Clinical Research Department, London School of Hygiene & Tropical Medicine, London, UK.
MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK.
Lancet HIV. 2018 Jan;5(1):e45-e58. doi: 10.1016/S2352-3018(17)30149-2. Epub 2017 Oct 26.
BACKGROUND: The interactions between antiretroviral therapy (ART) and high-risk human papillomavirus (HPV) and cervical lesions in women living with HIV are poorly understood. We reviewed the association of ART with these outcomes. METHODS: We did a systematic review and meta-analysis by searching MEDLINE and Embase databases for cross-sectional or cohort studies published in English between Jan 1, 1996, and May 6, 2017, which reported the association of ART with prevalence of high-risk HPV or prevalence, incidence, progression, or regression of histological or cytological cervical abnormalities, or incidence of invasive cervcal cancer. Studies were eligible if they reported the association of combination ART or highly active ART use with the following outcomes: high-risk HPV prevalence; squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) prevalence, incidence, progression, or regression; and invasive cervical cancer incidence among women living with HIV. We did random-effects meta-analyses to estimate summary statistics. We examined heterogeneity with the I statistic. This review is registered on the PROSPERO database at the Centre of Reviews and Dissemination, University of York, York, UK (registration number CRD42016039546). FINDINGS: We identified 31 studies of the association of ART with prevalence of high-risk HPV (6537 women living with HIV) and high grade cervical lesions (HSIL-CIN2+; 9288 women living with HIV). Women living with HIV on ART had lower prevalence of high-risk HPV than did those not on ART (adjusted odds ratio [aOR] 0·83, 95% CI 0·70-0·99; I=51%, adjusted for CD4 cell count and ART duration), and there was some evidence of association with HSIL-CIN2+ (0·65, 0·40-1·06; I=30%). 17 studies reported the association of ART with longitudinal cervical lesion outcomes. ART was associated with a decreased risk of HSIL-CIN2+ incidence among 1830 women living with HIV (0·59, 0·40-0·87; I=0%), SIL progression among 6212 women living with HIV (adjusted hazard ratio [aHR] 0·64, 95% CI 0·54-0·75; I=18%), and increased likelihood of SIL or CIN regression among 5261 women living with HIV (1·54, 1·30-1·82; I=0%). In three studies among 15 846 women living with HIV, ART was associated with a reduction in invasive cervical cancer incidence (crude HR 0·40, 95% CI 0·18-0·87, I=33%). INTERPRETATION: Early ART initiation and sustained adherence is likely to reduce incidence and progression of SIL and CIN and ultimately incidence of invasive cervical cancer. Future cohort studies should aim to confirm this possible effect. FUNDING: UK Medical Research Council.
背景:抗逆转录病毒疗法(ART)与高危型人乳头瘤病毒(HPV)和女性 HIV 感染者的宫颈病变之间的相互作用尚未完全清楚。我们对 ART 与这些结局之间的关系进行了综述。
方法:我们通过检索 MEDLINE 和 Embase 数据库,对 1996 年 1 月 1 日至 2017 年 5 月 6 日期间发表的以英文撰写的横断面或队列研究进行了系统综述和荟萃分析,这些研究报告了 ART 与高危型 HPV 流行率,或组织学或细胞学宫颈异常的流行率、发生率、进展或消退,或侵袭性宫颈癌发病率之间的关系。如果研究报告了联合 ART 或高效抗逆转录病毒治疗(HAART)的使用与以下结局之间的关系,则这些研究符合纳入标准:高危型 HPV 流行率;鳞状上皮内病变(SIL)或宫颈上皮内瘤变(CIN)流行率、发生率、进展或消退;以及 HIV 感染者的侵袭性宫颈癌发病率。我们采用随机效应荟萃分析来估计汇总统计量。我们用 I ² 检验来评估异质性。本综述在英国约克大学综述与传播中心的 PROSPERO 数据库(注册号 CRD42016039546)中进行了注册。
发现:我们共确定了 31 项关于 ART 与高危型 HPV 流行率(6537 例 HIV 感染者)和高级别宫颈病变(HSIL-CIN2+;9288 例 HIV 感染者)关系的研究。接受 ART 的 HIV 感染者高危型 HPV 流行率低于未接受 ART 的 HIV 感染者(校正比值比[aOR]0·83,95%CI 0·70-0·99;I²=51%,校正了 CD4 细胞计数和 ART 持续时间),并且与 HSIL-CIN2+有一定的相关性(0·65,0·40-1·06;I²=30%)。17 项研究报告了 ART 与纵向宫颈病变结局之间的关系。在 1830 例 HIV 感染者中,ART 与 HSIL-CIN2+的发生率降低有关(0·59,0·40-0·87;I²=0%),在 6212 例 HIV 感染者中与 SIL 进展有关(校正危险比[aHR]0·64,95%CI 0·54-0·75;I²=18%),在 5261 例 HIV 感染者中与 SIL 或 CIN 消退的可能性增加有关(1·54,1·30-1·82;I²=0%)。在 15846 例 HIV 感染者中,有 3 项研究显示 ART 与侵袭性宫颈癌发生率降低有关(未校正 HR 0·40,95%CI 0·18-0·87,I²=33%)。
解释:早期 ART 启动和持续的依从性可能会降低 SIL 和 CIN 的发生率和进展,并最终降低侵袭性宫颈癌的发生率。未来的队列研究应旨在证实这一可能的效果。
资助:英国医学研究理事会。
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