Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clinic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Faculty of Medicine-University of Barcelona, Barcelona, Spain.
Gynecol Oncol. 2011 Sep;122(3):509-14. doi: 10.1016/j.ygyno.2011.05.016. Epub 2011 Jun 8.
Two independent pathways in the development of vulvar squamous cell carcinoma (VSCC) have been described, one related to and the other independent of high-risk human papillomavirus (HR-HPV). The aim of our study was to evaluate whether the HPV status has a prognostic significance or can predict response to radiotherapy.
All VSCC diagnosed from 1995 to 2009 were retrospectively evaluated (n=98). HPV infection was detected by amplification of HPV DNA by PCR using SPF-10 primers and typed by the INNO-LIPA HPV research assay. p16(INK4a) expression was determined by immunohistochemistry. Disease-free and overall survival (DFS and OS) were estimated by Kaplan-Meier analysis with the log-rank test and a multivariate Cox proportional hazard's model.
HR-HPV DNA was detected in 19.4% of patients. HPV16 was the most prevalent genotype (73.7% of cases). p16(INK4a) stained 100% HPV-positive and 1.3% HPV-negative tumors (p<.001). No differences were found between HPV-positive and -negative tumors in terms of either DFS (39.8% vs. 49.8% at 5 years; p=.831), or OS (67.2% vs. 71.4% at 5 years; p=.791). No differences in survival were observed between HPV-positive and -negative patients requiring radiotherapy (hazard ratio [HR] 1.04, 95% confidence interval [CI] .45 to 2.41). FIGO stages III-IV (p=.002), lymph node metastasis (p=.030), size ≥ 20 mm (p=.023), invasion depth (p=.020) and ulceration (p=.032) were associated with increased mortality but in multivariated only lymph node metastasis retained the association (HR 13.28, 95% CI 1.19 to 148.61).
HPV-positive and -negative VSCCs have a similar prognosis. Radiotherapy does not increase survival in HPV-positive women.
外阴鳞状细胞癌（VSCC）的发展有两种独立的途径，一种与高危型人乳头瘤病毒（HR-HPV）有关，另一种则独立于 HR-HPV。我们的研究旨在评估 HPV 状态是否具有预后意义，或能否预测对放疗的反应。
回顾性评估了 1995 年至 2009 年期间诊断的所有 VSCC（n=98）。使用 SPF-10 引物通过聚合酶链反应扩增 HPV DNA 来检测 HPV 感染，并通过 INNO-LIPA HPV 研究检测试剂盒进行 HPV 定型。通过免疫组化法测定 p16(INK4a)的表达。采用 Kaplan-Meier 分析和对数秩检验及多变量 Cox 比例风险模型评估无病生存（DFS）和总生存（OS）。
19.4%的患者检测到 HR-HPV DNA。HPV16 是最常见的基因型（73.7%的病例）。p16(INK4a)染色阳性 100%的 HPV 阳性肿瘤和 1.3%的 HPV 阴性肿瘤（p<.001）。HPV 阳性和阴性肿瘤在 DFS（5 年时分别为 39.8%和 49.8%；p=.831）或 OS（5 年时分别为 67.2%和 71.4%；p=.791）方面均无差异。需要放疗的 HPV 阳性和阴性患者的生存无差异（风险比 [HR] 1.04，95%置信区间 [CI].45 至 2.41）。FIGO 分期 III-IV（p=.002）、淋巴结转移（p=.030）、大小≥20mm（p=.023）、浸润深度（p=.020）和溃疡（p=.032）与死亡率增加相关，但在多变量分析中只有淋巴结转移与死亡率相关（HR 13.28，95%CI 1.19 至 148.61）。
HPV 阳性和阴性 VSCC 具有相似的预后。放疗不能提高 HPV 阳性女性的生存率。
