Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan.
Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan.
Int J Radiat Oncol Biol Phys. 2014 Mar 1;88(3):580-8. doi: 10.1016/j.ijrobp.2013.11.246.
To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in nonendemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status.
Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBV and high-risk HPV. EBV status was determined by the use of in situ hybridization for EBV encoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex polymerase chain reaction MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viral status.
Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPV-positive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBV and HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P<.001). The racial distribution of the study population was 74% white, 15% African American, and 11% Asian/Middle Eastern. Among HPV-positive patients, 94% were white. At a median follow-up time of 7 years, HPV-positive and EBV/HPV-negative tumors exhibited worse outcomes than did EBV-positive tumors, including decreased overall survival (hazard ratio [HR] 2.98, P=.01; and HR 3.89, P=.002), progression-free survival (HR 2.55, P=.02; and HR 4.04, P<.001), and locoregional control (HR 4.01, P=.03; and HR 6.87, P=.001).
In our Midwestern population, high-risk HPV infection may play an etiologic role in the development of nonendemic, EBV-negative NPC. Compared with EBV-positive NPC, HPV-positive and EBV/HPV-negative NPC are associated with worse outcomes. A larger confirmatory study is needed to validate these findings.
研究人乳头瘤病毒（HPV）与非流行地区鼻咽癌（NPC）中 Epstein-Barr 病毒（EBV）之间的关系，并评估病毒状态的预后意义。
对 1985 年至 2011 年间诊断的 62 例原发性 NPC 患者的石蜡包埋肿瘤标本进行 EBV 和高危型 HPV 分析。通过 EBV 编码 RNA 的原位杂交确定 EBV 状态。HPV 状态通过 p16 免疫组化和多重聚合酶链反应 MassArray 来评估 HPV 类型。使用比例风险模型比较按病毒状态分层的患者的死亡风险。
在 61 例可评估肿瘤中，26 例（43%）为 EBV 阳性/HPV 阴性，18 例（30%）为 HPV 阳性/EBV 阴性，17 例（28%）为 EBV/HPV 阴性。EBV 和 HPV 感染是相互排斥的。HPV 阳性与世界卫生组织（WHO）2 级肿瘤、年龄较大和吸烟显著相关（均 P<.001）。研究人群的种族分布为 74%白人、15%非裔美国人、11%亚洲/中东人。在 HPV 阳性患者中，94%为白人。中位随访时间为 7 年，HPV 阳性和 EBV/HPV 阴性肿瘤的结局比 EBV 阳性肿瘤差，包括总生存（风险比 [HR] 2.98，P=.01；和 HR 3.89，P=.002）、无进展生存（HR 2.55，P=.02；和 HR 4.04，P<.001）和局部区域控制（HR 4.01，P=.03；和 HR 6.87，P=.001）。
在我们的中西部人群中，高危型 HPV 感染可能在非流行地区 EBV 阴性 NPC 的发生中起病因作用。与 EBV 阳性 NPC 相比，HPV 阳性和 EBV/HPV 阴性 NPC 与较差的结局相关。需要更大的验证性研究来验证这些发现。
