Begum Shahnaz, Gillison Maura L, Nicol Theresa L, Westra William H
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231-2410, USA.
Clin Cancer Res. 2007 Feb 15;13(4):1186-91. doi: 10.1158/1078-0432.CCR-06-1690.
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.
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.
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 1 of 46 non-oropharyngeal metastases was p16 positive (68% versus 2%; P < 0.0001).
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.
头颈部鳞状细胞癌（HNSCC）患者临床上常出现区域淋巴结转移。颈部肿块细针穿刺活检通常用于确定转移性癌的存在，进而启动后续检查以确定肿瘤起源部位。人乳头瘤病毒（HPV）16是口咽来源的HNSCC的重要病因，但对于非口咽部位的肿瘤而言，其作用较小。因此，HPV16检测为定位HNSCC的一个重要亚组提供了一种策略，但该方法尚未应用于细针穿刺活检标本。
我们对77例连续的诊断为转移性鳞状细胞癌的颈部穿刺肿块进行了HPV16原位杂交检测。同时进行了p16免疫组化检测，因为p16过表达可能作为HPV相关HNSCC的替代标志物。
77例穿刺物中有13例（17%）检测到HPV16。按肿瘤起源部位，19例口咽转移灶中有10例检测到HPV16，而46例其他部位转移灶中均未检测到（53%对0%；P<0.0001）。2例误诊为转移性鳞状细胞癌的鳃裂囊肿未检测到HPV16，但10例隐匿性原发肿瘤转移灶中有3例检测到。p16表达与HPV16的存在相关：13例HPV16阳性转移灶中有12例表现为p16表达，而62例HPV16阴性转移灶中仅有4例p16阳性（92%对6%；P<0.0001）。p16表达也与肿瘤起源部位相关：19例口咽转移灶中有13例p16阳性，而46例非口咽转移灶中仅有1例p16阳性（68%对2%；P<0.0001）。
转移性HNSCC患者颈部穿刺的肿瘤细胞中可确定HPV16状态。其存在是口咽起源的可靠指标。
