Cervical nitric oxide release and persistence of high-risk human papillomavirus in women

Abstract

Nitric oxide may serve as one cofactor for human papillomavirus (HPV)-induced development of cervical cancer. Therefore, we first assessed the levels of cervical fluid nitric oxide metabolite (NOx) in 283 women with and without high-risk (hr) HPV. The NOx level in women with hr HPV (48.4 μmol/L [95% CI: 39.4-56.6], n = 199) was higher (p < 0.001) than that in women without hr HPV (24.6 μmol/L [95% CI: 19.1-38.7], n = 84). Second, we evaluated if cervical fluid NOx levels could predict the persistence of hr HPV. Therefore, we followed up 113 women with detectable hr HPV without any treatment for 12 mo and repeated hr HPV test. High-risk HPV persisted in 72 women (64%) and disappeared in 41 women (36%). The median basal levels of NOx were higher (p = 0.02) in women with persistent hr HPV (56.9 μmol/L [95% CI: 48.7-81.0]) compared to those with eradicated hr HPV (37.7 μmol/L [95% CI: 27.0-58.0]). The NOx level higher than the 75th percentile (>87.0 μmol/L) predicted hr HPV persistence (OR = 4.1 [95% CI: 1.3-13.1]). This cutoff level of NOx showed 33% sensitivity and 90% specificity in predicting the persistence of hr HPV, but it failed to predict cytological progression or regression in 12 mo. In conclusion, high cervical fluid NOx appears to be connected to the persistence of hr HPV, but the low predictive capacity of NOx prevents its clinical use at this phase.