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Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：一氧化氮（NO）可能有助于高危型人乳头瘤病毒（hrHPV）感染的持续存在，这与癌前病变和宫颈癌的发展有关。我们的研究旨在检查宫颈NO代谢物（NOx）水平之间的关系，hrHPV感染，和细胞病理学发现。此外,我们评估了宫颈NOx水平作为预测hrHPV感染和上皮异型性的生物标志物.
方法：该研究涉及2021年11月至2022年8月在开罗大学医院妇产科门诊就诊的74名女性。宫颈样本进行巴氏试验，用格里斯方法评估NOx水平，并通过实时聚合酶链反应检测hrHPVDNA。
结果：在37.8%的女性中检测到高危型HPV。在17.1%的病例中发现了EA，hrHPV阳性病例中的百分比高于阴性病例(35.7%vs.4.3%,p=0.001)。最普遍的hrHPV基因型是HPV16(89.3%)。hrHPV阳性病例的宫颈NOx水平明显较高（37.4µmol/mL，IQR：34.5-45.8）与阴性病例（2.3µmol/mL，IQR：1.2-9.8）（p=<0.001）。高度非典型性患者的NOx水平显着升高（38.0µmol/mL，IQR：24.6-94.7）与NILM和低度非典型病例（5.0µmol/mL，IQR：1.6-33.3和34.5µmol/mL，IQR：分别为11.7-61.7）（p=0.006）。尽管在低级别异型的hrHPV阳性病例中NOx水平（40.4µmol/mL，IQR：33.3-61.8）高于NILM（36.2µmol/mL，IQR：35.7–44.0）和高级非典型性（38.0µmol/mL，IQR：24.6–94.7），差异无统计学意义(p=0.771)。ROC曲线分析表明，>23.61µmol/mL和>11.35µmol/mL的宫颈NOx临界值对预测hrHPV感染和EA具有良好的诊断准确性。分别。
结论：hrHPV感染率高，特别是HPV16，在我们医院需要有针对性的治疗和全面的筛查。宫颈NOx水平升高与hrHPV感染和高度非典型性相关，提示它们可能用作预测hrHPV存在和异常细胞学变化的生物标志物。
方法：该研究涉及2021年11月至2022年8月在开罗大学医院妇产科门诊就诊的74名女性。宫颈样本进行巴氏试验，用格里斯方法评估NOx水平，并通过实时聚合酶链反应检测hrHPVDNA。
结果：在37.8%的女性中检测到高危型HPV。在17.1%的病例中发现了EA，hrHPV阳性病例中的百分比高于阴性病例(35.7%vs.4.3%,p=0.001)。最普遍的hrHPV基因型是HPV16(89.3%)。hrHPV阳性病例的宫颈NOx水平明显较高（37.4µmol/mL，IQR：34.5-45.8）与阴性病例（2.3µmol/mL，IQR：1.2-9.8）（p=<0.001）。高度非典型性患者的NOx水平显着升高（38.0µmol/mL，IQR：24.6-94.7）与NILM和低度非典型病例（5.0µmol/mL，IQR：1.6-33.3和34.5µmol/mL，IQR：分别为11.7-61.7）（p=0.006）。尽管在低级别异型的hrHPV阳性病例中NOx水平（40.4µmol/mL，IQR：33.3-61.8）高于NILM（36.2µmol/mL，IQR：35.7–44.0）和高级非典型性（38.0µmol/mL，IQR：24.6–94.7），差异无统计学意义(p=0.771)。ROC曲线分析表明，>23.61µmol/mL和>11.35µmol/mL的宫颈NOx临界值对预测hrHPV感染和EA具有良好的诊断准确性。分别。
结论：hrHPV感染率高，特别是HPV16，在我们医院需要有针对性的治疗和全面的筛查。宫颈NOx水平升高与hrHPV感染和高度非典型性相关，提示它们可能用作预测hrHPV存在和异常细胞学变化的生物标志物。
