Tan Louise Soo Yee, Fredrik Petersson, Ker Liang, Yu Feng Gang, Wang De Yun, Goh Boon Cher, Loh Kwok Seng, Lim Chwee Ming
Department of Otolaryngology-Head and Neck Surgery, National University Health System Singapore, Singapore 119228.
Department of Pathology, National University Health System Singapore, Singapore 119228.
Oncotarget. 2016 Dec 27;7(52):86730-86739. doi: 10.18632/oncotarget.13502.
Human papillomavirus (HPV), especially HPV16 genotype, is associated with oropharyngeal squamous cell carcinoma (OPSCC). We aim to determine the prevalence and characterize the high-risk (HR)-HPV genotypes in head and neck SCC (HNSCC) in a South-East Asian multi-ethnic society in Singapore and examine its prognostic significance.159 HNSCC archival tissue samples were retrieved and tumour DNA was screened for 18 HR-HPV genotypes using a PCR-based assay (Qiagen, digene HPV genotyping RH test). P16 protein overexpression was identified using immunohistochemistry (IHC). Statistical correlation between clinical outcomes were performed between HPV-positive and negative HNSCC patients.Six HR-HPVs (HPV16, 18, 31, 45, 56, 68) were detected in 90.6% of HNSCC; and 79.9% had multiple HPV genotypes detected. HPV31 and HPV45 were the most prevalent (79.2% and 87.4%, respectively); and HPV16 was predominantly found in OPSCC (p < 0.001). HPV-DNA PCR assay yielded a high sensitivity (96%) but low specificity (11%) when compared to p16 immunohistochemistry as the reference standard.P16-positive HNSCC was predominantly observed in OPSCC (73.7%; p = 0.005); and p16-positive OPSCC exhibited improved overall survival compared to p16-negative OPSCC (p = 0.022). Similarly, smoking and alcohol consumption were poor prognostic factors of overall survival (p = 0.007; p = 0.01) in OPSCC patients.HR-HPVs were identified in 90.6% of HNSCC patients using the HPV-DNA PCR assay. This test had a poor specificity when compared to p16 IHC; making it an unreliable detection technique in selecting patients for radiation dose de-escalation treatment protocol. P16-positive tumor was predominantly found in the oropharynx these patients demonstrated better overall survival than those with p16-negative OPSCC.
人乳头瘤病毒（HPV），尤其是HPV16基因型，与口咽鳞状细胞癌（OPSCC）相关。我们旨在确定新加坡一个东南亚多民族社会中头颈部鳞状细胞癌（HNSCC）的高危（HR）-HPV基因型的流行情况并对其进行特征分析，并研究其预后意义。检索了159份HNSCC存档组织样本，并使用基于PCR的检测方法（Qiagen，digene HPV基因分型RH检测）对头颈部鳞状细胞癌的18种HR-HPV基因型进行肿瘤DNA筛查。使用免疫组织化学（IHC）鉴定p16蛋白过表达。对HPV阳性和阴性的HNSCC患者的临床结局进行统计相关性分析。在90.6%的HNSCC中检测到6种HR-HPV（HPV16、18、31、45、56、68）；79.9%检测到多种HPV基因型。HPV31和HPV45最为常见（分别为79.2%和87.4%）；HPV16主要见于OPSCC（p<0.001）。以p16免疫组织化学作为参考标准时，与p16免疫组织化学相比，HPV-DNA PCR检测的敏感性较高（96%），但特异性较低（11%）。p16阳性的HNSCC主要见于OPSCC（73.7%；p=0.005）；与p16阴性的OPSCC相比，p16阳性的OPSCC总生存期有所改善（p=0.022）。同样，吸烟和饮酒是OPSCC患者总生存期的不良预后因素（p=0.007；p=0.01）。使用HPV-DNA PCR检测在90.6%的HNSCC患者中鉴定出HR-HPV。与p16免疫组化相比，该检测的特异性较差；这使其在选择患者进行放射剂量递减治疗方案时成为一种不可靠的检测技术。p16阳性肿瘤主要见于口咽，这些患者的总生存期优于p16阴性的OPSCC患者。
