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| 宫颈尖锐湿疣患者HPV分布与阴道微生态及Treg/Th17免疫失衡的关联 |
| Association between HPV distribution, vaginal microecology, and Treg/Th17 immune imbalance in patients with cervical condyloma acuminatum |
| 投稿时间：2025-11-05 |
| DOI：10.3969/j.issn.1000-0399.2026.09.006 |
| 中文关键词: 尖锐湿疣 乳头状瘤病毒科 阴道微生态 T淋巴细胞 免疫失衡 |
| 英文关键词: Condyloma acuminatum Papillomaviridae Vagina microecology T lymphocytes Immune imbalance |
| 基金项目:秦皇岛市科学技术研究与发展计划(编号:202301A087) |
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| 中文摘要: |
| 目的 探讨宫颈尖锐湿疣（CA）患者人乳头瘤病毒（HPV）的感染分布特征，并分析其与阴道微生态及外周血调节性T细胞（Treg）/辅助性T细胞17(Th17)免疫平衡的关系。方法 选取2022年12月至2024年12月秦皇岛市妇幼保健院收治的157例宫颈CA患者，检测其宫颈组织23种HPV亚型，根据HPV分型将HPV阳性患者分为低危型、高危型及混合型组，并根据病毒载量将HPV阳性患者分为高载量组、中载量组和低载量组。比较各组HPV亚型、阴道微生态指标[（过氧化氢、唾液酸苷酶、白细胞酯酶、脯氨酸氨基肽酶、乙酰胺基葡萄糖苷酶、乳酸杆菌形态与数量、清洁度及菌群多样性、细菌性阴道病（BV）、滴虫性阴道炎（TV）、外阴阴道假丝酵母菌病（VVC）]及外周血Treg/Th17细胞相关因子[Treg、Th17、转化生长因子-β(TGF-β)、白细胞介素-17(IL-17)、叉头框蛋白P3(Foxp3)mRNA、维甲酸相关孤儿受体γt(RORγt)mRNA]水平差异。采用Pearson相关分析不同HPV病毒载量与外周血Treg/Th17细胞相关因子的关系。结果 157例宫颈CA患者中，HPV阳性150例（95.54%），其中低危型组118例、高危型组6例、混合型组26例；高载量79例、中载量31例、低载量40例；另7例HPV阴性未纳入后续亚组分析。与低危型相比，混合型患者的过氧化氢阳性、白细胞酯酶阳性、唾液酸苷酶阳性、清洁度Ⅲ～Ⅳ、乳酸杆菌（中大量）比例、酸碱度>4.5、BV阳性、TV阳性比例均升高（P均<0.05）。与低危型患者相比，高危型或混合型患者外周血中Treg细胞比例、TGF-β、Foxp3及Treg/Th17水平升高（P<0.05）,Th17细胞比例、IL-17、RORγt水平降低（P<0.05）；与高危型患者相比，混合型患者外周血中Treg细胞比例、TGF-β、Foxp3及Treg/Th17水平升高（P<0.05）,Th17细胞比例、IL-17、RORγt水平降低（P<0.05）。与低载量组患者相比，中载量组和高载量组患者外周血中Treg细胞比例、TGF-β、Foxp3及Treg/Th17水平升高（P<0.05）,Th17细胞比例、IL-17、RORγt水平降低（P<0.05）；与中载量组患者相比，高载量组患者Treg、TGF-β、Foxp3及Treg/Th17水平进一步升高（P<0.05）,Th17、IL-17、RORγt水平进一步降低（P<0.05）。Pearson相关性结果显示，Treg、TGF-β、Foxp3水平及Treg/Th17与HPV感染严重程度呈正相关（r=0.743、0.749、0.740、0.780,P均<0.05）,Th17、IL-17、RORγt水平与HPV感染严重程度呈负相关（r=-0.424、-0.713、-0.612,P均<0.05）。结论 宫颈CA患者高危型尤其是混合型HPV感染与更严重的阴道微生态紊乱及外周血Treg/Th17细胞免疫失衡密切相关，且免疫失衡程度随病毒载量升高而加剧，提示HPV感染、微环境与细胞免疫在CA发病中存在相互作用。 |
| 英文摘要: |
| Objective To investigate the distribution characteristics of human papillomavirus(HPV) infection in patients with cervical condyloma acuminatum(CA) and to analyze its relationship with vaginal microecology and peripheral blood regulatory T cells(Treg)/T helper 17 cells(Th17) immune balance. Methods A total of 157 patients with cervical CA admitted to Qinhuangdao Maternal and Child Health Hospital from December 2022 to December 2024 were enrolled. Twenty-three HPV subtypes in cervical tissues were detected. HPV-positive patients were divided into low-risk, high-risk, and mixed-risk groups based on HPV genotyping, and into high-load, medium-load, and lowload groups according to viral load. HPV subtypes, vaginal microecological parameters [hydrogen peroxide, sialidase, leukocyte esterase, proline aminopeptidase, N-acetyl-β-D-glucosaminidase, Lactobacillus morphology and quantity, vaginal cleanliness and microbial diversity, bacterial vaginosis(BV), trichomonal vaginitis(TV), and vulvovaginal candidiasis(VVC)], and peripheral blood Treg/Th17 cell-related factors [Treg, Th17, transforming growth factor-β(TGF-β), interleukin-17(IL-17), forkhead box protein P3(Foxp3) mRNA, and retinoic acid-related orphan receptor γt(RORγt) mRNA] were compared among groups. Pearson correlation analysis was used to evaluate the relationship between HPV viral load and peripheral blood Treg/Th17 cell-related factors. Results Among 157 patients with cervical CA, 150(95.54%) tested positive for HPV, including 118 cases in the low-risk group, 6 in the high-risk group, and 26 in the mixed-risk group; 79 cases in the high-load group, 31 in the medium-load group, and 40 in the low-load group; the remaining 7 HPV-negative patients were excluded from subsequent subgroup analyses. Compared with the low-risk group, the mixed-risk group showed significantly higher proportions of hydrogen peroxide positivity, leukocyte esterase positivity, sialidase positivity, vaginal cleanliness grade Ⅲ-Ⅳ, pH > 4.5, BV positivity, and TV positivity(all P < 0.05), while the proportion of moderate-to-high Lactobacillus abundance was significantly lower(P < 0.05). Compared with the low-risk group, patients in the high-risk or mixed-risk group exhibited significantly increased levels of Treg cell proportion, TGF-β, Foxp3, and Treg/Th17 ratio(all P < 0.05), and significantly decreased levels of Th17 cell proportion, IL-17, and RORγt(all P < 0.05). Compared with the high-risk group, the mixed-risk group showed further significant increases in Treg cell proportion, TGF-β, Foxp3, and Treg/Th17 ratio(all P < 0.05), and further significant decreases in Th17 cell proportion, IL-17, and RORγt(all P < 0.05). Compared with the low-load group, patients in the medium-load and high-load groups showed significantly increased levels of Treg cell proportion, TGF-β, Foxp3, and Treg/Th17 ratio(all P < 0.05), and significantly decreased levels of Th17 cell proportion, IL-17, and RORγt(all P < 0.05). Compared with the medium-load group, the high-load group exhibited further significant increases in Treg, TGF-β, Foxp3, and Treg/Th17 ratio(all P < 0.05), and further significant decreases in Th17, IL-17, and RORγt(all P < 0.05). Pearson correlation analysis showed that Treg, TGF-β, Foxp3, and Treg/Th17 ratio were positively correlated with the severity of HPV infection(r = 0.743, 0.749, 0.740, and 0.780, respectively, all P < 0.05), while Th17, IL-17, and RORγt were negatively correlated with the severity of HPV infection(r =-0.424,-0.713, and-0.612, respectively, all P < 0.05). Conclusion High-risk HPV infection, especially mixed HPV infection, is closely associated with more severe vaginal microecological disorders and peripheral blood Treg/Th17 immune imbalance in patients with cervical CA, and the degree of immune imbalance intensifies with increasing viral load, suggesting that HPV infection, microenvironment, and cellular immunity interact in the pathogenesis of CA. |
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