HPV 检测在宫颈癌筛查中的效果：四项欧洲随机对照试验的随访研究。

Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials.

机构信息

Center for Cancer Epidemiology and Prevention, AO City of Health and Science, Turin, Italy.

Karolinska Institutet, Stockholm, Sweden.

出版信息

Lancet. 2014 Feb 8;383(9916):524-32. doi: 10.1016/S0140-6736(13)62218-7. Epub 2013 Nov 3.

DOI:10.1016/S0140-6736(13)62218-7

PMID:24192252

Abstract

BACKGROUND

In four randomised trials, human papillomavirus (HPV)-based screening for cervical cancer was compared with cytology-based cervical screening, and precursors of cancer were the endpoint in every trial. However, direct estimates are missing of the relative efficacy of HPV-based versus cytology-based screening for prevention of invasive cancer in women who undergo regular screening, of modifiers (eg, age) of this relative efficacy, and of the duration of protection. We did a follow-up study of the four randomised trials to investigate these outcomes.

METHODS

176,464 women aged 20-64 years were randomly assigned to HPV-based (experimental arm) or cytology-based (control arm) screening in Sweden (Swedescreen), the Netherlands (POBASCAM), England (ARTISTIC), and Italy (NTCC). We followed up these women for a median of 6·5 years (1,214,415 person-years) and identified 107 invasive cervical carcinomas by linkage with screening, pathology, and cancer registries, by masked review of histological specimens, or from reports. Cumulative and study-adjusted rate ratios (experimental vs control) were calculated for incidence of invasive cervical carcinoma.

FINDINGS

The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0·60 (95% CI 0·40-0·89), with no heterogeneity between studies (p=0·52). Detection of invasive cervical carcinoma was similar between screening methods during the first 2·5 years of follow-up (0·79, 0·46-1·36) but was significantly lower in the experimental arm thereafter (0·45, 0·25-0·81). In women with a negative screening test at entry, the rate ratio was 0·30 (0·15-0·60). The cumulative incidence of invasive cervical carcinoma in women with negative entry tests was 4·6 per 10(5) (1·1-12·1) and 8·7 per 10(5) (3·3-18·6) at 3·5 and 5·5 years, respectively, in the experimental arm, and 15·4 per 10(5) (7·9-27·0) and 36·0 per 10(5) (23·2-53·5), respectively, in the control arm. Rate ratios did not differ by cancer stage, but were lower for adenocarcinoma (0·31, 0·14-0·69) than for squamous-cell carcinoma (0·78, 0·49-1·25). The rate ratio was lowest in women aged 30-34 years (0·36, 0·14-0·94).

INTERPRETATION

HPV-based screening provides 60-70% greater protection against invasive cervical carcinomas compared with cytology. Data of large-scale randomised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years.

FUNDING

European Union, Belgian Foundation Against Cancer, KCE-Centre d'Expertise, IARC, The Netherlands Organisation for Health Research and Development, the Italian Ministry of Health.

摘要

背景

在四项随机试验中，人乳头瘤病毒（HPV）为基础的宫颈癌筛查与细胞学为基础的宫颈筛查进行了比较，并且在每一项试验中癌症前体都是终点。然而，关于 HPV 为基础的筛查与细胞学为基础的筛查对接受常规筛查的女性预防浸润性宫颈癌的相对疗效、修饰剂（如年龄）对这种相对疗效的影响，以及保护持续时间的直接估计值都还存在缺失。我们对这四项随机试验进行了随访研究，以调查这些结果。

方法

在瑞典（Swedescreen）、荷兰（POBASCAM）、英国（ARTISTIC）和意大利（NTCC），20-64 岁的 176464 名女性被随机分配接受 HPV 为基础（实验组）或细胞学为基础（对照组）的筛查。我们对这些女性进行了中位数为 6.5 年（1214415 人年）的随访，并通过与筛查、病理学和癌症登记处的关联、通过对组织学标本的盲法审查或通过报告，发现了 107 例浸润性宫颈癌。计算了累积和研究调整后的发病率比（实验组与对照组），以评估浸润性宫颈癌的发病率。

发现

从招募到随访结束，所有女性的浸润性宫颈癌发病率比为 0.60（95%CI 0.40-0.89），各研究之间没有异质性（p=0.52）。在随访的头 2.5 年内，两种筛查方法的宫颈癌检出率相似（0.79，0.46-1.36），但此后实验组的检出率明显降低（0.45，0.25-0.81）。在初筛阴性的女性中，发病率比为 0.30（0.15-0.60）。在初筛阴性的女性中，在实验组中，在 3.5 年和 5.5 年时，浸润性宫颈癌的累积发病率分别为每 10 万 5 人中有 4.6 例（1.1-12.1）和 8.7 例（3.3-18.6），而在对照组中，分别为每 10 万 5 人中有 15.4 例（7.9-27.0）和 36.0 例（23.2-53.5）。发病率比不因癌症分期而不同，但腺癌的发病率比（0.31，0.14-0.69）低于鳞癌的发病率比（0.78，0.49-1.25）。发病率比在 30-34 岁的女性中最低（0.36，0.14-0.94）。