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高危型人乳头瘤病毒(Human papillomavirus,HPV)持续感染可导致癌前病变,以HPV-16/HPV-18型感染最为常见,但HPV感染所产生的中和抗体(Neutralizing Antibody,nAb)对宫颈癌及癌前病变的相关关系尚不明确。本研究旨在探索HPV-16/HPV-18在不同的中和抗体与DNA感染状态下的年龄分布及其和宫颈组织学病变的相关性。通过横断面研究,本研究于2012年11月至2013年4月招募7 372名18～45岁健康女性。收集每个受试者血清用假病毒中和抗体定性检测HPV-16和HPV-18中和抗体;采集宫颈细胞学样本用于液基细胞学诊断,并用HPV SPF10PCR-DEIA-LiPA25分型检测系统及HPV-16/HPV-18型特异性DNA酶联免疫测定法联合检测HPV-16/HPV-18 DNA;召回细胞学异常的受试者在阴道镜下采集组织学标本进行病理诊断。结果显示,HPV-16和HPV-18中和抗体(nAb)阳性率为12.56%,4.94%,DNA阳性率为2.69%和0.92%,nAb与DNA的一致率较低。HPV-16和HPV-18DNA-/nAb+人群在27～45岁的大龄组女性中比例均高于18～26岁女性。DNA+/nAb+和DNA+/nAb-人群在18～26岁和27～45岁年龄组中比例无统计学差异。多因素分析结果显示,与DNA-/nAb-人群相比,HPV-16 DNA+/nAb-人群发生宫颈高度病变CIN2+的风险较高,而DNA+/nAb+则风险更高,调整OR分别为33.80(95%CI:16.50～69.23)和63.86(95%CI:36.57～111.52);HPV-18呈现相同的规律,调整OR分别为5.39(95%CI:1.14～25.56)和7.83(1.61～38.14)。HPV-16或HPV-18 DNA阳性的女性是宫颈组织学病变的高危人群,而若DNA阳性伴有同型抗体阳性的人群则风险更高,这对于探究宫颈病变的自然发病机理具有一定意义。
Abstract：Persistent infection by high-risk human papillomavirus(HPV)can lead to precancerous lesions,and HPV - 16/HPV - 18 infection is most common. However,the association of neutralizing antibody(nAb)produced by HPV infection in the prognosis of cervical cancer is not conclusive. We explored the correlation between different extents of HPV - 16/HPV - 18 infection(based on nAb and DNA) with cervical lesions assessed by histology. In this cross-sectional study,7372 healthy women aged 18 ～45 years were recruited from November 2012 to April 2013. Serum samples from each participant were collected to measure HPV - 16 and HPV - 18 nAbs using a pseudovirion - based neutralization assay(PBNA). Samples of cervical cells were collected for the ThinprepTM cytologic test and HPV-16/HPV-18 genotyping test based on the HPV SPF10 PCR-DEIA-LiPA25 typing system and HPV-16/HPV-18 type-specific DNA enzyme-linked immunoassay(TS-16/TS-18 DEIA). Women with abnormal cytology were recalled and their histology specimens were collected by colposcopy for a pathological diagnosis following the protocol of clinical trials. The seroprevalence of HPV -16 and HPV -18 nAbs was 12.56% and 4.94%,and the positive rates of HPV -16 and 18 DNA was 2.69% and0.92% respectively. and the consistency between HPV nAb and DNA was poor. The proportion of HPV-16 and HPV-18 DNA-/nAb+ was higher in women aged 27～45 years than that for women aged 18～26 years. The proportion of HPV-16 DNA+/nAb+ and DNA+/nAb- in age groups of 18～26 years and 27～45 years was similar. Multivariate analyses showed that women with HPV 16 DNA+/nAb - carried a higher risk of progressing to cervical lesions known as CIN1+ and CIN2+ compared with that of women with DNA-/nAb-,whereas women with DNA+/nAb+ were at an even higher risk,with adjusted ORs of 33.80(95%CI:16.50～69.23)and 63.86(95%CI:36.57～111.52),respectively. For HPV-18,the adjusted ORs were 5.39(95%CI:1.14～25.56)and 7.83(1.61～38.14),respectively. Women who were positive for HPV-16 or HPV-18 DNA had a high risk of contracting cervical lesions based on histology,whereas those who were positive for DNA and homeotypic antibody bore a higher risk,and merit more attention. Our study is important for understanding the natural pathogenesis of cervical lesions
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.004058
中图分类号:R737.33
引用信息:
[1]胡芳芳,姚星妹,阴建,等.HPV-16/18血清中和抗体阳性率及其与宫颈病变相关性研究[J].病毒学报,2021,37(06):1355-1362.DOI:10.13242/j.cnki.bingduxuebao.004058.
基金信息:
国家自然科学基金（项目号：82073562），题目：高危型HPV自然感染者抗体产生、持续、消除的动力学及临床意义研究~~
2021-03-04
2021
2021-04-12
2021-10-25
2021
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2021-10-25
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