Introduction: The role of Human Papillomavirus (HPV) as a causative factor in cervical metastasis from an unknown primary (CMUP) and the impact of the virus on survival is unclear. The goal of this study was to compare outcomes of patients with HPVassociated CMUP to those of patients without evidence of HPV. Study Design: Retrospective cohort. Methods: Patients diagnosed with metastatic squamous cell carcinoma (SCC) with unknown primary after a thorough workup during the last 15 years were studied. Retrospective immunohistochemical staining for p16 (a surrogate for HPV) was performed. Demographic, nodal stage, and survival data were compared based on p16 status. Results: Nineteen patients met inclusion criteria and had specimens suitable for p16 testing. Of these, 14 were positive for p16 (74%) and 5 were negative (26%). There were no differences between the two groups with respect to demographics and presenting nodal stage. The median follow-up period was 73 months for p16 positive patients and 70 months for p16 negative patients. p16 positive patients had a statistically higher overall survival at 5 years compared to p16 negative patients (100% vs. 60%, p = 0.004). Differences in 5-year disease free survival did not reach statistical significance (93% vs. 60%, p=0.17). Conclusions: The incidence of p16 positivity in CMUP is similar to that reported for oropharyngeal SCC. Our data suggests that HPV is a common etiologic agent in CMUP and, similar to other anatomic subsites within the head and neck, p16 positivity appears to confer a better prognosis.
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