Role of the Vaginal Microbiological Ecosystem and Cytokine Profile in the Promotion of Cervical Dysplasia: A Case–Control Study

Abstract

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 forTrichomonas vaginalis,Gardnerella vaginalisand 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)-1ß 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-1ß, 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-1ß 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-1ß, possibly representing a complex host inflammatory response to multiple pathogens, was demonstrated in patients with cervical dysplasia.