A comprehensive evaluation of human papillomavirus positive status and p16INK4a overexpression as a prognostic biomarker in head and neck squamous cell carcinoma.
A comprehensive evaluation of human papillomavirus positive status and p16INK4a overexpression as a prognostic biomarker in head and neck squamous cell carcinoma.
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DOI：
10.3892/ijo.2014.2440
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发表时间：
2014-07
影响因子：
5.2
通讯作者：
Suzuki M
中科院分区：
文献类型：
--
作者：
Deng Z;Hasegawa M;Aoki K;Matayoshi S;Kiyuna A;Yamashita Y;Uehara T;Agena S;Maeda H;Xie M;Suzuki M
患有人乳头瘤病毒（HPV）感染的头颈部鳞状细胞癌（HNSCC）患者比未感染HPV的患者预后更好。尽管p16 INK 4a表达被用作HPV感染的替代标志物，但关于p16 INK 4a是否可靠地指示HPV感染存在争议。为了评价p16 INK 4a表达对确定HPV感染的准确性以及HPV感染和p16 INK 4a表达对HNSCC生存，特别是口咽鳞状细胞癌（OPSCC）生存的预后价值，我们采用聚合酶链反应和免疫组化方法分析了150例新鲜冷冻HNSCC标本的HPV DNA、E6/E7 mRNA和p16 INK 4a表达。根据p16 INK 4a阳性细胞的百分比，将p16 INK 4a表达从0到4评分，过表达定义为>40%阳性细胞。在检测的150个肿瘤样本中，10个肿瘤位于鼻咽部，53个位于口咽部，39个位于下咽部，24个位于喉部，24个位于口腔。47例（31.3%）标本中检测到HPV DNA，但只有21例同时显示HPV mRNA表达。p16 INK 4a表达与HPV DNA存在之间以及p16 INK 4a表达与HPV mRNA表达之间的评分者间一致性较低，但HPV DNA状态与p16 INK 4a过表达和HPV mRNA表达之间的组合之间的一致性良好。HPV DNA阳性的OPSCC患者的3年无复发生存率显著高于HPV DNA阴性的OPSCC患者（P=0.008），过表达p16 INK 4a的OPSCC患者的3年无复发生存率显著高于不过表达p16 INK 4a的OPSCC患者（P=0.034）。多因素分析显示，T1-3分期、HPV DNA阳性和p16 INK 4a过表达联合预测无复发生存率显著更好。与单独检测HPV DNA状态或p16 INK 4a阳性状态相比，该联合检测是HNSCC中活动性HPV感染更准确的标志物，并为检测和确定HPV相关HNSCC的预后提供了有用和可靠的方法。
Head and neck squamous cell carcinoma (HNSCC) patients with human papillomavirus (HPV) infection have better prognosis than those without HPV infection. Although p16INK4a expression is used as a surrogate marker for HPV infection, there is controversy as to whether p16INK4a reliably indicates HPV infection. Here, to evaluate the accuracy of p16INK4a expression for determining HPV infection and the prognostic value of HPV infection and p16INK4a expression for HNSCC survival, especially oropharyngeal squamous cell carcinoma (OPSCC) survival, 150 fresh-frozen HNSCC samples were analyzed for HPV DNA, E6/E7 mRNA and p16INK4a expression by polymerase chain reaction and immunohistochemistry. p16INK4a expression was scored from 0 to 4 according to the percentage of p16INK4a-positive cells, with overexpression defined as >40% positive cells. Of the 150 tumor samples tested, 10 tumors were nasopharyngeal, 53 oropharyngeal, 39 hypopharyngeal, 24 laryngeal and 24 were located in the oral cavity. HPV DNA was detected in 47 (31.3%) samples, but only 21 also exhibited HPV mRNA expression. Inter-rater agreement was low between p16INK4a expression and HPV DNA presence and between p16INK4a expression and HPV mRNA expression, but was good between the combination of HPV DNA status and p16INK4a overexpression and HPV mRNA expression. Three-year recurrence-free survival was significantly higher for OPSCC patients who were HPV DNA-positive than for OPSCC patients who were HPV DNA-negative (P=0.008) and for OPSCC patients over-expressing p16INK4a than for without overexpressing p16INK4a (P=0.034). Multivariate analysis revealed that T1-3 stage and the combination of HPV DNA positivity and p16INK4a overexpression predicted significantly better recurrence-free survival. This combination is a more accurate marker for active HPV infection in HNSCC than HPV DNA status or general p16INK4a-positive status alone and offers a useful and reliable method for detecting and determining the prognosis of HPV-related HNSCC.
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影响因子：
6.4
作者：
Ragin, Camille C. R.;Taioli, Emanuela
通讯作者：
Taioli, Emanuela
影响因子：
6.4
作者：
Hafkamp, Harriet C.;Manni, J. J.;Speel, Ernst-Jan M.
通讯作者：
Speel, Ernst-Jan M.
影响因子：
45.3
作者：
Lassen, Pernille;Eriksen, Jesper G.;Overgaard, Jens
通讯作者：
Overgaard, Jens
影响因子：
10.3
作者：
Fakhry, Carole;Westra, William H.;Gillison, Maura L.
通讯作者：
Gillison, Maura L.
影响因子：
1.9
作者：
LANDIS, JR;KOCH, GG
通讯作者：
KOCH, GG