p16 Protein Expression and Human Papillomavirus Status As Prognostic Biomarkers of Nonoropharyngeal Head and Neck Squamous Cell Carcinoma
p16 Protein Expression and Human Papillomavirus Status As Prognostic Biomarkers of Nonoropharyngeal Head and Neck Squamous Cell Carcinoma
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DOI：
10.1200/jco.2013.54.5228
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发表时间：
2014-12-10
影响因子：
45.3
通讯作者：
Quynh-Thu Le
中科院分区：
文献类型：
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作者：
Chung, Christine H.;Zhang, Qiang;Quynh-Thu Le
虽然p16蛋白表达是人类乳头瘤病毒(HPV)感染的替代标志物，被认为是口咽鳞状细胞癌(OPSCC)的预后标志物，但其在口腔、下咽或喉癌(统称为非OPSCC)中的患病率和意义尚未得到很好的证实。结果来自RTOG 0129、0234和0522研究的非OPSCC中，sp16的阳性表达分别为14.1%(12/85)、24.2%(23/95)和19.0%(27/142)，HPV ISH分别为6.5%(6/93)、14.6%(15/103)和6.9%(7/101)。无进展(PFS)和总生存期(OS)p16表达的风险比分别为0.63(95%CI，0.42~0.95；P=0.03)和0.56(95%CI，0.35~0.89；P=0.01)。与非OPSCC相比，p16阳性的OPSCC患者的PFS和OS明显优于p16阳性的非OPSCC患者，而p16阴性的OPSCC患者和非OPSCC患者的预后相似。结论与OPSCC患者的结果相似，p16阴性的非OPSCC患者的预后比p16阳性的非OPSCC患者差，HPV可能也对非OPSCC患者的预后有影响。然而，在广泛应用于临床之前，在非OPSCC中进一步开发p16 IHC评分系统和改进HPV检测方法是必要的。(C)美国临床肿瘤学会2014年
PurposeAlthough 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 Methodsp16 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.Resultsp16 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.ConclusionSimilar 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. (C) 2014 by American Society of Clinical Oncology