyngeal and nasopharyngeal primary SCC, respectively, however our data show that only a subset (63.6%) of oropharyngeal SCC are high risk HPV-related. Additionally, despite their high sensitivity for HPV infection, surrogate markers, especially ProExC, lack specificity.