Christine H Chung1, Qiang Zhang2, Christina S Kong2, Jonathan Harris2, Elana J Fertig2, Paul M Harari2, Dian Wang2, Kevin P Redmond2, George Shenouda2, Andy Trotti2, David Raben2, Maura L Gillison2, Richard C Jordan2, Quynh-Thu Le2. 1. Christine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO. cchung11@jhmi.edu. 2. Christine H. Chung and Elana J. Fertig, Johns Hopkins University, Baltimore, MD; Qiang Zhang and Jonathan Harris, Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA; Christina S. Kong and Quynh-Thu Le, Stanford University, Stanford; Richard C. Jordan, University of California at San Francisco, San Francisco, CA; Paul M. Harari, University of Wisconsin Carbone Cancer Center, Madison; Dian Wang, Medical College of Wisconsin, Milwaukee, WI; Kevin P. Redmond, University of Cincinnati, Cincinnati; Maura L. Gillison, Ohio State University, Columbus, OH; George Shenouda, McGill University Health Centre, Montreal, Quebec, Canada; Andy Trotti, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; and David Raben, University of Colorado, Denver, CO.
Abstract
PURPOSE: Although p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been well established in cancer of the oral cavity, hypopharynx, or larynx, collectively referred as non-OPSCC, where HPV infection is less common than in the oropharynx. PATIENTS AND METHODS: p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129, 0234, and 0522 studies were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). Hazard ratios from Cox models were expressed as positive or negative, stratified by trial, and adjusted for clinical characteristics. RESULTS:p16 expression was positive in 14.1% (12 of 85), 24.2% (23 of 95), and 19.0% (27 of 142) and HPV ISH was positive in 6.5% (six of 93), 14.6% (15 of 103), and 6.9% (seven of 101) of non-OPSCCs from RTOG 0129, 0234, and 0522 studies, respectively. Hazard ratios for p16 expression were 0.63 (95% CI, 0.42 to 0.95; P = .03) and 0.56 (95% CI, 0.35 to 0.89; P = .01) for progression-free (PFS) and overall survival (OS), respectively. Comparing OPSCC and non-OPSCC, patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC, but patients with p16-negative OPSCC and non-OPSCC have similar outcomes. CONCLUSION: Similar to results in patients with OPSCC, patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC, and HPV may also have a role in outcome in a subset of non-OPSCC. However, further development of a p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting.
RCT Entities:
PURPOSE: Although p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been well established in cancer of the oral cavity, hypopharynx, or larynx, collectively referred as non-OPSCC, where HPV infection is less common than in the oropharynx. PATIENTS AND METHODS: p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129, 0234, and 0522 studies were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). Hazard ratios from Cox models were expressed as positive or negative, stratified by trial, and adjusted for clinical characteristics. RESULTS:p16 expression was positive in 14.1% (12 of 85), 24.2% (23 of 95), and 19.0% (27 of 142) and HPV ISH was positive in 6.5% (six of 93), 14.6% (15 of 103), and 6.9% (seven of 101) of non-OPSCCs from RTOG 0129, 0234, and 0522 studies, respectively. Hazard ratios for p16 expression were 0.63 (95% CI, 0.42 to 0.95; P = .03) and 0.56 (95% CI, 0.35 to 0.89; P = .01) for progression-free (PFS) and overall survival (OS), respectively. Comparing OPSCC and non-OPSCC, patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC, but patients with p16-negative OPSCC and non-OPSCC have similar outcomes. CONCLUSION: Similar to results in patients with OPSCC, patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC, and HPV may also have a role in outcome in a subset of non-OPSCC. However, further development of a p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting.
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