Florent Milliet1, Alexandre Bozec2, Renaud Schiappa3, Julien Viotti3, Anouchka Modesto4, Olivier Dassonville2, Gilles Poissonnet2, Bruno Guelfucci5, Alain Bizeau5, Sebastien Vergez6, Agnes Dupret-Bories6, Renaud Garrel7, Nicolas Fakhry8, Laure Santini8, Benjamin Lallemant9, Guillaume Chambon9, Anne Sudaka10, Frederic Peyrade11, Esma Saada-Bouzid11, Karen Benezery12, Florence Jourdan-Soulier13, Françoise Chapel13, Anne Sophie Ramay14, Pascal Roger14, Thibault Galissier15, Valérie Coste16, Aicha Ben Lakdar17, Joanne Guerlain18, Stephane Temam18, Haitham Mirghani19, Phillipe Gorphe18, Emmanuel Chamorey3, Dorian Culié20. 1. Department of Otorhinolaryngology, University Hospital of Nice, France. 2. University Institute of the Face and Neck, Antoine Lacassagne Centre, Côte d'Azur University, Nice, France. 3. Department of Statistics, Antoine Lacassagne Centre, Côte d'Azur University, Nice, France. 4. Department of Radiotherapy, Cancer University Institute of Toulouse, Toulouse, France. 5. Department of Otorhinolaryngology and Head and Neck Surgery, Sainte Musse Hospital, Toulon, France. 6. Department of Otorhinolaryngology and Head and Neck Surgery, Cancer University Institute of Toulouse, Toulouse, France. 7. Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital of Montpellier, Montpellier, France. 8. Department of Otorhinolaryngology and Head and Neck Surgery, Public Assistance - Hospitals of Marseille, Marseille, France. 9. Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital of Nîmes, Nîmes, France. 10. Department of Pathology, Antoine Lacassagne Centre, Côte d'Azur University, Nice, France. 11. Department of Medical Oncology, Antoine Lacassagne Centre, Côte d'Azur University, Nice, France. 12. Department of Radiotherapy, Antoine Lacassagne Centre, Côte d'Azur University, Nice, France. 13. Department of Pathology, Sainte Musse Hospital, Toulon, France. 14. Department of Pathology, University Hospital of Nîmes, Nîmes, France. 15. Department of Pathology, Cancer University Institute of Toulouse, Toulouse, France. 16. Department of Pathology, University Hospital of Montpellier, Montpellier, France. 17. Department of Pathology, Gustave Roussy Institute, Villejuif, France. 18. Department of Otorhinolaryngology and Head and Neck Surgery, Gustave Roussy Institute, Villejuif, France. 19. Otolaryngology and Head and Neck Surgery Department, European Hospital Georges Pompidou, APHP, Paris, France. 20. University Institute of the Face and Neck, Antoine Lacassagne Centre, Côte d'Azur University, Nice, France. Electronic address: dorian.culie@nice.unicancer.fr.
Abstract
INTRODUCTION: Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk to develop a metachronous second primary neoplasia (MSPN). HPV and non-HPV-related OPSCC are 2 distinct entities with biological, clinical and prognostic differences. The aims of our study were to analyze the impact of tumor HPV status and other relevant clinical factors, such as tobacco and/or alcohol (T/A) consumption, on the risk and distribution of MSPN in OPSCC patients and to assess the impact of MSPN on patient survival. MATERIAL AND METHODS: All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. P16 immunohistochemical expression was used as a surrogate maker of tumor HPV status. The impact of tumor p16 status on the risk of MSPN was assessed in uni- and multivariate analyses. Overall survival (OS) was determined by Kaplan-Meier analysis. RESULTS: Among the 1291 patients included in this study, 138 (10.7%) displayed a MSPN which was preferentially located in the head and neck area (H&N), lung and esophagus. Multivariate analyses showed that p16- tumor status (p = 0.003), T/A consumption (p = 0.005) and soft palate tumor site (p = 0.009) were significantly associated with a higher risk of MSPN. We found no impact of p16 tumor status on the median time between index OPSCC diagnosis and MSPN development, but a higher proportion of MSPN arising outside the H&N, lung and esophagus was found in p16 + than in p16- patients. MSPN development had an unfavorable impact (p = 0.04) on OS only in the p16 + patient group. CONCLUSION: P16 tumor status and T/A consumption were the main predictive factors of MSPN in OPSCC patients. This study provides crucial results with a view to tailoring global management and follow-up of OPSCC patients.
INTRODUCTION: Patients with oropharyngeal squamous cell carcinoma (OPSCC) display a significant risk to develop a metachronous second primary neoplasia (MSPN). HPV and non-HPV-related OPSCC are 2 distinct entities with biological, clinical and prognostic differences. The aims of our study were to analyze the impact of tumor HPV status and other relevant clinical factors, such as tobacco and/or alcohol (T/A) consumption, on the risk and distribution of MSPN in OPSCC patients and to assess the impact of MSPN on patient survival. MATERIAL AND METHODS: All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. P16 immunohistochemical expression was used as a surrogate maker of tumor HPV status. The impact of tumor p16 status on the risk of MSPN was assessed in uni- and multivariate analyses. Overall survival (OS) was determined by Kaplan-Meier analysis. RESULTS: Among the 1291 patients included in this study, 138 (10.7%) displayed a MSPN which was preferentially located in the head and neck area (H&N), lung and esophagus. Multivariate analyses showed that p16- tumor status (p = 0.003), T/A consumption (p = 0.005) and soft palate tumor site (p = 0.009) were significantly associated with a higher risk of MSPN. We found no impact of p16 tumor status on the median time between index OPSCC diagnosis and MSPN development, but a higher proportion of MSPN arising outside the H&N, lung and esophagus was found in p16 + than in p16- patients. MSPN development had an unfavorable impact (p = 0.04) on OS only in the p16 + patient group. CONCLUSION: P16 tumor status and T/A consumption were the main predictive factors of MSPN in OPSCC patients. This study provides crucial results with a view to tailoring global management and follow-up of OPSCC patients.