Cervical Lymph Node P16 Status in Diagnosis of the Unknown Primary

Objectives: (1) Evaluate the role of p16 status of cervical lymph node (LN) metastases in localizing carcinoma of unknown primary (CUP). (2) Compare the sensitivity, specificity, and accuracy of positron emission tomography PET scan for locating the primary site in the setting of p16 positive and p16 negative LN metastases. Methods: Retrospective review of 30 patients that were identified from archived tumor board lists from 2010 to 2013. All patients presented to a tertiary care center with squamous cell carcinoma metastases to cervical LN of unknown source despite initial clinical evaluation and computed tomography scan. Fine needle biopsy or excisional biopsy specimens were tested for the p16 biomarker. The accuracy of the PET scan was assessed by comparing the fludeoxyglucose-avid predicted site against a standard panendoscopy with directed biopsies. Results: A primary was identified in 61% of cases presenting as CUP. All p16+ LN metastases were from an oropharyngeal primary or remained unknown. All primaries located outside the upper aerodigestive tract were p16–. The sensitivity and specificity of PET in patients with p16+ LN metastases were worse than in p16- metastases (71%, 33% vs 100%, 100%). Conclusions: LN p16 status can help localize CUP. In our series, the sensitivity and specificity of PET scan were much worse in p16+ LN metastases. PET scan may be of limited utility for localizing CUP with p16+ LN metastasis.