Department of Otolaryngology/Head-Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands; Department of Maxillofacial Surgery/Oral Pathology, VU University Medical Center/Academic Centre for Dentistry, Amsterdam, The Netherlands.
Eur J Cancer. 2014 Mar;50(4):765-73. doi: 10.1016/j.ejca.2013.11.010. Epub 2013 Dec 4.
Several hypotheses have been proposed to explain the relatively good prognosis of patients with a human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) and one of these is a higher sensitivity to (chemo)radiation. Previous studies have suggested that treatment failure in OPSCC patients is caused by resistance of cancer stem cells (CSCs). The purpose of this study was to evaluate the association between the number of CSCs and prognosis in HPV-positive OPSCC patients.
All OPSCC patients (n=711) treated between 2000 and 2006 in two Dutch university hospitals were included. Presence of HPV in a tumour tissue specimen was tested by p16-immunostaining followed by HPV DNA GP5+/6+polymerase chain reaction (PCR). The presence and intensity of tumour CSC markers CD44 and CD98 were determined by immunohistochemistry and semiquantitative scoring was performed. Overall survival (OS) and progression-free survival (PFS) rates were compared between patients with low and high CD44/CD98 expression in relation to HPV status.
HPV-positive tumours showed a lower percentage of cells with CD44 and CD98 expression than HPV-negative tumours (p<0.001, χ(2)-test). Within the group of patients with HPV-positive OPSCC, a high percentage of CD98-positive tumour cells was associated with a significantly worse 5-year OS and PFS (OS: 36.4% and PFS: 27.3%) compared to patients with a low percentage of CD98-positive cells (OS: 71.9% and PFS: 70.5%, respectively) (p<0.001).
HPV-positive OPSCCs harbour fewer cells expressing the CSC enrichment markers CD44 and CD98. Furthermore, OS and PFS were significantly worse for patients with HPV-positive OPSCC with a high percentage of CD98-positive cells.
已经提出了几种假说来解释 HPV 阳性口咽鳞状细胞癌（OPSCC）患者预后较好的原因，其中之一是对（放）化疗的敏感性较高。先前的研究表明，OPSCC 患者的治疗失败是由癌症干细胞（CSC）的耐药性引起的。本研究旨在评估 HPV 阳性 OPSCC 患者中 CSC 数量与预后的关系。
纳入了 2000 年至 2006 年在荷兰两所大学医院接受治疗的所有 OPSCC 患者（n=711）。通过 p16 免疫组化染色，然后进行 HPV DNA GP5+/6+聚合酶链反应（PCR）检测肿瘤组织标本中 HPV 的存在。通过免疫组织化学检测肿瘤 CSC 标志物 CD44 和 CD98 的存在和强度，并进行半定量评分。比较 HPV 状态与低和高 CD44/CD98 表达患者的总生存率（OS）和无进展生存率（PFS）。
HPV 阳性肿瘤的 CD44 和 CD98 表达细胞比例低于 HPV 阴性肿瘤（p<0.001，卡方检验）。在 HPV 阳性 OPSCC 患者中，CD98 阳性肿瘤细胞比例高与 5 年 OS 和 PFS 显著降低相关（OS：36.4%和 PFS：27.3%，与 CD98 阳性细胞比例低的患者相比（OS：71.9%和 PFS：70.5%）（p<0.001）。
HPV 阳性 OPSCC 中表达 CSC 富集标志物 CD44 和 CD98 的细胞较少。此外，HPV 阳性 OPSCC 患者中 CD98 阳性细胞比例高的患者 OS 和 PFS 明显更差。
