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

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 guide prognosis and adjuvant therapy decisions in surgically-managed HPV-positive OPSCC.

Defining the Prevalence and Prognostic Value of Perineural Invasion and Angiolymphatic Invasion in Human Papillomavirus–Positive Oropharyngeal Carcinoma

“…7 Development of this new staging system was motivated by data from the Washington University School of Medicine, but information on its efficacy when used clinically is limited. 8 This study therefore included an analysis of this new staging criteria, applying it to a new, independent cohort of patients.…”

Pros and Cons of the New Edition of TNM Classification of Head and Neck Squamous Cell Carcinoma

“…Similarly, those who were upstaged in pN classification presented a worse DFS (17.1 vs. 61.2%; p = 0.001) and OS (8.5% versus 37.9%; p < 0.001) [30]. Table 5 summarizes the controversial results of studies on the new TNM [9,10,28,[31][32][33][34].…”

“…Recurrence risk in locally advanced HPV-positive HNSCC was higher in patients with numerous nodes involved rather than a single node or a few (< 4) large nodes [10]. Haughey et al [10] proposed a system based on the existing AJCC/UICC pT classification, cross-tabulated with cohorts who have either < 4 or > 5 pathologically confirmed metastatic neck nodes.…”

“…Haughey et al [10] proposed a system based on the existing AJCC/UICC pT classification, cross-tabulated with cohorts who have either < 4 or > 5 pathologically confirmed metastatic neck nodes. The system employs pathology-based categorization resulting from primary surgical management and is complementary to recently published clinical staging systems 5-year OS estimates of 90% (95% CI: 87-93%), 84% (95% CI: 77-90%), and 48% (95% CI: 30-66%) for HPV path stages I (pT1 or T2 with ≤4 nodes), II (pT1 or T2 with ≥5 nodes; pT3 or pT4 with ≤4 nodes), and III (pT3 or pT4 with ≥5 nodes), respectively.…”

“…Therefore, the new clinical N classification was divided as follows: N1 is defined as ipsilateral lymph nodes < 6 cm in size, and independent of numbers (also comprising N2a and N2b of the past edition); cN2 represents lymph nodes < 6 cm in size, but with ipsilateral and contralateral found to be equal; cN3 represents lymph nodes > 6 cm in size. On the other hand, in the pathological staging the results of the Haughey study were absorbed [10].…”