Significance of Extranodal Extension in Surgically Treated HPV-Positive Oropharyngeal Carcinomas.

Squamous cell carcinomas of the head and neck are the subject of numerous current studies, especially in view of the increasing incidence of tumors induced by human papillomavirus (HPV) and the latest changes to the TNM classification of oropharyngeal squamous cell carcinoma (OPSCC). In addition to HPV status, the presence of extranodal extension of lymph node metastases represents an important risk and prognostic factor, which has now been integrated into the staging algorithm of the eighth edition of TNM classification for HPV-negative OPSCC. In the past numerous studies had shown a lack of prognostic significance of extranodal extension in HPV-associated tumors. However, extranodal extension-as a possible risk factor even in HPV-positive OPSCC-remains an important subject of current studies, which are now particularly characterized by high numbers of cases. In this paper, diagnostic methods and the prognostic significance of extranodal extension in surgically treated HPV-positive OPSCC are presented and discussed based on relevant literature, and the results of current publications are summarized. Further development of diagnostic criteria and procedures as well as international standardization of clinical diagnostics of extranodal extension should be encouraged. Several studies demonstrate that extranodal extension results in worse survival outcomes even in HPV-positive tumors, in contrast to results of previous studies. Consequently, whether the prognostic significance of extranodal extension is not actually relevant to outcome and the staging algorithm of HPV-positive OPSCC should be questioned and further analyzed.

Staging of oropharyngeal squamous cell carcinoma of the head and neck: Prognostic features and power of the 8th edition of the UICC staging manual.

INTRODUCTION: Recognizing the prognostic power differentiating HPV-associated oropharyngeal squamous cell cancer (OPSCC) from OPSCC with other causes, the UICC Cancer Staging Manual 8th edition realizes significant changes from the 7th edition. Purpose of this study was to evaluate the differences of prognostic impact between the 7th and the latest edition of TNM Classification as well as to examine risk factors like extranodal extension (ENE) and lymph node ratio (LNR) for HPV-mediated OPSCC. MATERIAL AND METHODS: The study includes 255 patients with OPSCC and initial diagnosis between 2008 and 2015. HPV status was determined according to p16 immunohistochemistry (IHC) and all patients were classified as defined by 7th and 8th edition of UICC. Prognostic influence of ENE and LNR was analyzed for patients with HPV-mediated OPSCC. RESULTS: 41.2% of the OPSCC were p16-positive. Implementation of the 8th edition of the UICC lead to a better differentiation between the respective stages. Regarding HPV-positive OPSCC, Kaplan-Meier survival curves showed a significantly better overall survival (OS) for patients with a LNR ≤10% as well as for patients with negative ENE status (p = 0.004, p = 0.008). CONCLUSION: 8th edition of UICC achieves to differentiate properly between the UICC stages. However, the staging rule of ignoring ENE in HPV-mediated OPSCC should be further analyzed. Moreover LNR might be a possible additional prognostic factor - especially regarding HPV-positive tumors.