Prognostic relevance of HPV infection and p16 overexpression in squamous cell anal cancer

• Verfasst von: Mai, Sabine [VerfasserIn]
• Verfasst von: Welzel, Grit [VerfasserIn]
• Verfasst von: Ottstadt, Martine [VerfasserIn]
• Verfasst von: Lohr, Frank [VerfasserIn]
• Verfasst von: Trunk, Marcus [VerfasserIn]
• Verfasst von: Wenz, Frederik [VerfasserIn]
• Titel: Prognostic relevance of HPV infection and p16 overexpression in squamous cell anal cancer
• Verf.angabe: Sabine Mai, Grit Welzel, Martine Ottstadt, Frank Lohr, Sebastin Severa, Elena-Sophie Prigge, Nicolas Wentzensen, Marcus J. Trunk, Frederik Wenz, Magnus von Knebel-Doeberitz, and Miriam Reuschenbach
• E-Jahr: 2015
• Jahr: 15 November 2015
• Umfang: 9 S.
• Fussnoten: Gesehen am 03.01.2018
• Titel Quelle: Enthalten in: International journal of radiation oncology, biology, physics
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1975
• Jahr Quelle: 2015
• Band/Heft Quelle: 93(2015), 4, Seite 819-827
• ISSN Quelle: 1879-355X
• DOI: doi:10.1016/j.ijrobp.2015.08.004
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1566834724

Abstract

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. 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. 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. 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.