Evaluation of the 8th TNM classification on p16-positive oropharyngeal squamous cell carcinomas in the Netherlands, and the importance of additional HPV DNA-testing
Menée auprès d'une cohorte de 388 patients atteints d'un carcinome épidermoïde de l'oropharynx exprimant la protéine p16, cette étude compare la performance de la septième et de la huitième édition du système de classification TNM pour prédire la survie des patients puis évalue l'intérêt d'ajouter, à une analyse immunohistochimique de l'expression de la protéine p16, un test de recherche de l'ADN du papillomavirus humain pour établir le pronostic avec plus de précision
Background : Oropharyngeal squamous cell carcinomas (OPSCCs) are traditionally caused by smoking and excessive alcohol consumption. However, in the last decades high-risk human papillomavirus (HR-HPV) infections play an increasingly important role in tumorigenesis. HPV-driven OPSCCs are known to have a more favorable prognosis, which has led to important and marked changes in the recently released TNM-8. In this edition, OPSCCs are divided based on p16-immunostaining, with p16-overexpression as surrogate marker for the presence of HPV. The aims of this study are to evaluate TNM-8 on a Dutch consecutive cohort of patients with p16-positive OPSCC and to determine the relevance of additional HPV DNA-testing.
Patients and methods : All OPSCC patients without distant metastases at diagnosis and treated with curative intent at VU University Medical Center (2000-2015) and Erasmus Medical Center (2000-2006) were included (N = 1,204). HPV-status was established by p16-immunostaining followed by HPV DNA-PCR on the p16-immunopositive cases. We compared TNM-7 and TNM-8 using the Harrell’s C index.
Results : In total, 388 of 1,204 (32.2%) patients were p16-immunopositive. In these patients, TNM-8 had a markedly better predictive prognostic power than TNM-7 (Harrell’s C index 0.63 versus 0.53). Of the 388 p16-positive OPSCCs, 48 tumors (12.4%) were HPV DNA-negative. This subgroup had distinct demographic, clinical and morphologic characteristics and showed a significantly worse five-year overall survival compared to the HPV DNA-positive tumors (P < 0.001).
Conclusions : TNM-8 has a better predictive prognostic power than TNM-7 in patients with p16-positive OPSCC. However, within p16-positive OPSCCs there is an HPV DNA-negative subgroup with distinct features and a worse overall survival, indicating the importance to perform additional HPV DNA-testing when predicting prognosis and particularly for selecting patients for de-intensified treatment regimens.
Annals of Oncology , résumé, 2017