BACKGROUND: Hypoxia induces stabilization of the transcription factor HIF-1alpha (HIF-1α), associated with (chemo-)radiotherapy resistance in oropharyngeal squamous cell carcinoma (SCC). We investigated the effect of HIF-1α expression on survival in relation to human papillomavirus (HPV) status in oropharyngeal SCC. METHODS: We conducted an immunohistochemical analysis of HIF-1α protein expression and downstream targets carbonic anhydrase-IX (CA-IX) and glucose transporter-1 (GLUT-1) in 274 patients with oropharyngeal SCC. Overall survival (OS) was analyzed in total and stratified for HPV status and treatment. RESULTS: In HPV-positive tumors (n = 44), HIF-1α overexpression predicted worse OS (hazard ratio [HR] = 6.23; p = .012), whereas TNM classification or treatment modality did not. In HPV-negative tumors (n = 218), advanced T and N classification and HIF-1α overexpression all independently predicted worse OS. However, the effect of HIF-1α overexpression on OS was lower in HPV-negative (HR = 1.50; p = .024) than in HPV-positive tumors. CONCLUSION: HIF-1α overexpression is associated with worse OS and characterized a subgroup of patients with HPV-positive oropharyngeal SCC with poor prognosis. Possibly, patients with HIF-1α overexpressing HPV-positive tumors should not be eligible for treatment dose deescalation.
BACKGROUND:Hypoxia induces stabilization of the transcription factor HIF-1alpha (HIF-1α), associated with (chemo-)radiotherapy resistance in oropharyngeal squamous cell carcinoma (SCC). We investigated the effect of HIF-1α expression on survival in relation to human papillomavirus (HPV) status in oropharyngeal SCC. METHODS: We conducted an immunohistochemical analysis of HIF-1α protein expression and downstream targets carbonic anhydrase-IX (CA-IX) and glucose transporter-1 (GLUT-1) in 274 patients with oropharyngeal SCC. Overall survival (OS) was analyzed in total and stratified for HPV status and treatment. RESULTS: In HPV-positive tumors (n = 44), HIF-1α overexpression predicted worse OS (hazard ratio [HR] = 6.23; p = .012), whereas TNM classification or treatment modality did not. In HPV-negative tumors (n = 218), advanced T and N classification and HIF-1α overexpression all independently predicted worse OS. However, the effect of HIF-1α overexpression on OS was lower in HPV-negative (HR = 1.50; p = .024) than in HPV-positive tumors. CONCLUSION: HIF-1α overexpression is associated with worse OS and characterized a subgroup of patients with HPV-positive oropharyngeal SCC with poor prognosis. Possibly, patients with HIF-1α overexpressing HPV-positive tumors should not be eligible for treatment dose deescalation.
Authors: Eva-Leonne Göttgens; Christian Ostheimer; Paul N Span; Jan Bussink; Ester M Hammond Journal: Br J Radiol Date: 2018-03-14 Impact factor: 3.039
Authors: Nils H Nicolay; Nicole Wiedenmann; Michael Mix; Wolfgang A Weber; Martin Werner; Anca L Grosu; Gian Kayser Journal: Eur J Nucl Med Mol Imaging Date: 2019-12-07 Impact factor: 9.236
Authors: Nadeem Riaz; Eric Sherman; Xin Pei; Heiko Schöder; Milan Grkovski; Ramesh Paudyal; Nora Katabi; Pier Selenica; Takafumi N Yamaguchi; Daniel Ma; Simon K Lee; Rachna Shah; Rahul Kumar; Fengshen Kuo; Abhirami Ratnakumar; Nathan Aleynick; David Brown; Zhigang Zhang; Vaios Hatzoglou; Lydia Y Liu; Adriana Salcedo; Chiaojung J Tsai; Sean McBride; Luc G T Morris; Jay Boyle; Bhuvanesh Singh; Daniel S Higginson; Rama R Damerla; Arnaud da Cruz Paula; Katharine Price; Eric J Moore; Joaquin J Garcia; Robert Foote; Alan Ho; Richard J Wong; Timothy A Chan; Simon N Powell; Paul C Boutros; John L Humm; Amita Shukla-Dave; David Pfister; Jorge S Reis-Filho; Nancy Lee Journal: J Natl Cancer Inst Date: 2021-06-01 Impact factor: 13.506