Oropharyngeal squamous cell carcinoma (OPSCC) has historically been attributable to tobacco and alcohol exposure and saw a decline in incidence after societal norms shifted away from smoking. In recent decades, this disease has had a re-emergence due to human papillomavirus (HPV) infection, now surpassing cervical cancer as the number 1 cause of HPV-related cancer in the United States. HPVpositive OPSCC differs from HPV-negative disease in epidemiology, prognosis, treatment, and prevention. Additionally, there is a deficit in awareness of the causal relationship between HPV and OPSCC. This, coupled with low vaccination rates, puts primary care providers in a unique position to play a vital role in prevention and early diagnosis. In this review, we highlight the epidemiology, screening, patient presentation, diagnosis, prognosis, and prevention of HPV-positive OPSCC, with a focus on the primary care provider's role.
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