对临床病理因素的详细分析表明，手术治疗的HPV阳性和阴性口咽癌在结局和预后因素方面存在明显差异。
Detailed Analysis of Clinicopathologic Factors Demonstrate Distinct Difference in Outcome and Prognostic Factors Between Surgically Treated HPV-Positive and Negative Oropharyngeal Cancer.
作者信息
Iyer N Gopalakrishna, Dogan Snjezana, Palmer Frank, Rahmati Rahmatullah, Nixon Iain J, Lee Nancy, Patel Snehal G, Shah Jatin P, Ganly Ian
机构信息
Department of Head and Neck Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Singhealth/Duke-NUS Head and Neck Centre, National Cancer Centre, Singapore, Singapore.
出版信息
Ann Surg Oncol. 2015 Dec;22(13):4411-21. doi: 10.1245/s10434-015-4525-0. Epub 2015 Mar 24.
BACKGROUND
Oropharyngeal cancers (OPC) secondary to human papillomavirus (HPV) infections likely represent a completely different disease compared with conventional head and neck cancers. Our objective was to analyze a surgically treated cohort to determine predictors of outcome in HPV-positive versus HPV-negative patients.
METHODS
HPV positivity was inferred based on p16-immunohistochemistry. Data was available for 201 patients with OPC treated with surgical resection with/without adjuvant radiotherapy between 1985 and 2005. Subsite distribution was: 66 (33 %) tonsil, 46 (23 %) soft palate, and 89 (44 %) tongue base. Patients were classified into low-, intermediate-, and high-risk groups based on p16 status and smoking history. Outcomes stratified by p16 status and risk groups were determined by the Kaplan-Meier method. Factors predictive of outcome were determined by univariate and multivariate analyses.
RESULTS
In this cohort, 30 % had locally advanced disease (pT3/T4) and 71 % had nodal metastasis. The 5-year overall (OS), disease-specific, and recurrence-free survival rates were 60, 76, and 66 %, respectively. There were 22 % low-, 34 % intermediate-, and 44 % high-risk patients. Patients who were p16-positive had better survival compared with p16-negative (OS, 74 vs. 44 %; p < .001). Similarly, low-risk group patients had a better survival compared with intermediate- and high-risk groups (OS, 76, 68, 45 %, respectively, p < .001). Independent predictors of survival in p16-negative patients included margin status, lymphovascular invasion, pN status, and extracapsular spread. In contrast, none of these were predictive in p16-positive patients.
CONCLUSIONS
Surgically treated patients with p16-positive OPC have superior survival compared with p16-negative patients. Outcomes in p16-positive and p16-negative OPC are determined by different prognostic factors supporting the notion that these are very different diseases. These should be incorporated into future clinical trials design.
背景
与传统头颈癌相比，人乳头瘤病毒（HPV）感染继发的口咽癌（OPC）可能代表一种完全不同的疾病。我们的目的是分析一组接受手术治疗的患者，以确定HPV阳性与HPV阴性患者的预后预测因素。
方法
基于p16免疫组化推断HPV阳性。有1985年至2005年间201例接受手术切除并伴有或不伴有辅助放疗的OPC患者的数据。亚部位分布为：扁桃体66例（33%）、软腭46例（23%）、舌根89例（44%）。根据p16状态和吸烟史将患者分为低、中、高风险组。通过Kaplan-Meier方法确定按p16状态和风险组分层的预后。通过单因素和多因素分析确定预后的预测因素。
结果
在该队列中，30%患有局部晚期疾病（pT3/T4），71%有淋巴结转移。5年总生存率（OS）、疾病特异性生存率和无复发生存率分别为60%、76%和66%。低风险患者占22%，中风险患者占34%，高风险患者占44%。p16阳性患者的生存率高于p16阴性患者（OS分别为74%和44%；p < 0.001）。同样，低风险组患者的生存率高于中、高风险组（OS分别为76%、68%、45%，p < 0.001）。p16阴性患者生存的独立预测因素包括切缘状态、脉管浸润、pN状态和包膜外扩散。相比之下，这些因素在p16阳性患者中均无预测作用。
结论
与p16阴性患者相比，接受手术治疗的p16阳性OPC患者生存率更高。p16阳性和p16阴性OPC的预后由不同的预后因素决定，支持了这是两种非常不同疾病的观点。这些应纳入未来的临床试验设计中。
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