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人类免疫缺陷病毒1型(HIV-1)阳性女性的年龄、绝对CD4细胞计数、CD4百分比与HPV感染及宫颈疾病分期的关系。

Age, absolute CD4 count, and CD4 percentage in relation to HPV infection and the stage of cervical disease in HIV-1-positive women.

作者信息

Chambuso Ramadhani, Ramesar Raj, Kaambo Evelyn, Murahwa Alltalents T, Abdallah Mohammed O E, De Sousa Michelle, Denny Lynette, Williamson Anna-Lise, Gray Clive M

机构信息

MRC Unit for Genomic and Precision Medicine, Division of Human Genetics, Department of Pathology.

Department of Gynaecology, Morogoro Regional Referral Hospital, Morogoro, Tanzania.

出版信息

Medicine (Baltimore). 2020 Feb;99(9):e19273. doi: 10.1097/MD.0000000000019273.

Abstract

A subgroup of women who are co-infected with human immunodeficiency virus type 1 (HIV-1) and human papillomavirus (HPV), progress rapidly to cervical disease. We characterized HPV genotypes within cervical tumor biopsies, assessed the relationships of cervical disease stage with age, HIV-1 status, absolute CD4 count, and CD4 percentage, and identified the predictive power of these variables for cervical disease stage in a cohort of South African women.We recruited 181 women who were histologically diagnosed with cervical disease; 87 were HIV-1-positive and 94 were HIV-1-seronegative. Colposcopy-directed tumor biopsies were confirmed by histology and used for genomic DNA extraction. The Roche Linear Array HPV genotyping test was used for HPV genotyping. Peripheral whole blood was used for HIV-1 rapid testing. Fully automated FC500MPL/CellMek with PanLeucogate (PLG) was used to determine absolute CD4 count, CD4 percentage, and CD45 count. Chi-squared test, a logistic regression model, parametric Pearson correlation, and ROC curves were used for statistical analyses. We used the Benjamini-Horchberg test to control for false discovery rate (FDR, q-value). All tests were significant when both P and q were <.05.Age was a significant predictor for invasive cervical cancer (ICC) in both HIV-1-seronegative (P < .0001, q < 0.0001) and HIV-1-positive women (P = .0003, q = 0.0003). Sixty eight percent (59/87) of HIV-1-positive women with different stages of cervical disease presented with a CD4 percentage equal or less than 28%, and a median absolute CD4 count of 400 cells/μl (IQR 300-500 cells/μl). Of the HIV-1-positive women, 75% (30/40) with ICC, possessed ≤28% CD4 cells vs 25% (10/40) who possessed >28% CD4 cells (both P < .001, q < 0.001). Furthermore, 70% (28/40) of women with ICC possessed CD4 count >350 compared to 30% (12/40) who possessed CD4 count ≤ 350 (both P < .001, q < 0.001).Age is an independent predictor for ICC. In turn, development of ICC in HIV-1-positive women is independent of the host CD4 cells and associates with low CD4 percentage regardless of absolute CD4 count that falls within the normal range. Thus, using CD4 percentage may add a better prognostic indicator of cervical disease stage than absolute CD4 count alone.

摘要

一小部分同时感染1型人类免疫缺陷病毒(HIV-1)和人乳头瘤病毒(HPV)的女性会迅速发展为宫颈疾病。我们对宫颈肿瘤活检组织中的HPV基因型进行了特征分析,评估了宫颈疾病分期与年龄、HIV-1感染状况、绝对CD4细胞计数及CD4百分比之间的关系,并在一组南非女性队列中确定了这些变量对宫颈疾病分期的预测能力。我们招募了181名经组织学诊断患有宫颈疾病的女性;其中87名HIV-1阳性,94名HIV-1血清阴性。阴道镜引导下的肿瘤活检经组织学确认后用于基因组DNA提取。采用罗氏线性阵列HPV基因分型检测进行HPV基因分型。外周全血用于HIV-1快速检测。使用配备全白细胞门控(PLG)的全自动FC500MPL/CellMek测定绝对CD4细胞计数、CD4百分比和CD45计数。采用卡方检验、逻辑回归模型、参数Pearson相关性分析和ROC曲线进行统计分析。我们使用Benjamini-Horchberg检验来控制错误发现率(FDR,q值)。当P和q均<.05时,所有检验均具有统计学意义。年龄是HIV-1血清阴性(P<.0001,q<0.0001)和HIV-1阳性女性(P = 0.0003,q = 0.0003)发生浸润性宫颈癌(ICC)的显著预测因素。87名处于不同宫颈疾病阶段的HIV-1阳性女性中,68%(59/87)的CD4百分比等于或低于28%,绝对CD4细胞计数中位数为400个/μl(四分位间距300 - 500个/μl)。在HIV-1阳性女性中,75%(30/40)的ICC患者CD4细胞≤28%,而CD4细胞>28%的患者占25%(10/40)(两者P<.001,q<0.001)。此外,70%(28/40)的ICC女性CD4细胞计数>350,而CD4细胞计数≤350的女性占30%(12/40)(两者P<.001,q<0.001)。年龄是ICC的独立预测因素。反过来,HIV-1阳性女性发生ICC与宿主CD4细胞无关,且无论绝对CD4细胞计数是否在正常范围内,均与低CD4百分比相关。因此,使用CD4百分比可能比单独使用绝对CD4细胞计数能更好地预测宫颈疾病分期。

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