尼日利亚中北部地区宫颈癌前病变和宫颈癌中阴道微生物组群落状态类型与高危型人乳头瘤病毒。
Vaginal microbiome community state types and high-risk human papillomaviruses in cervical precancer and cancer in North-central Nigeria.
机构信息
Department of Obstetrics and Gynecology, College of Health Sciences, University of Jos, Jos, Plateau State, Nigeria.
Department of Preventive Medicine, Division of Cancer Epidemiology and Prevention, Feinberg School of Medicine, Northwestern University, Chicago, USA.
出版信息
BMC Cancer. 2023 Jul 20;23(1):683. doi: 10.1186/s12885-023-11187-5.
BACKGROUND
High risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC).
METHODS
This was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (Anyplex™ II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16 S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC.
RESULTS
We enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43-58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p = 0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR = 1.13, CST-IV aOR = 1.31). However, in the presence of HR-HPV CST-III (aOR = 6.7) and CST-IV (aOR = 3.6) showed positive association with HSIL/ICC.
CONCLUSION
Vaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control.
背景
高危型人乳头瘤病毒（HR-HPV）在宫颈癌的发生中起因果作用，而 HIV 介导的免疫抑制允许 HR-HPV 持续存在。我们研究了阴道微生物组群落状态类型（CST）是否与高级别癌前病变和/或浸润性宫颈癌（HSIL/ICC）相关。
方法
这是一项在尼日利亚乔斯大学教学医院（JUTH）进行的宫颈癌筛查（CCS）成年女性的横断面研究，时间为 2020 年 1 月至 2022 年 2 月。宫颈拭子进行 HPV 基因分型（Anyplex ™ II HPV28）。采集宫颈阴道灌洗液（CVL）样本进行 16S rRNA 基因扩增子测序。我们使用多变量逻辑回归模型评估 CST 与其他与 HSIL/ICC 相关的因素之间的关联。
结果
我们纳入了 155 名符合条件的参与者，其中 151 名有微生物组数据进行了此项分析。女性中位年龄为 52 岁（IQR：43-58），47.7%HIV 阳性，58.1%有 HSIL/ICC。在 138 名有 HPV 数据的女性中，40.6%HPV 阴性，10.1%低危 HPV，26.8%单一 HR-HPV，22.5%多种 HR-HPV 类型。任何 HR-HPV 类型（单一和多种）的总体流行率为 49.3%，HSIL/ICC 女性中比例更高（NILM 31.6%，LSIL 46.5%，HSIL 40.8%，ICC 81.5%；p=0.007）。HIV 阳性女性更有可能患有 HSIL/ICC（70.3%比 HIV 阴性女性的 29.7%）。在未校正和多变量分析中，CST 与宫颈癌病理无关联（CST-III 的优势比[aOR]=1.13，CST-IV 的 aOR=1.31）。然而，在存在 HR-HPV 的情况下，CST-III（aOR=6.7）和 CST-IV（aOR=3.6）与 HSIL/ICC 呈阳性关联。
结论
阴道微生物组 CST 与 HSIL/ICC 无显著相关性。然而，我们的研究结果表明，CST 可能有助于识别 HSIL/ICC 女性，特别是 HR-HPV 阳性女性。在 HR-HPV 女性中使用即时分子检测对 CST 进行特征描述，应作为提高早期检测和宫颈癌预防的一种方法进行研究。未来的纵向研究将提高我们对非最佳 CST、HR-HPV 和宫颈癌发生、预防和控制其他因素的时间效应的理解。
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