Detection of human papillomavirus-16 in fine-needle aspirates to determine tumor origin in patients with metastatic squamous cell carcinoma of the head and neck
Detection of human papillomavirus-16 in fine-needle aspirates to determine tumor origin in patients with metastatic squamous cell carcinoma of the head and neck
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DOI：
10.1158/1078-0432.ccr-06-1690
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发表时间：
2007-02-15
影响因子：
11.5
通讯作者：
Westra, William H.
中科院分区：
文献类型：
--
作者：
Begum, Shahnaz;Gillison, Maura L.;Westra, William H.
目的：头颈部鳞状细胞癌(HNSCC)患者临床上常伴有区域淋巴结转移。颈部肿块的细针抽吸常规用于确定转移癌的存在，进而开始随后的检查以确定肿瘤起源的位置。人类乳头瘤病毒(HPV)16是口咽部HNSCCs的重要病原体，但对非口咽部位的肿瘤则不是如此。因此，HPV16的检测为定位HNSCC的一个重要亚群提供了一种策略，但这种方法还没有应用于细针吸取标本。实验设计：我们对77个连续的被诊断为转移性鳞状细胞癌的颈部肿块进行了HPV16的原位杂交。P16蛋白的过度表达可作为HPV相关性HNSCC的替代标志物。结果：77例吸入物中13例检测到HPV16。按起源部位划分，在19例口咽转移癌中有10例检出HPV16型，而在46例其他部位的转移癌中均未检出HPV16型(53%对0%；P<；0.0001)。在10例隐匿性原发灶中，有3例P16阳性表达：13例HPV16阳性转移瘤中12例阳性，而62例HPV16阴性转移瘤中仅4例阳性(92%对6%；P<；0.0001)。P16的表达还与肿瘤起源有关：19例口咽转移癌中13例p16阳性，而46例非口咽转移癌中仅11例p16阳性(68%vs2%；P<；0.0001)。结论：从转移性鼻咽癌患者颈部抽吸的肿瘤细胞中可以确定HPV16状态。它的存在是口咽部起源的可靠指标。
Purpose: Patients with head and neck squamous cell carcinoma (HNSCC) often clinically present with metastases to regional lymph nodes. Fine-needle aspiration of neck masses is routinely used to establish the presence of metastatic carcinoma and in turn to initiate a subsequent workup to determine the site of tumor origin. Human papillomavirus (HPV) 16 is an important etiologic agent for HNSCCs that arise from the oropharynx but less so for tumors from non-oropharyngeal sites. HPV16 detection thus provides a strategy for localizing an important subset of HNSCCs, but this approach has not been applied to fine-needle aspiration specimens.Experimental Design: We did in situ hybridization for HPV16 on 77 consecutive aspirated neck masses diagnosed as metastatic squamous cell carcinoma. P16 immunohistochemistry was also done because p16 overexpression may serve as a surrogate marker of HPV-associated HNSCC.Results: HPV16 was detected in 13 of the 77 (17%) aspirates. By site of origin, HPV16 was detected in 10 of 19 metastases from the oropharynx but in none of 46 metastases from other sites (53% versus 0%; P < 0.0001). HPV16 was not detected in 2 branchial cleft cysts misdiagnosed as metastatic squamous cell carcinoma, but it was detected in 3 of 10 metastases from occult primary tumors, P16 expression was associated with the presence of HPV16: 12 of 13 HPV16-positive metastases exhibited p16 expression, whereas only 4 of 62 HPV16-negative metastases were p16 positive (92% versus 6%; P < 0.0001). P16 expression also correlated with site of tumor origin: 13 of 19 oropharyngeal metastases were p16 positive, whereas only 11 of 46 non-oropharyngeal metastases was p16 positive (68% versus 2%; P < 0.0001).Conclusions: HPV16 status can be determined in tumor cells aspirated from the necks of patients with metastatic HNSCC. Its presence is a reliable indicator of origin from the oropharynx.