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Infectious Diseases in Obstetrics and Gynecology logoLink to Infectious Diseases in Obstetrics and Gynecology
. 2002;10(4):181–186. doi: 10.1155/S1064744902000200

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

Kian Behbakht 1, Jennifer Friedman 1, Ira Heimler 1, Alla Aroutcheva 1, Jose Simoes 1, Sebastian Faro 1
PMCID: PMC1784618  PMID: 12648311

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 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.

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Selected References

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  1. Amsel R., Totten P. A., Spiegel C. A., Chen K. C., Eschenbach D., Holmes K. K. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med. 1983 Jan;74(1):14–22. doi: 10.1016/0002-9343(83)91112-9. [DOI] [PubMed] [Google Scholar]
  2. Aroutcheva A. A., Simoes J. A., Behbakht K., Faro S. Gardnerella vaginalis isolated from patients with bacterial vaginosis and from patients with healthy vaginal ecosystems. Clin Infect Dis. 2001 Sep 5;33(7):1022–1027. doi: 10.1086/323030. [DOI] [PubMed] [Google Scholar]
  3. Bedell M. A., Jones K. H., Laimins L. A. The E6-E7 region of human papillomavirus type 18 is sufficient for transformation of NIH 3T3 and rat-1 cells. J Virol. 1987 Nov;61(11):3635–3640. doi: 10.1128/jvi.61.11.3635-3640.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clerici M., Merola M., Ferrario E., Trabattoni D., Villa M. L., Stefanon B., Venzon D. J., Shearer G. M., De Palo G., Clerici E. Cytokine production patterns in cervical intraepithelial neoplasia: association with human papillomavirus infection. J Natl Cancer Inst. 1997 Feb 5;89(3):245–250. doi: 10.1093/jnci/89.3.245. [DOI] [PubMed] [Google Scholar]
  5. Guijon F., Paraskevas M., Rand F., Heywood E., Brunham R., McNicol P. Vaginal microbial flora as a cofactor in the pathogenesis of uterine cervical intraepithelial neoplasia. Int J Gynaecol Obstet. 1992 Mar;37(3):185–191. doi: 10.1016/0020-7292(92)90379-w. [DOI] [PubMed] [Google Scholar]
  6. Kurman R. J., Henson D. E., Herbst A. L., Noller K. L., Schiffman M. H. Interim guidelines for management of abnormal cervical cytology. The 1992 National Cancer Institute Workshop. JAMA. 1994 Jun 15;271(23):1866–1869. [PubMed] [Google Scholar]
  7. Majeed G. S., Glew S., Bidwell J. An association between LSIL and the high secretor phenotype of IL-1beta. Gynecol Oncol. 1999 Jun;73(3):359–361. doi: 10.1006/gyno.1999.5366. [DOI] [PubMed] [Google Scholar]
  8. Mattsby-Baltzer I., Platz-Christensen J. J., Hosseini N., Rosén P. IL-1beta, IL-6, TNFalpha, fetal fibronectin, and endotoxin in the lower genital tract of pregnant women with bacterial vaginosis. Acta Obstet Gynecol Scand. 1998 Aug;77(7):701–706. [PubMed] [Google Scholar]
  9. Mota F., Calder V., Rutault K., Singer A., Chain B. Characterization of soluble factors from cultures of premalignant cervical epithelium. Eur J Gynaecol Oncol. 1999;20(4):262–267. [PubMed] [Google Scholar]
  10. Mota F., Rayment N., Chong S., Singer A., Chain B. The antigen-presenting environment in normal and human papillomavirus (HPV)-related premalignant cervical epithelium. Clin Exp Immunol. 1999 Apr;116(1):33–40. doi: 10.1046/j.1365-2249.1999.00826.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Nugent R. P., Krohn M. A., Hillier S. L. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol. 1991 Feb;29(2):297–301. doi: 10.1128/jcm.29.2.297-301.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pavić N. Is there a local production of nitrosamines by the vaginal microflora in anaerobic vaginosis/trichomoniasis? Med Hypotheses. 1984 Dec;15(4):433–436. doi: 10.1016/0306-9877(84)90159-2. [DOI] [PubMed] [Google Scholar]
  13. Platz-Christensen J. J., Sundström E., Larsson P. G. Bacterial vaginosis and cervical intraepithelial neoplasia. Acta Obstet Gynecol Scand. 1994 Aug;73(7):586–588. doi: 10.3109/00016349409006278. [DOI] [PubMed] [Google Scholar]
  14. Sha B. E., D'Amico R. D., Landay A. L., Spear G. T., Massad L. S., Rydman R. J., Warner N. A., Padnick J., Ackatz L., Charles L. A. Evaluation of immunologic markers in cervicovaginal fluid of HIV-infected and uninfected women: implications for the immunologic response to HIV in the female genital tract. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Nov 1;16(3):161–168. doi: 10.1097/00042560-199711010-00004. [DOI] [PubMed] [Google Scholar]
  15. Sjöberg I., Håkansson S. Endotoxin in vaginal fluid of women with bacterial vaginosis. Obstet Gynecol. 1991 Feb;77(2):265–266. doi: 10.1097/00006250-199102000-00020. [DOI] [PubMed] [Google Scholar]
  16. Sonnex C. The amine test: a simple, rapid, inexpensive method for diagnosing bacterial vaginosis. Br J Obstet Gynaecol. 1995 Feb;102(2):160–161. doi: 10.1111/j.1471-0528.1995.tb09071.x. [DOI] [PubMed] [Google Scholar]
  17. Sturm-Ramirez K., Gaye-Diallo A., Eisen G., Mboup S., Kanki P. J. High levels of tumor necrosis factor-alpha and interleukin-1beta in bacterial vaginosis may increase susceptibility to human immunodeficiency virus. J Infect Dis. 2000 Jul 18;182(2):467–473. doi: 10.1086/315713. [DOI] [PubMed] [Google Scholar]
  18. Tjiong M. Y., van der Vange N., ten Kate F. J., Tjong-A-Hung S. P., ter Schegget J., Burger M. P., Out T. A. Increased IL-6 and IL-8 levels in cervicovaginal secretions of patients with cervical cancer. Gynecol Oncol. 1999 May;73(2):285–291. doi: 10.1006/gyno.1999.5358. [DOI] [PubMed] [Google Scholar]
  19. Wingo P. A., Tong T., Bolden S. Cancer statistics, 1995. CA Cancer J Clin. 1995 Jan-Feb;45(1):8–30. doi: 10.3322/canjclin.45.1.8. [DOI] [PubMed] [Google Scholar]

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