IMPORTANCE: The rapid increase of human papillomavirus-associated oropharyngeal cancer has demonstrated a need for new strategies in prevention, diagnosis, evaluation, and treatment. Because there are currently no available screening technologies to detect early disease, a trend of purely incidentally identified asymptomatic p16-positive squamous cell carcinoma has been observed. We identify and describe a case series of these patients. OBSERVATIONS: A total of 134 patients with p16-positive oropharyngeal cancer were identified. Of these patients, 5 (3.7%) were identified as having completely asymptomatic primary site p16-positive tumors found during workup for other nonrelated medical problems. Four patients were found with early T-stage disease without nodal metastasis, and underwent surgical treatment as a single modality. One patient had advanced-stage disease and underwent chemoradiation. At a mean follow-up of 12.6 months, all patients remained disease free. CONCLUSIONS AND RELEVANCE: With the rise of p16-positive oropharyngeal squamous cell carcinoma and lack of screening technologies for early-stage disease, purely incidentally diagnosed disease might increase in incidence. These findings underscore the importance of a comprehensive physical examination on all patients. Although follow-up is too limited for definitive conclusions, early experience suggests that these patients can be treated with unimodality therapy when presenting with stage I or II disease.
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