摘要

BACKGROUND:High-risk human papillomavirus (hrHPV) infection is established as the major cause of invasive cervical cancer (ICC). However, whether hrHPV status in the tumor is associated with subsequent prognosis of ICC is controversial. We aim to evaluate the association between tumor hrHPV status and ICC prognosis using national registers and comprehensive human papillomavirus (HPV) genotyping. METHODS AND FINDINGS:In this nationwide population-based cohort study, we identified all ICC diagnosed in Sweden during the years 2002-2011 (4,254 confirmed cases), requested all archival formalin-fixed paraffin-embedded blocks, and performed HPV genotyping. Twenty out of 25 pathology biobanks agreed to the study, yielding a total of 2,845 confirmed cases with valid HPV results. Cases were prospectively followed up from date of cancer diagnosis to 31 December 2015, migration from Sweden, or death, whichever occurred first. The main exposure was tumor hrHPV status classified as hrHPV-positive and hrHPV-negative. The primary outcome was all-cause mortality by 31 December 2015. Five-year relative survival ratios (RSRs) were calculated, and excess hazard ratios (EHRs) with 95% confidence intervals (CIs) were estimated using Poisson regression, adjusting for education, time since cancer diagnosis, and clinical factors including age at cancer diagnosis and International Federation of Gynecology and Obstetrics (FIGO) stage. Of the 2,845 included cases, hrHPV was detected in 2,293 (80.6%), and we observed 1,131 (39.8%) deaths during an average of 6.2 years follow-up. The majority of ICC cases were diagnosed at age 30-59 years (57.5%) and classified as stage IB (40.7%). hrHPV positivity was significantly associated with screen-detected tumors, young age, high education level, and early stage at diagnosis (p < 0.001). The 5-year RSR compared to the general female population was 0.74 (95% CI 0.72-0.76) for hrHPV-positive cases and 0.54 (95% CI 0.50-0.59) for hrHPV-negative cases, yielding a crude EHR of 0.45 (95% CI 0.38-0.52) and an adjusted EHR of 0.61 (95% CI 0.52-0.71). Risk of all-cause mortality as measured by EHR was consistently and statistically significantly lower for cases with hrHPV-positive tumors for each age group above 29 years and each FIGO stage above IA. The difference in prognosis by hrHPV status was highly robust, regardless of the clinical, histological, and educational characteristics of the cases. The main limitation was that, except for education, we were not able to adjust for lifestyle factors or other unmeasured confounders. CONCLUSIONS:In this study, women with hrHPV-positive cervical tumors had a substantially better prognosis than women with hrHPV-negative tumors. hrHPV appears to be a biomarker for better prognosis in cervical cancer independent of age, FIGO stage, and histological type, extending information from already established prognostic factors. The underlying biological mechanisms relating lack of detectable tumor hrHPV to considerably worse prognosis are not known and should be further investigated.

译文

背景: 高危型人乳头瘤病毒 (hrHPV) 感染是浸润性宫颈癌 (ICC) 的主要原因。然而,肿瘤中的 hrHPV 状态是否与 ICC 的后续预后相关是有争议的。我们的目的是使用国家注册和全面的人乳头瘤病毒 (HPV) 基因分型来评估肿瘤 hrHPV 状态和 ICC 预后之间的关联。方法和结果: 在这项全国范围的基于人群的队列研究中,我们确定了 2002年至 2011 在瑞典诊断的所有 ICC (4,254 例确诊病例), 要求所有档案福尔马林固定石蜡包埋块,并进行 HPV 基因分型。25 个病理生物库中有 20 个同意这项研究,总共产生了 2,845 例有效的人乳头状瘤病毒确诊病例。从癌症诊断日期到 2015年12月31日,从瑞典移民或死亡,以先发生者为准,对病例进行前瞻性随访。主要暴露是肿瘤 hrhvv 状态,分为 hrhvv 阳性和 hrhvv 阴性。主要结果是到 2015年12月31日的全因死亡率。计算五年相对存活率 (RSRs),并使用泊松回归估计 95% 置信区间 (CIs) 的超额风险比 (EHRs),调整教育, 自癌症诊断以来的时间,以及包括癌症诊断年龄和国际妇产科联合会 (FIGO) 阶段在内的临床因素。在纳入的 2,845 例病例中,hrHPV 在 2,293 例 (80.6%) 中被检测到,我们在平均 1,131 年的随访中观察到 39.8% 例 (6.2) 死亡。大多数 ICC 病例在 30-59 岁 (57.5%) 被诊断为 IB 期 (40.7%)。HrHPV 阳性与筛查发现的肿瘤、年轻、受教育程度高和诊断早期显著相关 (p & lt; 0.001)。与普通女性人群相比,hrpv 阳性病例的 5 年 RSR 为 0.74 (95% CI 0.72-0.76),hrpv 阴性病例为 0.54 (95% CI 0.50-0.59), 产生 0.45 的原始 EHR (95% CI 0.38-0.52) 和 0.61 的调整 EHR (95% CI 0.52-0.71)。由 EHR 测量的全因死亡率的风险,对于 29 岁以上和 IA 以上的每一个 FIGO 阶段的 hrhvv 阳性肿瘤病例来说,在统计学上持续显著较低。无论病例的临床、组织学和教育特征如何,hrHPV 状态在预后上的差异是高度稳定的。主要的限制是,除了教育,我们无法适应生活方式因素或其他无法衡量的混杂因素。结论: 在这项研究中,hrpv 阳性的女性宫颈肿瘤比 hrpv 阴性的女性预后更好。HrHPV 似乎是宫颈癌更好预后的生物标志物,独立于年龄、 FIGO 分期和组织学类型,扩展了已经确定的预后因素的信息。缺乏可检测的肿瘤 hrhvv 与相当差的预后相关的潜在生物学机制尚不清楚,应进一步研究。

cervical cancer

妇产 妇科肿瘤 疾病
概述  :  

全世界每年约50万妇女罹患宫颈癌,超过30万人死亡,高危人乳头状瘤病毒(hrHPV)持续感染是致病的元凶,大约90%的宫颈癌发生在筛查不足和HPV疫苗接种欠缺的中低收入国家。在高收入国家,30年来随着筛查的推广普及,宫颈癌的发病率和死亡率已降低一半以上,由于涉及根治性手术与放化疗,宫颈癌的疗效取决于临床期别和当地的医疗资源,保留生育功能的保守性手术已成为早期低危患者的标准治疗,适当调强放疗,宫颈癌的疗效不断改善,并发症明显减少,但转移或复发患者总体预后仍然很差,抗血管内皮生长因子药物贝伐单抗

cervical  英 ['sɜːvɪk(ə)l; sɜː'vaɪk(ə)l]  美 ['sɝvɪkl]

       adj. 颈的;子宫颈的

同根词   词根: cervix

n.cervix 子宫颈;颈部   

cervicitis [妇产] 子宫颈炎

       So, how should as treatment for cervical disease cause infertility? 那么,该如何治疗由于宫颈病变导致的不孕呢?


cancer  英 ['kænsə]  美 [kænsə]

       n. 癌症;恶性肿瘤

       What do Antioxidants have to do with cancer? 抗氧化剂对癌症的作用有哪些?

请扫描右侧二维码,免费查看词汇专业知识背景