Tissue distribution of human papillomavirus 16 DNA integration in patients with tonsillar carcinoma
Tissue distribution of human papillomavirus 16 DNA integration in patients with tonsillar carcinoma
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DOI：
10.1158/1078-0432.ccr-05-0587
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发表时间：
2005-08-15
影响因子：
11.5
通讯作者：
Westra, WH
中科院分区：
文献类型：
--
作者：
Begum, S;Cao, DF;Westra, WH
目的：人乳头瘤病毒16型(HPV-16)是头颈部鳞状细胞癌(HNSCC)的致病因子。本研究旨在了解HPV病毒整合在上呼吸道肿瘤发生过程中的分布和时间。实验设计：由176例HNSCC患者组成的组织阵列。用HPV-16原位杂交和p16免疫组织化学方法对芯片进行鉴定。选择接受双侧扁桃体切除术的HPV阳性扁桃体癌患者进行更完整的病毒整合图谱。结果：在176例扁桃体癌患者中，原位杂交法检测到38例HPV-16，占22%。当按起源部位分层时，口咽部45例肿瘤中37例检出HPV-16，而非口咽部位仅1例(82%对0.8%，P<；0.00001)。P16表达与HPV-1感染有关：38例HPV阳性肿瘤中31例p16表达，而在138例HPV阴性肿瘤中只有9例p16表达(82%对6%，P<；0.00001)。在双侧扁桃体切片中，杂交信号仅限于浸润性癌及其伴发的不典型增生。结论：HPV-16与口咽癌的发生密切相关，整合与肿瘤的发生密切相关。病毒整合并不是发生在正常扁桃体上皮的野生性改变。P16的表达定位于HPV阳性的癌症，是扁桃体隐窝的特化上皮所固有的。对于风险评估、早期癌症检测和疾病监测，HPV-16整合的证据可能代表着一个有意义的发现，而高p16表达本身可能不是。
Purpose: Human papillomavirus 16 (HPV-16) has been implicated as a causative agent in a subset of head and neck squamous cell carcinomas (HNSCC). This study was undertaken to discern the distribution and timing of HPV viral integration during tumorigenesis of the upper respiratory tract.Experimental Design: A tissue array was assembled from a consecutive group of 176 patients with HNSCCs. The array was evaluated by HPV-1 6 in situ hybridization and p16 immunohistochemistry. Patients with HPV-positive tonsillar cancers who had undergone bilateral tonsillectomies were selected for more complete mapping of viral integration.Results: HPV-1 6 was detected in 38 of the 176 (22%) cases by in situ hybridization. When stratified by site of origin, HPV-16 was detected in 37 of 45 cancers arising from the oropharynx but in only 1 of 131 tumors arising from nonoropharyngeal sites (82% versus 0.8%, P < 0.00001). P16 expression was associated with the presence of HPV-1 6: 31 of 38 HPV-positive tumors exhibited p16 expression, whereas only 9 of the 138 HPV-negative tumors were p16-positive (82% versus 6%, P < 0.00001). In the bilateral tonsil sections, hybridization signals were strictly limited to the invasive cancers and associated dysplasias. P16 staining was widely distributed throughout the nonneoplastic crypt epithelium of individuals with and without tonsillar cancer.Conclusions: HPV-1 6 is strongly associated with carcinomas arising from the oropharynx, and integration is tightly coupled to the neoplastic process. Viral integration does not occur as a field alteration throughout normal tonsillar epithelium. P16 expression localizes to HPV-positive cancers, and is intrinsic to the specialized epithelium of the tonsillar crypts. For risk assessment, early cancer detection and disease surveillance, evidence of HPV-16 integration may represent a meaningful finding, whereas high p16 expression, by itself, may not.