Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen, Denmark.
Unit of Statistics and Pharmacoepidemiology, Danish Cancer Society Research Center, Strandboulevarden 49, Copenhagen, Denmark.
Gynecol Oncol. 2019 Jan;152(1):208-217. doi: 10.1016/j.ygyno.2018.10.015. Epub 2018 Nov 8.
The tumor suppressor proteins p16 and p53 have been suggested to have prognostic value in some human papillomavirus (HPV)-associated cancers, however, this has been less well established for vulvar cancer. The aim of this review and meta-analysis was to examine the prognostic value of p16 and p53 expression status on survival after vulvar squamous cell carcinoma (VSCC). We conducted a thorough systematic literature search of multiple databases to identify studies examining survival after histolocally verified VSCC that were tested for p16 and/or p53. A total of 18 eligible studies were included. Using a fixed-effects model we calculated study-specific and pooled hazard ratios (HRs) of 5-year overall survival (OS). In the analyses of OS, we included 475 VSCC cases tested for p16 expression of which 38% were p16 positive. The pooled HR was 0.40 (95% CI: 0.29-0.55). In addition, the majority of results from studies with adjusted analyses on the prognostic value of p16 indicated that p16 expression status could be an independent prognostic marker for OS in women diagnosed with VSCC, and the same pattern was seen for disease specific survival (DSS). We also included 310 VSCC cases tested for p53 expression of which 54% were p53 positive. The pooled HR was 1.81 (95% CI: 1.22-2.68) indicating that p53 positive VSCC have a significantly lower 5-year OS compared to p53 negative. The results in relation to p53 reported from adjusted analyses OS and on DSS and disease free survival were more equivocal. This meta-analysis and review suggests that p53 and especially p16 expression status are of prognostic importance in women diagnosed with VSCC. This may be clinically important in the future design of targeted therapy and when planning the optimal follow-up strategy. Future studies should include the combined use of biomarkers such as p16, p53 and HPV status.
抑癌蛋白 p16 和 p53 已被证实对某些人乳头瘤病毒（HPV）相关癌症具有预后价值，然而，在外阴癌中其价值尚未得到充分证实。本综述和荟萃分析的目的是探讨 p16 和 p53 表达状态在外阴鳞状细胞癌（VSCC）患者生存中的预后价值。我们对多个数据库进行了全面的系统文献检索，以确定检查 p16 和/或 p53 表达状态与外阴鳞癌生存情况的研究。共有 18 项符合条件的研究被纳入。使用固定效应模型，我们计算了组织学证实的 VSCC 患者的 5 年总生存率（OS）的研究特异性和汇总风险比（HR）。在 OS 分析中，我们纳入了 475 例 p16 表达检测的 VSCC 病例，其中 38%为 p16 阳性。汇总 HR 为 0.40（95%CI：0.29-0.55）。此外，大多数经过调整分析 p16 预后价值的研究结果表明，p16 表达状态可能是 VSCC 患者 OS 的独立预后标志物，疾病特异性生存率（DSS）也存在同样的模式。我们还纳入了 310 例 p53 表达检测的 VSCC 病例，其中 54%为 p53 阳性。汇总 HR 为 1.81（95%CI：1.22-2.68），表明 p53 阳性 VSCC 的 5 年 OS 显著低于 p53 阴性。与调整分析 OS、DSS 和无病生存率有关的 p53 报告结果更不确定。本荟萃分析和综述表明，p53 尤其是 p16 表达状态在外阴癌患者中具有重要的预后意义。这在未来靶向治疗的设计和最佳随访策略的规划中可能具有重要的临床意义。未来的研究应包括联合使用 p16、p53 和 HPV 状态等生物标志物。
