title: Pathology-based staging for HPV-positive squamous carcinoma of the oropharynx.
abstract: The rapid worldwide rise in incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has generated studies confirming this disease as an entity distinct from traditional OPSCC. Based on pathology, surgical studies have revealed prognosticators specific to HPV-positive OPSCC. The current AJCC/UICC staging and pathologic nodal (pN)-classification do not differentiate for survival, demonstrating the need for new, HPV-specific OPSCC staging. The objective of this study was to define a pathologic staging system specific to HPV-positive OPSCC.
  
  
  
  Data were assembled from a surgically-managed, p16-positive OPSCC cohort (any T, any N, M0) of 704 patients from five cancer centers. Analysis was performed for (a) the AJCC/UICC pathologic staging, (b) newly published clinical staging for non-surgically managed HPV-positive OPSCC, and (c) a novel, pathology-based, "HPVpath" staging system that combines features of the primary tumor and nodal metastases.
  
  
  
  A combination of AJCC/UICC pT-classification and pathology-confirmed metastatic node count (⩽4 versus ⩾5) yielded three groups: stages I (pT1-T2, ⩽4 nodes), II (pT1-T2, ⩾5 nodes; pT3-T4, ⩽4 nodes), and III (pT3-T4, ⩾5 nodes), with incrementally worse prognosis (Kaplan-Meier overall survival of 90%, 84% and 48% respectively). Existing AJCC/UICC pathologic staging lacked prognostic definition. Newly published HPV-specific clinical stagings from non-surgically managed patients, although prognostic, showed lower precision for this surgically managed cohort.
  
  
  
  Three loco-regional "HPVpath" stages are identifiable for HPV-positive OPSCC, based on a combination of AJCC/UICC primary tumor pT-classification and metastatic node count. A workable, pathologic staging system is feasible to establish prognosis and guide adjuvant therapy decisions in surgically-managed HPV-positive OPSCC.
authors.affiliation: Head and Neck Surgery, Florida Hospital Celebration Health, Celebration, FL, USA; Department of Surgery, University of Auckland Faculty of Medicine and Health Sciences, Auckland, New Zealand. Electronic address: Bruce.Haughey.MD@flhosp.org.
authors.forename: B H
authors.initials: BH
authors.lastname: Haughey
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: P
authors.initials: P
authors.lastname: Sinha
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: D
authors.initials: D
authors.lastname: Kallogjeri
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Goldberg
authors.affiliation: Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Lewis
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Piccirillo
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Jackson
authors.affiliation: Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Moore
authors.affiliation: Pathology and Anatomical Sciences, SUNY at the University at Buffalo, Buffalo, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Brandwein-Gensler
authors.affiliation: Head and Neck Surgery, Florida Hospital Celebration Health, Celebration, FL, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Magnuson
authors.affiliation: Otolaryngology-Head and Neck Surgery, University of Alabama, Birmingham, AL, USA.
authors.forename: W R
authors.initials: WR
authors.lastname: Carroll
authors.affiliation: Otolaryngology-Head and Neck Surgery, University of Liverpool, UK; Aintree University Hospitals NHS Foundation Trust, Liverpool, UK.
authors.forename: T M
authors.initials: TM
authors.lastname: Jones
authors.affiliation: Otolaryngology-Head and Neck Surgery, University of Liverpool, UK; Aintree University Hospitals NHS Foundation Trust, Liverpool, UK.
authors.forename: M D
authors.initials: MD
authors.lastname: Wilkie
authors.affiliation: Otolaryngology-Head and Neck Surgery, University of Liverpool, UK; Aintree University Hospitals NHS Foundation Trust, Liverpool, UK.
authors.forename: A
authors.initials: A
authors.lastname: Lau
authors.affiliation: Otolaryngology-Head and Neck Surgery, University of Liverpool, UK; Aintree University Hospitals NHS Foundation Trust, Liverpool, UK.
authors.forename: N S
authors.initials: NS
authors.lastname: Upile
authors.affiliation: Aintree University Hospitals NHS Foundation Trust, Liverpool, UK; Pathology, University of Liverpool, UK.
authors.forename: Jon
authors.initials: J
authors.lastname: Sheard
authors.affiliation: Aintree University Hospitals NHS Foundation Trust, Liverpool, UK.
authors.forename: J
authors.initials: J
authors.lastname: Lancaster
authors.affiliation: Aintree University Hospitals NHS Foundation Trust, Liverpool, UK.
authors.forename: S
authors.initials: S
authors.lastname: Tandon
authors.affiliation: Centre for Oral Health Research, Newcastle University, Framlington Place, Newcastle-upon-Tyne, UK.
authors.forename: M
authors.initials: M
authors.lastname: Robinson
authors.affiliation: Clatterbridge Cancer Centre, Wirral, UK.
authors.forename: D
authors.initials: D
authors.lastname: Husband
authors.affiliation: Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: I
authors.initials: I
authors.lastname: Ganly
authors.affiliation: Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Shah
authors.affiliation: Radiation Oncology, Duke University Medical Center, Durham, NC, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Brizel
authors.affiliation: Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
authors.forename: B
authors.initials: B
authors.lastname: O'Sullivan
authors.affiliation: Head and Neck Surgery, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Ridge
authors.affiliation: Clinical Professor, Creighton Department of Surgery, Omaha, NE, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Lydiatt
mesh_terms: D000368:Aged; D052685:Alphapapillomavirus / Q000302:isolation & purification*; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000628:therapy / Q000821:virology; D018572:Disease-Free Survival; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000628:therapy / Q000821:virology; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck
keywords: Head and neck cancer; Human papillomavirus; Oropharynx cancer; P16 gene; P16-positive; Pathologic staging; Staging