Oropharyngeal Squamous Cell Carcinoma With Discordant p16 and HPV mRNA Results

Oropharyngeal Squamous Cell Carcinoma With Discordant p16 and HPV mRNA Results
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p16 和 HPV mRNA 结果不一致的口咽鳞状细胞癌

DOI:
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发表时间:
2021
影响因子:
5.6
通讯作者:
J. Lewis
J. Lewis
中科院分区:
医学1区
文献类型:
--
作者:
J. Shinn;Seth J. Davis;Krystle A. Lang;S. Rohde;Xiao;Ping Liu;W. Dupont;D. Plummer;W. Thorstad;R. Chernock;M. Mehrad;J. Lewis

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早期研究估计,5%至10%的口咽鳞状细胞癌过表达p16,但与转录活性高风险的人乳头瘤病毒(HPV)无关。HPV检测结果不一致的患者可能会经历与传统预期不同的临床结果。为了记录p16和HPV信使核糖核酸的阳性率,用不一致的检测来描述患者的特征,并确定可能需要在p16IHC后选择使用HPV特异性检测的特征,我们对用逆转录聚合酶链式反应检测p16IHC和HPV信使核糖核酸的口咽鳞状细胞癌患者进行了多机构的回顾。在467例患者中,大多数为T1或T2肿瘤(71%),82%为p16阳性,84%为HPV mRNA阳性。总体而言,大多数肿瘤是非角化性的(378,81%),这与p16和HPV阳性(分别为93%和95%)密切相关。总体上,81%的患者为双阳性,14%为双阴性,4.9%为不一致(p16阴性/HPV mRNA阳性占3.4%,p16阳性/HPV mRNA阴性占1.5%)。尽管在对无病生存率和总体生存率的多因素分析中,这些不一致的患者组的存活率在两个一致的组之间下降,但没有发现不一致的患者具有统计学上显著的差异。当p16结果与形态不匹配时,或当p16结果不明确时,通过应用HPV mRNA检测对患者进行重新分类,比单独应用p16或HPV mRNA检测略有改善预后。测试不一致的患者表现出与测试一致的患者存活率差异的边缘显着趋势。单独评估时,p16阴性但HPV mRNA阳性的患者预后更接近双阳性患者,而p16阳性但HPV mRNA阴性的患者预后更接近双阴性患者。我们建议了一种算法,在p16状态与肿瘤形态不一致的患者中进行确认性HPV mRNA检测。这捕捉到了大多数不和谐的患者,并改善了预测,尽管是温和的。
Early studies estimate that 5% to 10% of oropharyngeal squamous cell carcinomas overexpress p16 but are unassociated with transcriptionally-active high-risk human papillomavirus (HPV). Patients with discordant HPV testing may experience clinical outcomes that differ from traditional expectations. To document the rate of p16 and HPV mRNA positivity, characterize patients with discordant testing, and identify features that may warrant selective use of HPV-specific testing after p16 IHC, a multi-institutional, retrospective review of oropharyngeal squamous cell carcinoma patients with p16 IHC and HPV mRNA testing by reverse transcriptase polymerase chain reaction was performed. Of the 467 patients, most had T1 or T2 tumors (71%), 82% were p16 positive, and 84% were HPV mRNA positive. Overall, most tumors were nonkeratinizing (378, 81%), which was strongly associated with p16 and HPV positivity (93% and 95%, respectively). Overall, 81% of patients were double positive, 14% double negative, and 4.9% discordant (3.4% p16 negative/HPV mRNA positive and 1.5% p16 positive/HPV mRNA negative). The survival rates of these discordant patient groups fell squarely between the 2 concordant groups, although in multivariate analysis for both disease-free survival and overall survival, discordant patients were not found to have statistically significantly different outcomes. Reclassifying patients by applying HPV mRNA testing when p16 results and morphology do not match, or when p16 results are equivocal, improved prognostication slightly over p16 or HPV mRNA testing alone. Patients with discordant testing demonstrate a borderline significant trend toward survival differences from those with concordant tests. When evaluated independently, patients who were p16 negative but HPV mRNA positive had a prognosis somewhat closer to double-positive patients, while those who were p16 positive, but HPV mRNA negative had a prognosis closer to that of double-negative patients. We suggest an algorithm whereby confirmatory HPV mRNA testing is performed in patients where p16 status is not consistent with tumor morphology. This captures a majority of discordant patients and improves, albeit modestly, the prognostication.
DOI: 10.1200/jco.2010.29.2904
发表时间: 2010-09-20
影响因子: 45.3
作者:
Rischin, Danny;Young, Richard J.;McArthur, Grant A.
通讯作者: McArthur, Grant A.