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p16 expression as a human papillomavirus (HPV)-independent prognostic biomarker in non-oropharyngeal squamous cell carcinoma (non-OPSCC).
J Clin Oncol 31, 2013 (suppl; abstr 6007)
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: p16 is an important tumor suppressor and cell cycle regulator that is commonly lost in HPV-negative (-) and upregulated in HPV-positive (+) OPSCC. While the role of p16 expression in OPSCC as a surrogate marker of HPV infection and its association with prognosis are well established, its significance has not been studied in non-OPSCC including oral cavity, hypopharynx and larynx, where HPV infection is rare. We hypothesize that p16 expression is a prognostic biomarker of favorable outcome (progression-free and overall survival) in non-OPSCC. Methods: p16 expression in non-OPSCC from RTOG 0129, 0234 and 0522 was determined by immunohistochemistry (p16 mouse monoclonal antibody, prediluted, MTM-CINtech, 9518) and considered positive if >70% of the tumor cells demonstrated diffuse staining. The high risk HPV status in non-OPSCC from RTOG 0129 and 0522 was determined by in situ hybridization using a cocktail probe including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 66. Hazard ratios from Cox models were expressed as positive/negative, stratified by trial, and adjusted for age, gender, T, and N stage. Results: p16 expression was positive in 14.1% (12/85), 24.2% (23/95) and 19.0% (27/142) of non-OPSCC from RTOG 0129, RTOG 0234, and RTOG 0522, respectively. HPV ISH was positive in 6.5% (6/93) and 6.9% (7/101) of non-OPSCC from RTOG 0129 and RTOG 0522, respectively. There was moderate agreement between p16 and HPV status (kappa=0.53). The hazard ratios for p16 expression are 0.63 (p=0.03) and 0.56 (p=0.01) for PFS and OS, respectively. In 0522, there was no interaction between p16 status and two treatment arms (RT+cisplatin+/-cetuximab). In comparison of OPSCC and non-OPSCC, patients with p16(+) OPSCC have better PFS and OS than patients with p16(+) non-OPSCC, but patients with p16(-) OPSCC and non-OPSCC have similar outcomes. Conclusions: Similar to results in patients with OPSCC, patients with p16(+) non-OPSCC have better outcomes than patients with p16(-); however, the differential appears smaller than has been observed in HPV(+) OPSCC. Further studies are warranted to delineate the role of p16 expression as a prognostic biomarker in non-OPSCC and OPSCC. Clinical trial information: NCT00265941, NCT00047008, NCT00084318.
Abstracts by C. H. Chung:
Analysis of the effect of p16 and tobacco pack-years (p-y) on overall (OS) and progression-free survival (PFS) for patients with oropharynx cancer (OPC) in Radiation Therapy Oncology Group (RTOG) protocol 9003.
Association of high Gli1 expression with poor survival in head and neck cancer patients treated with radiation therapy (RTOG 9003).