Evaluation for High-risk HPV in Squamous Cell Carcinomas and Precursor Lesions Arising in the Conjunctiva and Lacrimal Sac
Evaluation for High-risk HPV in Squamous Cell Carcinomas and Precursor Lesions Arising in the Conjunctiva and Lacrimal Sac
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DOI：
10.1097/pas.0000000000000581
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发表时间：
2016-04-01
影响因子：
5.6
通讯作者：
Faquin, William C.
中科院分区：
文献类型：
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作者：
Afrogheh, Amir H.;Jakobiec, Frederick A.;Faquin, William C.
高危型人乳头状瘤病毒（HR-HPV）是口咽鳞状细胞癌（SCC）的一种公认的致病因子。此外，HR-HPV偶尔被报道存在于结膜和泪囊的发育不良和恶性病变中，尽管其在眼周SCC中的总体发病率和病因学作用存在争议。选择14年（2000年至2014年）期间诊断的2个眼周部位（结膜和泪囊）的52例浸润性SCC（I-SCC）和原位SCC（SCCIS）合并病例的连续手术样本进行评价，并记录相关患者特征。进行p16免疫组织化学作为筛选试验。所有p16阳性病例进一步评估HR-HPV使用DNA原位杂交（DNA ISH），并通过聚合酶链反应（PCR）的子集进行了分析。在43例眼表鳞状细胞瘤（OSSNs）中，30%（n=13; 8例SCCIS和5例I-SCC病例）为HR-HPV阳性。HPV阳性OSSN发生在8名男性和5名女性中，平均年龄为60岁（范围，39至94岁）。PCR检测所有结膜病例均检出HPV 16型。所有5例结膜I-SCC均为非角化（n=4）或部分角化（n=1），并通过简单切除进行治疗。相反，HPV阴性结膜I-SCC主要是角化性的（11例角化性和2例非角化性）。9例泪囊I型鳞状细胞癌（LSSCC）中，6例（66.7%）经p16和DNA原位杂交检测为HR-HPV阳性，HPV亚型为HPV-16（n=5）和HPV-58（n=1）。此外，2例p16阳性但DNA原位杂交结果阴性的病例经PCR检测为HR-HPV阳性（HPV-16和HPV-33），表明HR-HPV在LSSCC中的阳性率可能高达89%（n=8）。HR-HPV阳性LSSCC的合并组见于4名男性和4名女性，平均年龄为60岁（范围，34至71岁）。8例HPV阳性LSSCC中7例（87.5%）组织形态学表现为非角化或部分角化，1例（12.5%）以角化为主。HR-HPV在30%的OSSN和至少66.7%的LSSCC中的存在表明HR-HPV在这些部位的病因作用的可能性。
High-risk human papilloma virus (HR-HPV) is a well-established causative agent of oropharyngeal squamous cell carcinoma (SCC). In addition, HR-HPV has occasionally been reported to be present in dysplastic and malignant lesions of the conjunctiva and lacrimal sac, although its overall incidence and etiological role in periocular SCC are controversial. Sequential surgical samples of 52 combined cases of invasive SCC (I-SCC) and SCC in situ (SCCIS) from 2 periocular sites (conjunctiva and lacrimal sac) diagnosed over a 14-year period (2000 to 2014) were selected for evaluation, and relevant patient characteristics were documented. p16 immunohistochemistry was performed as a screening test. All p16-positive cases were further evaluated for HR-HPV using DNA in situ hybridization (DNA ISH), and a subset was also analyzed by polymerase chain reaction (PCR). Of 43 ocular surface squamous neoplasias (OSSNs), 30% (n=13; 8 SCCIS and 5 I-SCC cases) were positive for HR-HPV. HPV-positive OSSNs occurred in 8 men and 5 women with a mean age of 60 years (range, 39 to 94 y). HPV type-16 was detected in all conjunctival cases evaluated by PCR. All 5 conjunctival I-SCCs were nonkeratinizing (n=4) or partially keratinizing (n=1) and managed by simple excision. In contrast, HPV-negative conjunctival I-SCCs were predominantly keratinizing (11 keratinizing and 2 nonkeratinizing). Of 9 lacrimal sac I-SCCs (LSSCCs), 66.7% (n=6) were positive for HR-HPV by p16 and DNA ISH; HPV subtypes were HPV-16 (n=5) and HPV-58 (n=1). In addition, 2 p16-positive cases with negative DNA ISH results were HR-HPV positive (HPV-16 and HPV-33) when evaluated by PCR, suggesting that the rate of HR-HPV positivity among the LSSCCs may be as high as 89% (n=8). The combined group of HR-HPV-positive LSSCCs was seen in 4 men and 4 women with a mean age of 60 years (range, 34 to 71 y). Seven of the 8 HPV-positive LSSCCs (87.5%) had a nonkeratinizing or partially keratinizing histomorphology, whereas 1 case (12.5%) was predominantly keratinizing. The presence of HR-HPV in 30% of OSSNs and at least 66.7% of LSSCCs suggests the possibility of an etiologic role for HR-HPV at these sites.