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人乳头瘤病毒流行率、基因型分布以及阴道癌的预后因素。

Human papillomavirus prevalence, genotype distribution, and prognostic factors of vaginal cancer.

机构信息

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University College of Medicine, Taoyuan, Taiwan.

Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University College of Medicine, Taoyuan, Taiwan.

出版信息

Int J Cancer. 2024 Dec 1;155(11):1996-2008. doi: 10.1002/ijc.35105. Epub 2024 Jul 24.

DOI:10.1002/ijc.35105
PMID:39046705
Abstract

We aimed to investigate human papillomavirus (HPV) prevalence and genotype distribution and prognostic factors in vaginal cancer (VC). VC patients who received treatment between 1989 and 2020 were retrospectively reviewed. L1 general polymerase chain reaction (PCR) followed by HPV Blot (King Car, I-Lan, Taiwan) and E6 type-specific-PCR were performed for genotyping firstly. P16 and p53 immunohistochemistry staining was performed. Univariate and multivariate analyses identified predictors of clinical outcomes.79 VC patients were eligible for analysis. 73 patients (92.4%) were squamous cell carcinoma (SCC) and 6 (7.6%) as non-SCC. The median follow-up time was 134.3 months (range 0.9-273.4). Among nine initially HPV-negative cases, seven were identified as being positive through HPV16/18/45/52/58 whole-genome amplification followed by Sanger sequencing (WGASS). HPV DNA sequences were detected in 98.6% of SCC and 83.3% of non-SCC, respectively, with HPV16 (49.4%), HPV52 (15.2%) and HPV58 (8.9%) being predominant. Patients with paraaortic lymph node (LN) metastasis had a 5-year cancer-specific survival (CSS) rate of 0%. Multivariate analysis revealed that only p16 and stage were significantly correlated with prognosis. Variables with strong correlations (p16- and HPV-positivity, LN metastasis and stage), were included in models 2-5 alternatively. Stage III/IV (hazard ratio [HR] = 3.64-4.56) and LN metastasis (HR = 2.81-3.44) were significant negative predictors of CSS, whereas p16-positivity (HR = 0.29-0.32) and HPV-positivity (HR = 0.14) were related to better prognosis. In conclusion, 97.5% of VCs were HPV-positive with WGASS. Stage III/IV and LN metastasis were significant negative predictors, whereas p16- and HPV-positivity were significantly associated with better prognosis.

摘要

我们旨在研究阴道癌(VC)中的人乳头瘤病毒(HPV)流行率和基因型分布以及预后因素。回顾性分析了 1989 年至 2020 年间接受治疗的 VC 患者。首先进行 L1 通用聚合酶链反应(PCR),然后进行 HPV Blot(King Car,I-Lan,台湾)和 E6 型特异性-PCR 进行基因分型。进行 P16 和 p53 免疫组织化学染色。进行单变量和多变量分析以确定临床结果的预测因素。79 例 VC 患者符合分析条件。73 例(92.4%)为鳞状细胞癌(SCC),6 例(7.6%)为非 SCC。中位随访时间为 134.3 个月(范围 0.9-273.4)。最初 9 例 HPV 阴性的患者中,有 7 例通过 HPV16/18/45/52/58 全基因组扩增后 Sanger 测序(WGASS)确定为阳性。SCC 和非 SCC 中分别检测到 98.6%和 83.3%的 HPV DNA 序列,主要为 HPV16(49.4%)、HPV52(15.2%)和 HPV58(8.9%)。有腹主动脉旁淋巴结(LN)转移的患者 5 年癌症特异性生存率(CSS)为 0%。多变量分析显示,只有 p16 和分期与预后显著相关。将具有强相关性的变量(p16 和 HPV 阳性、LN 转移和分期)依次包含在模型 2-5 中。III/IV 期(风险比[HR] = 3.64-4.56)和 LN 转移(HR = 2.81-3.44)是 CSS 的显著负预测因子,而 p16 阳性(HR = 0.29-0.32)和 HPV 阳性(HR = 0.14)与更好的预后相关。总之,97.5%的 VC 为 HPV 阳性,采用 WGASS。III/IV 期和 LN 转移是显著的负预测因子,而 p16 和 HPV 阳性与更好的预后显著相关。

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