Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.
Cancer Cytopathol. 2019 Oct;127(10):632-642. doi: 10.1002/cncy.22178. Epub 2019 Sep 11.
Many patients with human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HPV-HNSCC) initially present with cervical lymph node metastases. Although p16 immunohistochemistry (IHC) is the most commonly used surrogate marker for HPV, however criteria in cytologic material are not well established. The objective of this study was to better characterize p16 IHC in cell blocks of metastatic HPV-HNSCC, and to evaluate the performance of HPV RNA in situ hybridization (RNA ISH).
p16 IHC was performed on cell blocks from 97 metastatic HPV-HNSCC fine-needle aspiration specimens with HPV status confirmed by DNA or RNA ISH or polymerase chain reaction (PCR). Tumor cellularity (<100 cells, 100-500 cells, and >500 cells) and quality (presence of cell clusters, necrosis) were recorded. p16 staining intensity and extent (1%-9%, 10%-69%, and ≥70%) were scored. In addition, RNA ISH was performed on 38 PCR-positive cases.
p16 IHC was positive in 90 of 97 cases (93%), demonstrating variable patterns. p16 staining was found to be moderate to strong in 69 cases, with 37 cases (38%) demonstrating positivity in ≥70% of tumor cells. Weak staining occurred in 21 cases (22%) and 7 cases (7%) were negative. Of the 60 cases with weak and/or absent expression or staining in <70% of cells, 30 cases (50%) had <100 tumor cells, 12 (20%) lacked cell clusters, and 19 cases (32%) had extensive necrosis. RNA ISH was positive in 37 of 38 cases (97%) that were HPV positive by PCR.
p16 is heterogeneous in cell blocks of metastatic HPV-HNSCC, suggesting that any p16 positivity should prompt confirmatory HPV studies. RNA ISH appears to demonstrate high sensitivity, and laboratories even may consider using RNA ISH as a first-line HPV test in cytologic specimens.
许多人乳头瘤病毒（HPV）相关的头颈部鳞状细胞癌（HPV-HNSCC）患者最初表现为颈部淋巴结转移。虽然 p16 免疫组化（IHC）是最常用的 HPV 替代标志物，但细胞学标本中的标准尚未得到很好的建立。本研究的目的是更好地描述转移性 HPV-HNSCC 细胞块中的 p16 IHC，并评估 HPV RNA 原位杂交（RNA ISH）的性能。
对 97 例转移性 HPV-HNSCC 细针抽吸标本的细胞块进行 p16 IHC 检测，HPV 状态通过 DNA 或 RNA ISH 或聚合酶链反应（PCR）确认。记录肿瘤细胞数量（<100 个细胞、100-500 个细胞和>500 个细胞）和质量（细胞簇存在、坏死）。p16 染色强度和范围（1%-9%、10%-69%和≥70%）进行评分。此外，对 38 例 PCR 阳性病例进行 RNA ISH。
97 例（93%）中 p16 IHC 阳性，表现出不同的模式。p16 染色强度为中度至强，其中 69 例（38%）≥70%的肿瘤细胞呈阳性。21 例（22%）呈弱阳性，7 例（7%）阴性。在 60 例<70%的细胞呈弱表达或无表达的病例中，30 例（50%）肿瘤细胞<100 个，12 例（20%）缺乏细胞簇，19 例（32%）广泛坏死。38 例 HPV 阳性的病例中，37 例（97%）的 RNA ISH 阳性。
转移性 HPV-HNSCC 细胞块中的 p16 呈异质性，表明任何 p16 阳性均应提示进行 HPV 确认研究。RNA ISH 显示出较高的敏感性，实验室甚至可以考虑在细胞学标本中使用 RNA ISH 作为 HPV 检测的一线方法。
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