Abnormal cervical cytology is associated with increased nitric oxide release in the uterine cervix

Objective. The human uterine cervix is capable of producing nitric oxide (NO). We studied the impact of cytological changes on the release of cervical NO. Design. Population-based case-control study. Setting. City of Helsinki, Finland. Population. Cervical cytology tests and cervical fluid samples were collected in 297 women. Methods. Cervical cytology tests, classified according to Bethesda criteria, were specifically analyzed for changes typically seen in human papillomavirus (HPV) infection, and the level of NO metabolites (NOx) in cervical fluid was assessed by Griess reaction. Main outcome measures. The difference in cervical fluid NOx between normal and abnormal cytology. Results. Cervical cytology was normal in 219 women and abnormal in 78 women. Among women with abnormal cytology there was both a higher detection rate (89% vs. 71%) and a higher concentration of NOx (median 22.5 mol/l, 95% CI 14.6-31.9 vs. 11.0 mol/l, 95% CI 8.0-16.7) compared to women with normal cytology. Age, parity, use of oral contraceptives, phase of the menstrual cycle, or history of miscarriage or termination of early pregnancy were not linked to an increased cervical NOx level. Conclusions. Cervical cell changes (suggestive of HPV infection) are accompanied by an increased release of NO in the human cervix. The significance of this finding remains uncertain, but in theory, increased release of NO could modify the outcome of cervical infection.