Yoshifumi Yamamoto1, Norihiko Takemoto1, Takahiro Michiba1, Yuji Seo2, Fumiaki Isohashi2, Keisuke Otani2, Motoyuki Suzuki1, Takashi Fujii3, Tadashi Yoshii3, Kenji Mitani4, Toshimichi Yasui1, Hironori Cho1, Yasuhiko Tomita5,6, Eiichi Morii7, Teruki Teshima8, Kazuhiko Ogawa2, Hidenori Inohara9. 1. Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. 2. Department of Radiation Oncology, Osaka University School of Medicine, Suita, Osaka, Japan. 3. Department of Head and Neck Surgery, Osaka International Cancer Institute, Osaka, Osaka, Japan. 4. Department of Otolaryngology, Toyonaka Municipal Hospital, Toyonaka, Osaka, Japan. 5. Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Osaka, Japan. 6. Department of Pathology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Chiba, Japan. 7. Department of Pathology, Osaka University School of Medicine, Suita, Osaka, Japan. 8. Department of Radiation Oncology, Osaka International Cancer Institute, Osaka, Osaka, Japan. 9. Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. hinohara@ent.med.osaka-u.ac.jp.
Abstract
BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumor p16 and HPV DNA status with survival after radiotherapy alone remains unknown. METHODS: We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumor p16 and HPV DNA status, using Cox's proportional hazard model. RESULTS: Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality. CONCLUSIONS: Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC.
BACKGROUND:Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumorp16 and HPV DNA status with survival after radiotherapy alone remains unknown. METHODS: We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumorp16 and HPV DNA status, using Cox's proportional hazard model. RESULTS: Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality. CONCLUSIONS: Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC.
Entities:
Keywords:
De-intensified treatment; Human papillomavirus; Oropharyngeal carcinoma; Radiotherapy alone
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