Prognostic Relevance of HPV Infection and p16 Overexpression in Squamous Cell Anal Cancer
- Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany)
- Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, and Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center, Heidelberg (Germany)
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland (United States)
- Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Mannheim (Germany)
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.
- OSTI ID:
- 22645006
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 4 Vol. 93; ISSN IOBPD3; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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