Prevalence of cervical HPV infection in women with systemic lupus erythematosus: a systematic review and meta-analysis

Background: Human papillomavirus (HPV), a common sexually-transmitted infection, is considered a necessary cause of cervical cancer. The objectives of this systematic review and meta-regression were: 1) to compare the prevalence of cervical HPV infection between SLE patients and healthy controls and 2) to evaluate the relationship between cervical HPV infection and traditional and SLE-related risk factors for cervical HPV infection in these patients. Methods: We conducted a systematic literature review (PubMed, Cochrane library, Embase, Virtual Health Library and SciELO databases) following PRISMA guidelines and meta-regression to investigate the pooled prevalence of cervical HPV infection in adult women with SLE. The included articles were independently evaluated by two investigators who extracted information on study characteristics, defined outcomes, risk of bias and summarized strength of evidence [Quality of evidence using the Oxford Centre for evidence-based medicine (EBM) Levels of Evidence] Using meta-regression, we further analyzed whether factors such as multiple sexual partners and immunosuppressive therapy were associated with HPV prevalence. We evaluated the quality of evidence included using the Oxford Centre for evidence-based medicine (EBM) levels of evidence. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for studies providing data on HPV prevalence in women with SLE and in healthy controls. Results: A total of 687 articles were identified; 9 full-text articles examining the prevalence of cervical HPV infection in SLE women were included, comprising 751 SLE women. Eight studies employed PCR using general primers. The HPV prevalence varied from 3.1% to 80.7%. From the random effects meta-analysis, the pooled prevalence of cervical HPV infection in SLE vs. controls was 34.15% (95% CI: 19.6%-52.5%) vs. 15.3% (95% CI 0.79-27.8%), OR = 2.87 (95% CI: 2.20-3.76) p&lt; 0.0001, with large between-study heterogeneity (I2= 95.4%). When only SLE women were evaluated, meta-regression showed no significant differences between patients with and without a background of multiple sexual partners and any immunosuppressive therapy. In addition, the prevalence of cervical HPV infection did not significantly differ between SLE patients on azathioprine or cyclophosphamide. A detailed dataset presenting the totally of the articles included is attached. The variables included are the result of two datasets constructed by two independently reviewers (CMP and MGC) after resolving disagreements by consensus. The variables included in the attached file are: first author, year of publication, country where the study was carried out, study design, the number of SLE patients and/or controls, their mean age, glucocorticoid use and dose in SLE participants as well as immunosuppressant, increased number of sexual partners, method sample collection, HPV detection method, HPV genotype and HPV high risk prevalence"背景：人乳头瘤病毒（Human papillomavirus, HPV）是一种常见的性传播感染病原体，被认为是宫颈癌发生的必要致病因素。本系统评价与Meta回归分析的研究目的包括：1) 对比系统性红斑狼疮（Systemic Lupus Erythematosus, SLE）患者与健康对照人群的宫颈HPV感染患病率；2) 探究该人群中宫颈HPV感染与传统宫颈癌危险因素以及与SLE相关的宫颈HPV感染危险因素之间的关联。 研究方法：本研究遵循PRISMA指南，通过系统文献检索（涵盖PubMed、Cochrane图书馆、Embase、虚拟健康图书馆（Virtual Health Library）及SciELO数据库）结合Meta回归分析，旨在探究成年SLE女性的宫颈HPV感染合并患病率。纳入的文献由两名研究者独立进行质量评价，并提取研究特征、结局定义、偏倚风险及证据强度相关信息[证据质量采用牛津循证医学中心（Oxford Centre for Evidence-Based Medicine, EBM）证据分级标准]。通过Meta回归分析，本研究进一步分析了多个性伴侣、免疫抑制治疗等因素是否与HPV感染患病率存在关联。本研究采用牛津循证医学中心证据分级标准对纳入文献的证据质量进行评价。针对提供了SLE女性及健康对照人群HPV感染患病率数据的研究，本研究计算了合并比值比（OR）及95%置信区间（CI）。 研究结果：本研究共检索到687篇文献，最终纳入9篇探讨SLE女性宫颈HPV感染患病率的全文文献，共计纳入751名SLE患者。其中8项研究采用通用引物聚合酶链反应（Polymerase Chain Reaction, PCR）进行HPV检测。宫颈HPV感染患病率的范围为3.1%至80.7%。随机效应Meta分析结果显示，SLE组与对照组的宫颈HPV感染合并患病率分别为34.15%（95%CI：19.6%~52.5%）与15.3%（95%CI：0.79%~27.8%），合并比值比OR=2.87（95%CI：2.20~3.76），p<0.0001，且各研究间存在显著异质性（I²=95.4%）。仅针对SLE女性人群的Meta回归分析显示，有无多个性伴侣史及免疫抑制治疗史的患者之间，HPV感染患病率无显著差异。此外，接受硫唑嘌呤或环磷酰胺治疗的SLE患者，其宫颈HPV感染患病率亦无显著差异。本研究附有所纳入全部文献的详细数据集。该数据集由两名独立评审员（CMP与MGC）在通过共识解决分歧后构建，包含两个独立评审组生成的变量信息。附件文件中包含的变量如下：第一作者、发表年份、研究开展国家、研究设计、SLE患者及/或对照人群的样本量、研究人群的平均年龄、SLE参与者的糖皮质激素使用情况及给药剂量、免疫抑制剂使用情况、性伴侣数量增加情况、样本采集方法、HPV检测方法、HPV基因型及高危型HPV感染患病率