Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO), IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Department of Medical Oncology, Catalan Institute of Oncology (ICO), ONCOBELL, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; University of Barcelona, Barcelona, Spain.
Oral Oncol. 2018 Mar;78:137-144. doi: 10.1016/j.oraloncology.2018.01.010. Epub 2018 Feb 20.
The etiologic role of human papillomaviruses (HPV) in oropharyngeal cancer (OPC) is well established. Nevertheless, information on survival differences by anatomic sub-site or treatment remains scarce, and it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value.
We conducted a retrospective cohort study of all patients diagnosed with a primary OPC in four Catalonian hospitals from 1990 to 2013. Formalin-fixed, paraffin-embedded cancer tissues were subjected to histopathological evaluation, DNA quality control, HPV-DNA detection, and p16/pRb/p53/Cyclin-D1 immunohistochemistry. HPV-DNA positive and a random sample of HPV-DNA negative cases were subjected to HPV-E6*I mRNA detection. Demographic, tobacco/alcohol use, clinical and follow-up data were collected. Multivariate models were used to evaluate factors associated with HPV positivity as defined by four different HPV-relatedness definitions. Proportional-hazards models were used to compare the risk of death and recurrence among HPV-related and non-related OPC.
788 patients yielded a valid HPV-DNA result. The percentage of positive cases was 10.9%, 10.2%, 8.5% and 7.4% for p16, HPV-DNA, HPV-DNA/HPV-E6*I mRNA, and HPV-DNA/p16, respectively. Being non-smoker or non-drinker was consistently associated across HPV-relatedness definitions with HPV positivity. A suggestion of survival differences between anatomic sub-sites and treatments was observed. Double positivity for HPV-DNA/p16 showed strongest diagnostic accuracy and prognostic value.
Double positivity for HPV-DNA/p16, a test that can be easily implemented in the clinical practice, has optimal diagnostic accuracy and prognostic value. Our results have strong clinical implications for patients' classification and handling and also suggest that not all the HPV-related OPC behave similarly.
人乳头瘤病毒（HPV）在口咽癌（OPC）中的病因作用已得到充分证实。然而，关于解剖亚部位或治疗方法的生存差异的信息仍然很少，并且HPV 相关性的最佳诊断准确性和预后价值定义仍不清楚。
我们对 1990 年至 2013 年在加泰罗尼亚的四家医院诊断为原发性 OPC 的所有患者进行了回顾性队列研究。福尔马林固定、石蜡包埋的癌组织进行了组织病理学评估、DNA 质量控制、HPV-DNA 检测以及 p16/pRb/p53/Cyclin-D1 免疫组化。HPV-DNA 阳性和 HPV-DNA 阴性的随机样本进行 HPV-E6*I mRNA 检测。收集人口统计学、烟草/酒精使用、临床和随访数据。使用多变量模型评估与四种不同 HPV 相关性定义相关的 HPV 阳性的相关因素。使用比例风险模型比较 HPV 相关和非相关 OPC 之间的死亡和复发风险。
788 例患者的 HPV-DNA 结果有效。p16、HPV-DNA、HPV-DNA/HPV-E6*I mRNA 和 HPV-DNA/p16 的阳性率分别为 10.9%、10.2%、8.5%和 7.4%。非吸烟或非饮酒在 HPV 相关性定义中始终与 HPV 阳性相关。观察到解剖亚部位和治疗方法之间存在生存差异的迹象。HPV-DNA/p16 的双重阳性显示出最强的诊断准确性和预后价值。
HPV-DNA/p16 的双重阳性，一种可以在临床实践中轻松实施的测试，具有最佳的诊断准确性和预后价值。我们的结果对口咽癌患者的分类和处理具有重要的临床意义，也表明并非所有 HPV 相关的 OPC 都具有相似的行为。
