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转录活跃型人乳头瘤病毒状况与头颈部鳞状细胞癌的临床和分子特征的相关性。

Correlation of transcriptionally active human papillomavirus status with the clinical and molecular profiles of head and neck squamous cell carcinomas.

机构信息

Mahimkar Lab, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India.

Homi Bhabha National Institute, Mumbai, India.

出版信息

Head Neck. 2021 Jul;43(7):2032-2044. doi: 10.1002/hed.26676. Epub 2021 Mar 10.

DOI:10.1002/hed.26676

PMID:33751711

Abstract

BACKGROUND

To examine the molecular profiles of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinomas (HNSCCs), expression of epidermal growth factor receptor (EGFR), phospho-EGFR dimers, hypoxia markers, and cancer stem cell markers were evaluated.

METHODS

HPV-status was confirmed using RNA-ISH. Immunohistochemical data of biomarker expression levels were analyzed using the Mann-Whitney U test. The clinical outcomes and biomarker expression in the HPV-positive (n = 25), matched HPV-negative (n = 49), and p16-positive/HPV-negative (n = 20) subgroups were comparatively analyzed.

RESULTS

HPV was detected in 25 (5.8%) cases and was significantly associated with favorable outcomes. HPV-positive tumors exhibited lower membrane expression of EGFR, pEGFRY1068, pEGFRY1173, CD44, CD44v6, and CD98hc than HPV-negative and p16-positive tumors. The expression of HIF1α, CA9, ALDH1A1, and SOX2 was not significantly associated with HPV-status. The clinical outcomes and biomarker expression levels were similar between the HPV-negative and p16-positive HNSCC.

CONCLUSION

HPV-positive HNSCC exhibited distinct molecular profile compared to HPV-negative and p16-positive HNSCC. The clinical and molecular profiles were similar between p16-positive and HPV-negative subgroups.

摘要

背景

为了研究人乳头瘤病毒（HPV）阳性和 HPV 阴性头颈部鳞状细胞癌（HNSCC）的分子谱，评估了表皮生长因子受体（EGFR）、磷酸化 EGFR 二聚体、缺氧标志物和癌症干细胞标志物的表达。

方法

使用 RNA-ISH 确认 HPV 状态。使用 Mann-Whitney U 检验分析生物标志物表达水平的免疫组织化学数据。比较 HPV 阳性（n=25）、匹配的 HPV 阴性（n=49）和 p16 阳性/HPV 阴性（n=20）亚组的临床结果和生物标志物表达。

结果

在 25 例（5.8%）病例中检测到 HPV，与良好的预后显著相关。HPV 阳性肿瘤的 EGFR、pEGFRY1068、pEGFRY1173、CD44、CD44v6 和 CD98hc 的膜表达明显低于 HPV 阴性和 p16 阳性肿瘤。HIF1α、CA9、ALDH1A1 和 SOX2 的表达与 HPV 状态无明显相关性。HPV 阴性和 p16 阳性 HNSCC 的临床结局和生物标志物表达水平相似。