Jo Solomon, Juhasz Agnes, Zhang Keqiang, Ruel Christopher, Loera Sofia, Wilczynski Sharon P, Yen Yun, Liu Xiyong, Ellenhorn Joshua, Lim Dean, Paz Benjamin, Somlo George, Vora Nayana, Shibata Stephen
City of Hope National Medical Center, 1500 East Duarte Rd, Duarte, CA 91010, U.S.A.
Anticancer Res. 2009 May;29(5):1467-74.
The aim of this study was to determine the presence of high-risk HPV-16 in patients with HNSCC, assess the impact of HPV status on treatment response and survival in this select cohort treated with combined modality therapy and to identify the differences in HIF-1alpha and VEGF expression in HPV-positive and -negative tumors.
Patients had resectable, untreated stage III, IV HNSCC of the oral cavity, oropharynx, hyopharynx or larynx, and stage II cancer of the base of tongue, hypopharynx and larynx. HPV status was determined by conventional PCR in fresh frozen biopsy samples and by Taqman PCR assay on formalin-fixed, paraffin-embedded specimens. HIF-1alpha and VEGF expression were assessed by quantitative real-time PCR (RT-PCR). Multivariate Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) based on HPV status.
HPV-16 was detected in 14 of 24 evaluable cases. There were no significant differences in response rates after neoadjuvant chemotherapy (86% vs. 90%) in HPV-positive and HPV-negative patients, respectively. There was a trend toward better progression-free (HR=0.15, 95% CI=0.002-12.54; p=0.06) and overall survival (HR=0.14, 95% CI=0.001-14.12; p=0.10) for HPV-positive patients. In a subset of 13 fresh frozen samples, RT-PCR revealed a significant increase in VEGF mRNA levels in HPV-positive tumors (p<0.01). No difference was seen for HIF-1alpha expression.
HPV presence portended a better prognosis in patients with oropharyngeal SCC treated with a multimodality treatment in a prospective clinical trial. The level of VEGF mRNA was up-regulated in HPV-16-positive tumors possibly through an HIF-1 independent manner.
本研究的目的是确定头颈部鳞状细胞癌（HNSCC）患者中高危型人乳头瘤病毒16型（HPV-16）的存在情况，评估HPV状态对接受综合治疗的这一特定队列患者治疗反应和生存的影响，并确定HPV阳性和阴性肿瘤中缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子（VEGF）表达的差异。
患者患有可切除的、未经治疗的口腔、口咽、下咽或喉的III期、IV期HNSCC，以及舌根、下咽和喉的II期癌症。HPV状态通过新鲜冷冻活检样本中的常规聚合酶链反应（PCR）以及福尔马林固定、石蜡包埋标本上的Taqman PCR检测来确定。HIF-1α和VEGF表达通过定量实时聚合酶链反应（RT-PCR）进行评估。多变量Cox比例风险回归分析用于根据HPV状态计算风险比（HRs）和95%置信区间（CIs）。
在24例可评估病例中的14例检测到HPV-16。HPV阳性和阴性患者新辅助化疗后的缓解率分别为86%和90%，无显著差异。HPV阳性患者的无进展生存期（HR=0.15，95%CI=0.002-12.54；p=0.06）和总生存期（HR=0.14，95%CI=0.001-14.12；p=0.10）有改善趋势。在13个新鲜冷冻样本的子集中，RT-PCR显示HPV阳性肿瘤中VEGF mRNA水平显著升高（p<0.01）。HIF-1α表达未见差异。
在前瞻性临床试验中，对于接受多模式治疗的口咽鳞状细胞癌患者，HPV的存在预示着更好的预后。HPV-16阳性肿瘤中VEGF mRNA水平可能通过不依赖HIF-1的方式上调。
