Detection of human papillomavirus-related squamous cell carcinoma cytologically and by in situ hybridization in fine-needle aspiration biopsies of cervical metastasis -: A tool for identifying the site of an occult head and neck primary

BACKGROUND. Fine-needle aspiration (FNA) biopsy often is the first diagnostic procedure performed in patients with head and neck masses. When squamous cell carcinoma (SCC) is diagnosed, proper management and improved prognosis depends on identification of the primary tumor. Recent studies have indicated that human papillomavirus (HPV) infection is associated closely with oropharyngeal SCC and that these tumors have a distinct nonkeratinizing morphology. In this study, the authors explored the value of identifying HPV-related tumors in neck metastases to determine the origin of occult primary head and neck squamous cell carcinoma (HNSCC). METHODS. Thirty FNA biopsies of neck metastases from patients with HNSCC were recovered from the authors' files from 2004 to 2005. The primary sites included 13 oropharynx, 13 oral cavity, and 4 larynx/hypopharynx. All patients had corresponding tissue samples from the neck mass and the primary carcinoma. The FNA specimens and corresponding tissue samples were classified as either nonkeratinizing SCC (NKSCC) or keratinizing SCC (KSCC). In situ hybridization for HPV (HPV-ISH) was performed using ethanol-fixed, Papanicolaoustained smears. A positive signal was defined as dark blue or black nuclear dots. Corresponding formalin-fixed, paraffin-embedded tissue sections also were processed for HPV-ISH. RESULTS. Twenty of the 30 FNA specimens were KSCC, and 10 were NKSCC. Eight of the 10 NKSCCs originated in the oropharynx, and 2 had nonoropharyngeal origin. HPV was detected in 7 of 10 NKSCCs. Ten of 30 (33%) FNA biopsies were positive for HPV, and 9 of those biopsies were metastatic from the oropharynx. Nonkeratinzing morphology or HPV-positive ISH in FNA samples significantly predicted oropharyngeal origin (P <.0069 and P <.0004, respectively). CONCLUSIONS. NKSCC in metastatic cervical lymph nodes predicted positive HPV-ISH and was strongly suggestive of an oropharyngeal primary tumor.