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

B. H. Haughey, P. Sinha, D. Kallogjeri, R. L. Goldberg, J. S. Lewis, 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. HusbandI. Ganly, J. P. Shah, D. M. Brizel, B. O'Sullivan, J. A. Ridge, W. M. Lydiatt

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


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.

Original languageEnglish
Pages (from-to)11-19
Number of pages9
JournalOral Oncology
StatePublished - Nov 1 2016


  • Head and neck cancer
  • Human papillomavirus
  • Oropharynx cancer
  • P16 gene
  • P16-positive
  • Pathologic staging
  • Staging


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