Role of the vaginal microbiological ecosystem and cytokine profile in the promotion of cervical dysplasia: a case-control study.

OBJECTIVE To identify alterations in the cytokine profile and microbial ecosystem of the vagina in association with cervical dysplasia. METHODS Demographics, lifestyle variables and Papanicolau (Pap) smear results of subjects presenting to the same site for gynecologic complaints, obstetric visits or colposcopy were prospectively recorded. Vaginal smear for Gram stain, aerobic and anaerobic culture, pH, and wet mount and KOH examination for Trichomonas vaginalis, Gardnerella vaginalis and yeast organisms were performed. Vaginal lavage specimens were centrifuged, and the pellets and supernatants were assayed for human papillomavirus (HPV) by polymerase chain reaction and for cytokines interleukin (IL)-1beta IL-6, IL-10 and IL-12 by enzyme-linked immunosorbent assay (ELISA) respectively. Subjects with abnormal Pap smears underwent colposcopy and biopsy as indicated. RESULTS Of 51 patients, 32 were referred for colposcopy, 12 presented with gynecologic needs, and seven presented for obstetric visits. Median age was 24 years. Demographics did not differ significantly between the dysplasia and control groups except for a trend towards more sexual partners in the dysplasia group. Biopsies were performed in 81% (26/32) of patients presenting for colposcopy and 17 revealed cervical intraepithelial neoplasia. IL-1beta, IL-6, IL-10, and IL-12 levels were elevated in 63% (20/32), 38% (15/39), 4% (2/49), and 0% of samples respectively. Elevated vaginal lavage IL-1beta was associated with a 6.1 odds ratio (95% confidence interval 1.06-35) of cervical dysplasia. Alterations in other variables studied were not associated with cervical dysplasia. CONCLUSIONS Elevated IL-1beta, possibly representing a complex host inflammatory response to multiple pathogens, was demonstrated in patients with cervical dysplasia.