Pathology-based staging for HPV-positive squamous carcinoma of the oropharynx

B H Haughey; P Sinha; D Kallogjeri; R L Goldberg; J S Lewis Jr; J F Piccirillo; R S Jackson; E J Moore; M Brandwein-Gensler; S J Magnuson; W R Carroll; T M Jones; M D Wilkie; A Lau; N S Upile; Jon Sheard; J Lancaster; S Tandon; M Robinson; D Husband; I Ganly; J P Shah; D M Brizel; B O'Sullivan; J A Ridge; W M Lydiatt

doi:10.1016/j.oraloncology.2016.09.004

Pathology-based staging for HPV-positive squamous carcinoma of the oropharynx

Oral Oncol. 2016 Nov:62:11-19. doi: 10.1016/j.oraloncology.2016.09.004. Epub 2016 Sep 23.

Authors

B H Haughey¹, P Sinha², D Kallogjeri², R L Goldberg², J S Lewis Jr³, J F Piccirillo², R S Jackson², E J Moore⁴, M Brandwein-Gensler⁵, S J Magnuson⁶, W R Carroll⁷, T M Jones⁸, M D Wilkie⁸, A Lau⁸, N S Upile⁸, Jon Sheard⁹, J Lancaster¹⁰, S Tandon¹⁰, M Robinson¹¹, D Husband¹², I Ganly¹³, J P Shah¹³, D M Brizel¹⁴, B O'Sullivan¹⁵, J A Ridge¹⁶, W M Lydiatt¹⁷

Affiliations

¹ 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.
² Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
³ Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
⁴ Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN, USA.
⁵ Pathology and Anatomical Sciences, SUNY at the University at Buffalo, Buffalo, NY, USA.
⁶ Head and Neck Surgery, Florida Hospital Celebration Health, Celebration, FL, USA.
⁷ Otolaryngology-Head and Neck Surgery, University of Alabama, Birmingham, AL, USA.
⁸ Otolaryngology-Head and Neck Surgery, University of Liverpool, UK; Aintree University Hospitals NHS Foundation Trust, Liverpool, UK.
⁹ Aintree University Hospitals NHS Foundation Trust, Liverpool, UK; Pathology, University of Liverpool, UK.
¹⁰ Aintree University Hospitals NHS Foundation Trust, Liverpool, UK.
¹¹ Centre for Oral Health Research, Newcastle University, Framlington Place, Newcastle-upon-Tyne, UK.
¹² Clatterbridge Cancer Centre, Wirral, UK.
¹³ Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, USA.
¹⁴ Radiation Oncology, Duke University Medical Center, Durham, NC, USA.
¹⁵ Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
¹⁶ Head and Neck Surgery, Fox Chase Cancer Center, Philadelphia, PA, USA.
¹⁷ Clinical Professor, Creighton Department of Surgery, Omaha, NE, USA.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Head and neck cancer; Human papillomavirus; Oropharynx cancer; P16 gene; P16-positive; Pathologic staging; Staging.

MeSH terms

Aged
Alphapapillomavirus / isolation & purification*
Carcinoma, Squamous Cell / pathology*
Carcinoma, Squamous Cell / therapy
Carcinoma, Squamous Cell / virology
Disease-Free Survival
Head and Neck Neoplasms / pathology*
Head and Neck Neoplasms / therapy
Head and Neck Neoplasms / virology
Humans
Middle Aged
Prognosis
Squamous Cell Carcinoma of Head and Neck

Abstract

MeSH terms

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