Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Int J Cancer. 2013 Apr 1;132(7):1565-71. doi: 10.1002/ijc.27821. Epub 2012 Nov 23.
Human papillomavirus (HPV) infection has been etiologically linked to oropharyngeal squamous cell carcinoma (OPSCC). The prevalence of HPV-positive OPSCC varies between studies, ranging from 20 to 90%. This may be related to the lack of a standardized HPV detection assay as well as to the time period in which HPV prevalence is investigated, as rising incidence rates are reported over the last decades. Here, we validated our previously defined test algorithm for HPV detection in formalin-fixed paraffin-embedded (FFPE) tumor specimen consisting of p16(INK4A) immunostaining followed by high-risk HPV DNA detection by GP5+/6+ PCR on the positive cases (Smeets et al., Int J Cancer 2007;121:2465-72). In addition, we analyzed HPV prevalence rates in OPSCCs in the years 1990-2010. The test algorithm was validated on a consecutive series of 86 OPSCCs collected during 2008-2011, of which both fresh frozen and FFPE samples were available. We performed HPV-E6 RT-PCR on the frozen samples as gold standard and applied the algorithm to the corresponding FFPE samples. The test algorithm showed an accuracy of 98%. Using the validated algorithm, we determined the presence of an oncogenic HPV infection in 240 OPSCCs of patients diagnosed in the years 1990-2010 at our center. A significant increase in the proportion of HPV-positive samples was observed, from 5.1% in 1990 to 29.0% in 2010 (p = 0.001). In conclusion, we confirmed the accuracy of the test algorithm for HPV detection in FFPE tumor specimen and we found a significant increase in the prevalence of HPV in OPSCC over the last two decades at our center.
人乳头瘤病毒（HPV）感染与口咽鳞状细胞癌（OPSCC）有病因学联系。HPV 阳性 OPSCC 的患病率因研究而异，范围为 20%至 90%。这可能与缺乏标准化的 HPV 检测方法以及 HPV 流行率调查的时间有关，因为过去几十年报告的发病率呈上升趋势。在这里，我们验证了我们之前定义的用于检测福尔马林固定石蜡包埋（FFPE）肿瘤标本中 HPV 的测试算法，该算法包括 p16（INK4A）免疫染色，然后对阳性病例进行高危 HPV DNA 检测 GP5+/6+PCR（Smeets 等人，Int J Cancer 2007；121:2465-72）。此外，我们分析了 1990 年至 2010 年 OPSCC 中的 HPV 患病率。该测试算法在 2008 年至 2011 年期间收集的连续 86 例 OPSCC 系列中进行了验证，其中既有新鲜冷冻样本也有 FFPE 样本。我们对冷冻样本进行了 HPV-E6 RT-PCR 作为金标准，并将算法应用于相应的 FFPE 样本。该测试算法的准确率为 98%。使用验证后的算法，我们确定了我们中心在 1990 年至 2010 年期间诊断的 240 例 OPSCC 患者存在致癌 HPV 感染。HPV 阳性样本的比例显著增加，从 1990 年的 5.1%增加到 2010 年的 29.0%（p = 0.001）。总之，我们证实了该测试算法用于检测 FFPE 肿瘤标本中 HPV 的准确性，并发现我们中心过去二十年 OPSCC 中 HPV 流行率显著增加。
