Snapshot A 43-year-old man presents to the clinic with complaints of a palpable mass at the neck. He denies any fever, chills, night sweats, or pain at the lesion. He is otherwise healthy and denies smoking or drug use. The patient reports 5 sexual partners within the last month. Introduction Overview malignant growth of tissues (most commonly squamous cell) of the oropharynx, which includes base of tongue, tonsils, soft palate, uvula, and posterior/lateral walls of the pharynx Epidemiology Demographics 6th-7th decade (tobacco and alcohol) 4th-5th decade (HPV-associated) male: female ratio of 2.7:1 Risk factors tobacco (both smoked and smokeless) alcohol human papilloma virus (HPV) betel nut chewing radiation exposure periodontal disease ETIOLOGY Pathogenesis non-HPV associated continued and repeated exposure to carcinogens leads to malignancy HPV-associated associated with HPV type 16 expression of E6 and E7 oncoproteins at the host cell, leading to inactivation of tumor suppressor gene p53 and retinoblastoma proteins Associated conditions HPV infection Presentation Symptoms dysphagia odynophagia (painful swallowing) otalgia (ear pain) obstructive sleep apnea/snoring bleeding Physical exam neck mass more common patients with HPV-positive cancer Imaging All imaging modalities are used in the staging process to assess the degree of local infiltration, lymph node involvement, and presence of distant metastases or second primary tumors Computed tomography (CT) indications initial work up for staging allows for greater spatial resolution with faster acquisition time compared to MRI Magnetic resonance imaging (MRI) indications used in conjunction with CT for staing purposes allows for superior soft tissue definition compare to CT Positron emission tomography (PET) indications used in conjunction with CT/MRI for staging purposes superior for detecting regional nodal and distant metastases. Studies Labs HPV testing tested on all patients with newly diagnosed oropharyngeal squamous cell carcinoma as HPV status is incorporated into the staging system determined via p16 immunohistochemistry or polymerase chain reaction (PCR) Invasive studies laryngoscopy indicated in all patients to evaluate the primary lesion and look for second primary lesions may have exophytic (verrucous or papillipary) and ulcerated appearance biopsy with histology biopsy often obtained with operative endoscopy 90-95% squamous cell, less common histologies include verrucous carcinoma, adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma histopathologic signs include presence of mitosis, prominent nucleoli, and atypia cells tend to be moderate to poorly differentiated Differential Oral syphilis distinguishing factors patients will have positive VDRL test resolves with antibiotics Oral tuberculosis distinguishing factors granulomatous lesions and acid-fast bacilli on biopsy Treatment Nonoperative radiation therapy single modality indicated for early-stage cancers can be used as single modality or combined with surgery or chemotherapy chemotherapy can be used in conjunction with radiation (chemoradiation) indicated in advanced cancer Operative can be used as single modality treatment for early cancers radical neck dissection indicated if clinically palpable nodal disease radical neck disection removes the sternocleidomastoid muscle, internal jugular vein, submaxillary gland, and spinal accessory nerve, and leaves the carotid artery and its branches transoral laser microsurgery (TLM) and transoral robotic surgery (TORS) becoming more popular less invasive than open surgery Prognosis Tumors associated with HPV tend to respond well to treatment Complications Metastasis Airway/esophageal obstruction Death