Sabine Mai1, Grit Welzel2, Martine Ottstadt2, Frank Lohr2, Sebastin Severa2, Elena-Sophie Prigge3, Nicolas Wentzensen4, Marcus J Trunk5, Frederik Wenz2, Magnus von Knebel-Doeberitz3, Miriam Reuschenbach3. 1. Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany. Electronic address: sabine.mai@umm.de. 2. Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany. 3. Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, and Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center, Heidelberg, Germany. 4. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland. 5. Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
Abstract
PURPOSE: Human papillomavirus (HPV) DNA and p16 status have both been reported as prognostic factors in anal cancer, but the prognostic relevance of combined detection and particularly HPV-/p16+ and HPV+/p16- signatures is unknown. We evaluated combined HPV DNA and p16 status as a prognostic factor of treatment response in anal cancer. METHODS: 106 patients treated with radiochemotherapy (RCT+5-FU/MMC) with available paraffin-embedded tumor tissue specimens were evaluated regarding local control (LC) and overall survival (OS) at 5 years. In addition to HPV DNA/p16 status, the influence of age, gender, previous surgery, initial recurrence, T stage, N status, and tumor localization was analyzed. RESULTS: 63 patients were HPV+/p16+, 9 were HPV+/p16-, 11 were HPV-/p16+, and 23 were HPV-/p16-. In univariate analysis, LC was significantly better in patients with T1/2 stage, female gender, and HPV/p16 status. HPV+/p16+ was associated with significantly better LC (88.1%; 95% confidence interval [CI]: 78.89-97.31) compared with HPV-/p16+ (63.6%; 95% CI: 35.18-92.02; P=.021) and especially HPV-/p16- (55.8%; 95% CI: 33.46-78.14; P=.002) but not with HPV+/p16- (77.8%; 95% CI: 50.56-105.04; P=.270). OS was influenced by T stage and LC. HPV+/p16+ patients showed a trend toward better OS compared with HPV-/p16- patients (HPV+/p16+: 81.1%; 95% CI: 70.12-92.08 vs HPV-/p16-: 68.8%; 95%CI: 47.44-90.16; P=.138). On multivariate analysis, T3/4 stage and HPV/p16 status (HPV-/p16+, HPV-/p16- vs HPV+/p16+) predicted poorer LC (T3/4: 50.3% vs T1/2: 86.6%, hazard ratio [HR] 0.22; 95% CI: 0.09-0.53; P<.001; HPV+/p16+ vs HPV-/p16+: HR 4.73; 95% CI: 1.33-16.82; P=.016, and HPV+/p16+ vs HPV-/p16-: HR 6.40; 95% CI: 2.23-18.35; P<.001), whereas local relapse dramatically influenced OS. CONCLUSION: Our data suggest that HPV/p16 signature determines prognosis. HPV+/p16+ patients had the best prognosis, and HPV-/p16+ and HPV-/p16- patients showed the worst outcome and therefore require therapy optimization, particularly given that LC is the most important factor for OS.
PURPOSE:Human papillomavirus (HPV) DNA and p16 status have both been reported as prognostic factors in anal cancer, but the prognostic relevance of combined detection and particularly HPV-/p16+ and HPV+/p16- signatures is unknown. We evaluated combined HPV DNA and p16 status as a prognostic factor of treatment response in anal cancer. METHODS: 106 patients treated with radiochemotherapy (RCT+5-FU/MMC) with available paraffin-embedded tumor tissue specimens were evaluated regarding local control (LC) and overall survival (OS) at 5 years. In addition to HPV DNA/p16 status, the influence of age, gender, previous surgery, initial recurrence, T stage, N status, and tumor localization was analyzed. RESULTS: 63 patients were HPV+/p16+, 9 were HPV+/p16-, 11 were HPV-/p16+, and 23 were HPV-/p16-. In univariate analysis, LC was significantly better in patients with T1/2 stage, female gender, and HPV/p16 status. HPV+/p16+ was associated with significantly better LC (88.1%; 95% confidence interval [CI]: 78.89-97.31) compared with HPV-/p16+ (63.6%; 95% CI: 35.18-92.02; P=.021) and especially HPV-/p16- (55.8%; 95% CI: 33.46-78.14; P=.002) but not with HPV+/p16- (77.8%; 95% CI: 50.56-105.04; P=.270). OS was influenced by T stage and LC. HPV+/p16+ patients showed a trend toward better OS compared with HPV-/p16- patients (HPV+/p16+: 81.1%; 95% CI: 70.12-92.08 vs HPV-/p16-: 68.8%; 95%CI: 47.44-90.16; P=.138). On multivariate analysis, T3/4 stage and HPV/p16 status (HPV-/p16+, HPV-/p16- vs HPV+/p16+) predicted poorer LC (T3/4: 50.3% vs T1/2: 86.6%, hazard ratio [HR] 0.22; 95% CI: 0.09-0.53; P<.001; HPV+/p16+ vs HPV-/p16+: HR 4.73; 95% CI: 1.33-16.82; P=.016, and HPV+/p16+ vs HPV-/p16-: HR 6.40; 95% CI: 2.23-18.35; P<.001), whereas local relapse dramatically influenced OS. CONCLUSION: Our data suggest that HPV/p16 signature determines prognosis. HPV+/p16+ patients had the best prognosis, and HPV-/p16+ and HPV-/p16- patients showed the worst outcome and therefore require therapy optimization, particularly given that LC is the most important factor for OS.
Authors: V Dell'Acqua; J Kobiela; F Kraja; M C Leonardi; A Surgo; M A Zerella; S Arculeo; C Fodor; R Ricotti; M G Zampino; S Ravenda; G Spinoglio; R Biffi; A Bazani; R Luraschi; S Vigorito; P Spychalski; R Orecchia; R Glynne-Jones; B A Jereczek-Fossa Journal: Med Oncol Date: 2018-03-28 Impact factor: 3.064
Authors: Jonathan E Leeman; Yi Li; Andrew Bell; Suleman S Hussain; Rahul Majumdar; Xiaoqing Rong-Mullins; Pedro Blecua; Rama Damerla; Himanshi Narang; Pavithran T Ravindran; Nancy Y Lee; Nadeem Riaz; Simon N Powell; Daniel S Higginson Journal: Proc Natl Acad Sci U S A Date: 2019-10-07 Impact factor: 11.205
Authors: Lucas Tadeu Bidinotto; Carlos A R Véo; Edgar Aleman Loaiza; Guilherme G Ribeiro; Adriana T Lorenzi; Luciana Albina Reis Rosa; Cristina Mendes De Oliveira; José Eduardo Levi; Cristovam Scapulatempo-Neto; Adhemar Longatto-Filho; Rui Manuel Reis Journal: Oncol Lett Date: 2018-05-30 Impact factor: 2.967
Authors: Mehmet Sarier; Ali Murat Ceyhan; Nevgun Sepin; Esin Ozel; Mehmet Murat Inal; Erdal Kukul; Ahmet Soylu Journal: Int Urol Nephrol Date: 2019-10-03 Impact factor: 2.370
Authors: Jaymin Jhaveri; Lael Rayfield; Yuan Liu; Mudit Chowdhary; Richard J Cassidy; Nicholas A Madden; Daniel G Tanenbaum; Theresa W Gillespie; Pretesh R Patel; Kirtesh R Patel; Jerome C Landry Journal: J Gastrointest Oncol Date: 2017-12
Authors: D Tasic; I Lazarevic; A Knezevic; L Tasic; A Pikula; Z Perisic; T Jovanovic; M Cupic Journal: Epidemiol Infect Date: 2018-06-20 Impact factor: 4.434
Authors: Xiaoqin Zhu; Sarah Jamshed; Jian Zou; Azniv Azar; Xiuling Meng; Venu Bathini; Karen Dresser; Cara Strock; Bhargavi Yalamarti; Michelle Yang; Keith Tomaszewicz; George Tjionas; Mark C Mochel; Lloyd Hutchinson; Jacob R Bledsoe Journal: Mod Pathol Date: 2021-01-22 Impact factor: 8.209