title: Management of locally advanced HPV-related oropharyngeal squamous cell carcinoma: where are we?
abstract: 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.
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Samuels
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
authors.affiliation: Departments of Radiation Oncology, Otolaryngology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Beitler
authors.affiliation: Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
authors.forename: June
authors.initials: J
authors.lastname: Corry
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Carol R
authors.initials: CR
authors.lastname: Bradford
authors.affiliation: Department of Hematology and Medical Oncology, The Winship Cancer Institute of Emory University, Atlanta, GA, USA.
authors.forename: Nabil F
authors.initials: NF
authors.lastname: Saba
authors.affiliation: Department of Head and Neck Surgery and Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Michiel W M
authors.initials: MW
authors.lastname: van den Brekel
authors.affiliation: Department of Radiation Oncology, The Prince of Wales Cancer Centre, Sydney, NSW, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Smee
authors.affiliation: Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia.
authors.forename: Primož
authors.initials: P
authors.lastname: Strojan
authors.affiliation: Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain.|Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Suárez
authors.affiliation: Department of Radiation Oncology, University of Florida, Gainesville, FL, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Mendenhall
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Takes
authors.affiliation: Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain.|Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Rodrigo
authors.affiliation: Division of Oncology, Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Missak
authors.initials: M
authors.lastname: Haigentz
authors.affiliation: Department of Head and Neck Surgery, Greek Anticancer Institute, Saint Savvas Hospital, Athens, Greece.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Rapidis
authors.affiliation: University of Udine School of Medicine, Udine, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rinaldo
authors.affiliation: Coordinator of the International Head and Neck Scientific Group, Padua, Italy. a.ferlito@uniud.it.
authors.forename: Alfio
authors.initials: A
authors.lastname: Ferlito
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D057605:Natural Orifice Endoscopic Surgery; D009959:Oropharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications* / Q000378:metabolism; D011379:Prognosis; D011836:Radiation Tolerance; D012907:Smoking / Q000009:adverse effects / Q000401:mortality; D019139:Tumor Escape
chemical_list: D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: Cetuximab; EGFR; HPV; Hypoxia; Oropharyngeal carcinoma; Radiosensitivity; TORS; Treatment de-intensification; p16