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针对宫颈癌高危非接种女性血清和宫颈阴道 IgG 对 α7 和 α9 HPV 的免疫应答:对补种预防性 HPV 疫苗接种的启示。

Serum and cervicovaginal IgG immune responses against α7 and α9 HPV in non-vaccinated women at risk for cervical cancer: Implication for catch-up prophylactic HPV vaccination.

机构信息

Laboratoire de virologie, hôpital européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.

Ecole Doctorale Régionale en Infectiologie Tropicale, Franceville, Gabon.

出版信息

PLoS One. 2020 May 18;15(5):e0233084. doi: 10.1371/journal.pone.0233084. eCollection 2020.

Abstract

BACKGROUND

Cervical cancer associated with high risk-human papillomavirus (HR-HPV) infection is becoming the one of the most common female cancer in many sub-Saharan African countries. First-generation immigrant African women living in Europe are at-risk for cervical cancer, in a context of social vulnerability, with frequent lack of cervical cancer screening and HPV vaccination.

OBJECTIVE

Our objective was to address immunologically the issue of catch-up prophylactic HPV vaccination in first-generation African immigrant women living in France.

METHODS

IgG immune responses and cross-reactivities to α7 (HPV-18, -45 and -68) and α9 (HPV-16, -31, -33, -35, -52 and -58) HPV types, including 7 HR-HPV targeted by the Gardasil-9® prophylactic vaccine, were evaluated in paired serum and cervicovaginal secretions (CVS) by HPV L1-virus-like particles-based ELISA. Genital HPV were detected by multiplex real time PCR (Seegene, Seoul, South Korea).

RESULTS

Fifty-one immigrant women (mean age, 41.7 years; 72.5% HIV-infected) were prospectively included. More than two-third (68.6%) of them carried genital HPV (group I) while 31.4% were negative (group II). The majority (90.2%) exhibited serum IgG to at least one α7/α9 HR-HPV. Serum HPV-specific IgG were more frequently detected in group I than group II (100% versus 68.7%; P = 0.002). The distribution of serum and genital HPV-specific IgG was similar, but mean number of IgG reactivities to α7/α9 HR-HPV was higher in serum than CVS (5.6 IgG per woman in serum versus 3.2 in CVS; P<0.001). Rates of IgG cross-reactivities against HPV different from detected cervicovaginal HPV were higher in serum and CVS in group I than group II. Finally, the majority of groups I and II women (68.6% and 68.7%, respectively) exhibited serum or cervicovaginal IgG to Gardasil-9® HR-HPV, with higher mean rates in group I than group II (6.1 Gardasil-9® HR-HPV per woman versus 1.4; P<0.01). One-third (31.2%) of group II women did not show any serum and genital HPV-specific IgG.

CONCLUSIONS

Around two-third of first-generation African immigrant women living in France showed frequent ongoing genital HPV infection and high rates of circulating and genital IgG to α7/α9 HPV, generally cross-reacting, avoiding the possibility of catch-up vaccination. Nevertheless, about one-third of women had no evidence of previous HPV infection, or showed only low levels of genital and circulating HR-HPV-specific IgG and could therefore be eligible for catch-up vaccination.

摘要

背景

在许多撒哈拉以南非洲国家,宫颈癌与高危型人乳头瘤病毒(HR-HPV)感染有关,已成为最常见的女性癌症之一。生活在欧洲的第一代非洲移民女性面临宫颈癌风险,她们处于社会弱势地位,经常缺乏宫颈癌筛查和 HPV 疫苗接种。

目的

我们旨在从免疫学角度解决生活在法国的第一代非洲移民女性进行 HPV 疫苗补种的问题。

方法

通过 HPV L1-病毒样颗粒 ELISA 评估配对血清和宫颈阴道分泌物(CVS)中针对 α7(HPV-18、-45 和 -68)和 α9(HPV-16、-31、-33、-35、-52 和 -58)HPV 类型的 IgG 免疫反应和交叉反应性,包括 Gardasil-9®预防性疫苗针对的 7 种 HR-HPV。通过多重实时 PCR(韩国首尔的 Seegene)检测生殖道 HPV。

结果

前瞻性纳入 51 名移民女性(平均年龄 41.7 岁;72.5%感染 HIV)。其中超过三分之二(68.6%)的人携带生殖道 HPV(I 组),31.4%的人呈阴性(II 组)。大多数(90.2%)女性血清中至少存在一种针对 α7/α9 HR-HPV 的 IgG。I 组血清 HPV 特异性 IgG 的检出率高于 II 组(100%比 68.7%;P=0.002)。血清和生殖道 HPV 特异性 IgG 的分布相似,但血清中针对 α7/α9 HR-HPV 的 IgG 反应数量高于 CVS(5.6 种 IgG/名女性在血清中,3.2 种在 CVS 中;P<0.001)。I 组血清和 CVS 中针对不同生殖道 HPV 的 IgG 交叉反应率高于 II 组。最后,大多数 I 组和 II 组女性(分别为 68.6%和 68.7%)血清或 CVS 中存在针对 Gardasil-9®HR-HPV 的 IgG,I 组的平均水平高于 II 组(6.1 种 Gardasil-9®HR-HPV/名女性比 1.4;P<0.01)。三分之一(31.2%)的 II 组女性未检测到任何血清和生殖道 HPV 特异性 IgG。

结论

生活在法国的第一代非洲移民女性中,约有三分之二经常发生生殖道 HPV 感染,循环和生殖道 α7/α9 HPV 的 IgG 水平较高,通常发生交叉反应,排除了 HPV 补种的可能性。然而,约三分之一的女性没有 HPV 感染的证据,或仅表现出低水平的生殖道和循环 HR-HPV 特异性 IgG,因此可以有资格进行补种。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7900/7233543/db17acc7dc54/pone.0233084.g001.jpg

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