Management of locally advanced HPV-related oropharyngeal squamous cell carcinoma: where are we?

Eur Arch Otorhinolaryngol. 2016 Oct;273(10):2877-94. doi: 10.1007/s00405-015-3771-x. Epub 2015 Oct 13.


HPV-related (HPV+) oropharyngeal cancer (OPC) has a better prognosis compared to HPV unrelated (HPV-) OPC. This review summarizes and discusses several of the controversies regarding the management of HPV+ OPC, including the mechanism of its treatment sensitivity, modern surgical techniques, chemotherapy regimens, and treatment de-intensification protocols. We also discuss and reconsider potential adverse prognostic factors such as tumor EGFR expression, tumor hypoxia, and patient smoking history, as well as the significance of retropharyngeal adenopathy. Finally, we discuss elective nodal treatment of uninvolved lymph node stations. While this review does not exhaust all controversies related to the management of HPV+ OPC, it aims to highlight some of the most clinically relevant ones.

Keywords: Cetuximab; EGFR; HPV; Hypoxia; Oropharyngeal carcinoma; Radiosensitivity; TORS; Treatment de-intensification; p16.

Publication types

  • Review

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Female
  • Humans
  • Induction Chemotherapy
  • Male
  • Middle Aged
  • Natural Orifice Endoscopic Surgery
  • Oropharyngeal Neoplasms / metabolism
  • Oropharyngeal Neoplasms / pathology
  • Oropharyngeal Neoplasms / therapy*
  • Papillomaviridae
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / metabolism
  • Prognosis
  • Radiation Tolerance
  • Smoking / adverse effects
  • Smoking / mortality
  • Tumor Escape


  • Antineoplastic Agents
  • Cyclin-Dependent Kinase Inhibitor p16