多种高危型 HPV 与接受抗逆转录病毒治疗的乌干达 HIV 阳性女性的宫颈发育不良有关。

Multiple High-Risk HPV Types Contribute to Cervical Dysplasia in Ugandan Women Living With HIV on Antiretroviral Therapy.

机构信息

Uganda Cancer Institute, Kampala, Uganda.

Vaccine and Infectious Disease Division and Global Oncology Program, Fred Hutchinson Cancer Research Center, Seattle, WA.

出版信息

J Acquir Immune Defic Syndr. 2022 Jul 1;90(3):333-342. doi: 10.1097/QAI.0000000000002941.

DOI:10.1097/QAI.0000000000002941

PMID:35195571

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9203909/

Abstract

BACKGROUND

Cervical cancer mortality remains high in sub-Saharan Africa, especially among women living with HIV (WLWH). Characterization of prevalent high-risk human papillomavirus (hrHPV) types and immune function in WLWH with cervical abnormalities despite antiretroviral therapy (ART) can inform prevention strategies.

SETTING

Kampala, Uganda.

METHODS

From 2017 to 2020, we enrolled Ugandan women with cervical dysplasia detected with visual inspection with acetic acid (VIA). WLWH were required to be on ART >3 months with plasma HIV RNA <1000 copies/mL. Biopsies from VIA-positive lesions underwent histopathologic grading and cervical swab specimens were tested for hrHPV. Clinical correlations were evaluated with Poisson regression to estimate adjusted prevalence ratios (aPR).

RESULTS

One hundred eighty-eight WLWH and 116 HIV-seronegative women participated. Among WLWH, median ART duration was 6 years and median CD4 667 cells/µL. Cervical intraepithelial neoplasia (CIN) grade 2/3 was found in 29% of WLWH versus 9% of HIV-seronegative women. In women with CIN1 or without histopathology-confirmed dysplasia, hrHPV (aPR [95% confidence interval]: 2.17 [1.43 to 3.29]) and multiple hrHPV (aPR 3.73 [1.07 to 13.1]) were more common in WLWH, as were vaccine-targeted and vaccine-untargeted hrHPVtypes. Differences in hrHPV prevalence by HIV serostatus were not observed in women with CIN2/3 (interaction P < 0.01). Among WLWH, low CD4/8 ratio was associated with hrHPV while detectable plasma HIV RNA (20-1000 copies/mL) was associated with CIN2/3 or invasive cancer.

CONCLUSION

Despite ART, WLWH with cervical VIA abnormalities remain at elevated risk for multiple hrHPV and high-grade dysplasia. Cervical cancer prevention and research tailored for WLWH are warranted in the ART era.

摘要

背景

在撒哈拉以南非洲，宫颈癌死亡率仍然很高，尤其是在接受抗逆转录病毒治疗（ART）的艾滋病毒感染者（WHWL）中。对接受 ART 治疗但仍存在宫颈异常的 WHWL 中普遍存在的高危型人乳头瘤病毒（hrHPV）类型和免疫功能进行描述，可为预防策略提供信息。

地点

乌干达坎帕拉。

方法

2017 年至 2020 年，我们招募了通过醋酸视觉检查（VIA）发现宫颈发育不良的乌干达妇女。WHWL 必须接受 ART 治疗>3 个月，血浆 HIV RNA<1000 拷贝/ml。VIA 阳性病变的活检进行组织病理学分级，宫颈拭子标本检测 hrHPV。采用泊松回归评估临床相关性，以估计调整后的患病率比（aPR）。

结果

188 名 WHWL 和 116 名 HIV 血清阴性妇女参与了研究。WHWL 中，ART 治疗中位时间为 6 年，CD4 中位数为 667 个细胞/μL。WHWL 中发现 29%的宫颈上皮内瘤变（CIN）2/3，而 HIV 血清阴性妇女为 9%。在 CIN1 或无组织病理学证实的发育不良的妇女中，WHWL 中 hrHPV（aPR[95%置信区间]：2.17[1.43 至 3.29]）和多种 hrHPV（aPR 3.73[1.07 至 13.1]）更为常见，包括疫苗靶向和非疫苗靶向的 hrHPV 类型。在 CIN2/3 妇女中，按 HIV 血清状态划分的 hrHPV 患病率无差异（交互 P<0.01）。在 WHWL 中，低 CD4/8 比值与 hrHPV 相关，而可检测到的血浆 HIV RNA（20-1000 拷贝/ml）与 CIN2/3 或浸润性癌相关。