Evolving Treatment Paradigms for Oropharyngeal Squamous Cell Carcinoma

Abstract

Oropharyngeal squamous cell carcinoma (OPSCC) is increasing in incidence in the United States and in many countries worldwide primarily as a result of increasing rates of human papillomavirus (HPV) infection. HPV-positive OPSCC represents a distinct disease entity from head and neck squamous cell carcinoma caused by traditional risk factors such as tobacco and alcohol, with different epidemiology, patterns of failure, and expected outcomes. Because patients with HPV-positive OPSCC have a younger median age and superior prognosis compared with their HPV-negative counterparts, they live longer with the morbidity of treatment, which can be severe. Therefore, efforts are under way to de-escalate therapy in favorable-risk patients while maintaining treatment efficacy. Additional work is being undertaken to discover new therapies that may benefit both HPV-positive and HPV-negative patient subsets. Herein, we will review the available data for the evolving treatment paradigms in OPSCC as well as discuss ongoing clinical trials.

Fig 1

Evolving strategies in human papillomavirus (HPV) –positive versus HPV-negative oropharyngeal squamous cell carcinoma. Chemo, chemotherapy; HFX, hyperfractionated; OS, overall survival; QOL, quality of life; RT, radiotherapy.

Fig 2

Acute toxicities can translate into long-term sequelae from high-dose radiotherapy.

Fig 3

Schema of Eastern Cooperative Oncology Group 3311 study, a phase II randomized trial of transoral surgical resection followed by low-dose or standard-dose intensity-modulated radiation therapy (IMRT) in resectable p16-positive locally advanced oropharyngeal squamous cell carcinoma. ECE, extracapsular extension; LVI, lymphovascular invasion; PNI, perineural invasion; TORS, transoral robotic surgery.

Fig 4

EA3143: proposed follow-up to Eastern Cooperative Oncology Group (ECOG) 1308 testing nodal radiation deintensification. cCR, clinical complete response; CT, computed tomography; HPV, human papilloma virus; IV, intravenous; OPSCC, oropharyngeal squamous cell carcinoma; PET, positron emission tomography.