ABSTRACT
Distinguishing between distantly metastatic and metachronous lung primary carcinoma is challenging for patients with a history of head and neck cancer. There are implications for registry data, prognosis and related counseling, and management options, including eligibility for precision oncology trials. Patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma who were treated under a uniform clinical protocol and achieved a complete response were identified in a single-institution prospective head and neck cancer epidemiology database (n = 205). Fifteen patients presented with pulmonary nodule(s) after completion of therapy. We describe our algorithm for the evaluation of these patients, including histopathology, p16 immunohistochemistry, and HPV in situ hybridization.