Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University, Al-Saray Street, Al-Manial, Cairo, 11562, Egypt.
Departmet of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Virol J. 2024 Aug 2;21(1):173. doi: 10.1186/s12985-024-02435-6.
Nitric oxide (NO) may contribute to the persistence of high-risk human papillomavirus (hrHPV) infection, which has been linked to the development of premalignant lesions and cervical cancer. Our study aimed to examine the relationship between cervical NO metabolite (NOx) levels, hrHPV infection, and cytopathological findings. Additionally, we assessed cervical NOx levels as a biomarker for predicting hrHPV infection and epithelial atypia.
The study involved 74 women who attended the Gynecology and Obstetrics outpatient clinics at Cairo University Hospitals between November 2021 and August 2022. Cervical samples were subjected to Pap testing, assessment of NOx levels by the Griess method, and detection of hrHPV DNA by real-time polymerase chain reaction.
High-risk HPV was detected in 37.8% of women. EA was found in 17.1% of cases, with a higher percentage among hrHPV-positive than negative cases (35.7% vs. 4.3%, p = 0.001). The most prevalent hrHPV genotype was HPV 16 (89.3%). The cervical NOx level in hrHPV-positive cases was significantly higher (37.4 µmol/mL, IQR: 34.5-45.8) compared to negative cases (2.3 µmol/mL, IQR: 1.2-9.8) (p = < 0.001). Patients with high-grade atypia showed significantly higher NOx levels (38.0 µmol/mL, IQR: 24.6-94.7) in comparison to NILM and low-grade atypia cases (5.0 µmol/mL, IQR: 1.6-33.3 and 34.5 µmol/mL, IQR: 11.7-61.7, respectively) (p = 0.006). Although the NOx levels among hrHPV-positive cases with low-grade atypia (40.4 µmol/mL, IQR: 33.3‒61.8) were higher than those with NILM (36.2 µmol/mL, IQR: 35.7‒44.0) and high-grade atypia (38.0 µmol/mL, IQR: 24.6‒94.7), the difference was not significant (p = 0.771). ROC curve analysis indicated that the cervical NOx cut-off values of > 23.61 µmol/mL and > 11.35 µmol/mL exhibited good diagnostic accuracy for the prediction of hrHPV infection and EA, respectively.
The high prevalence of hrHPV infection, particularly HPV 16, in our hospital warrants targeted treatment and comprehensive screening. Elevated cervical NOx levels are associated with hrHPV infection and high-grade atypia, suggesting their potential use as biomarkers for predicting the presence of hrHPV and abnormal cytological changes.
一氧化氮（NO）可能与高危型人乳头瘤病毒（hrHPV）感染的持续存在有关，而后者与癌前病变和宫颈癌的发展有关。本研究旨在探讨宫颈 NO 代谢产物（NOx）水平与 hrHPV 感染和细胞病理学发现之间的关系。此外，我们评估了宫颈 NOx 水平作为预测 hrHPV 感染和上皮内瘤变的生物标志物。
该研究纳入了 2021 年 11 月至 2022 年 8 月期间在开罗大学医院妇科和产科门诊就诊的 74 名女性。对宫颈样本进行巴氏涂片检查、采用格里斯法检测 NOx 水平，并通过实时聚合酶链反应检测 hrHPV DNA。
37.8%的女性检测出高危 HPV。EA 在 17.1%的病例中发现，hrHPV 阳性病例中的百分比高于阴性病例（35.7%比 4.3%，p=0.001）。最常见的 hrHPV 基因型是 HPV 16（89.3%）。hrHPV 阳性病例的宫颈 NOx 水平明显更高（37.4µmol/mL，IQR：34.5-45.8），而阴性病例的宫颈 NOx 水平较低（2.3µmol/mL，IQR：1.2-9.8）（p<0.001）。与 NILM 和低级别上皮内瘤变病例相比，高级别上皮内瘤变患者的 NOx 水平（38.0µmol/mL，IQR：24.6-94.7）显著更高（5.0µmol/mL，IQR：1.6-33.3 和 34.5µmol/mL，IQR：11.7-61.7）（p=0.006）。尽管低级别上皮内瘤变的 hrHPV 阳性病例的 NOx 水平（40.4µmol/mL，IQR：33.3-61.8）高于 NILM（36.2µmol/mL，IQR：35.7-44.0）和高级别上皮内瘤变病例（38.0µmol/mL，IQR：24.6-94.7），但差异无统计学意义（p=0.771）。ROC 曲线分析表明，宫颈 NOx 截断值 >23.61µmol/mL 和 >11.35µmol/mL 分别对预测 hrHPV 感染和 EA 具有良好的诊断准确性。
本研究中，高危型 HPV 感染，尤其是 HPV 16 感染的高发生率，需要针对性治疗和综合筛查。宫颈 NOx 水平升高与 hrHPV 感染和高级别上皮内瘤变相关，提示其作为预测 hrHPV 存在和异常细胞学改变的生物标志物具有一定的应用潜力。
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