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Viral and bacterial aetiologies of epithelial ovarian cancer

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Abstract

We sought to analyse the presence of human papillomavirus (HPV), Chlamydia trachomatis and cytomegalovirus (CMV) infection in women with epithelial ovarian carcinomas. Polymerase chain reaction (PCR)-based detection of microbial infections was carried out. A total of 39 tissue samples were analysed with consensus and type-specific primers for HPV, primers specific for the cryptic plasmid of Chlamydia and primers for glycoprotein B of CMV. The samples analysed showed 40%, 80% and 50% positivity for HPV, Chlamydia and CMV infection, respectively, in cancerous ovarian tissues. The HPV type detected was HPV 6, with its genome integrated to the host genome in case of both invasive and borderline tumours and existed episomally in healthy controls. The patients with Chlamydia (odds ratio [OR] 32; 95% confidence interval [CI] 3.33, 307.65) and CMV infection (OR 8; 95% CI 0.888, 72.10) are at significantly higher risk of development of ovarian tumours. The present study validates the theory of chronic infections and inflammation in the pathogenesis of epithelial ovarian cancer. Further seroepidemiological studies and large fresh tissue sampling may represent the real prevalence of infections among ovarian carcinoma patients. This study is the first of its kind in detecting the bacterial and viral aetiologies in the development of ovarian carcinoma among Indian women.

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References

  1. Posadas EM, Davidson B, Kohn EC (2004) Proteomics and ovarian cancer: implications for diagnosis and treatment: a critical review of the recent literature. Curr Opin Oncol 16:478–484

    Article  PubMed  CAS  Google Scholar 

  2. Berchuck A, Heron KA, Carney ME, Lancaster JM, Fraser EG, Vinson VL, Deffenbaugh AM, Miron A, Marks JR, Futreal PA, Frank TS (1998) Frequency of germline and somatic BRCA1 mutations in ovarian cancer. Clin Cancer Res 4:2433–2437

    PubMed  CAS  Google Scholar 

  3. Idahl A, Lundin E, Jurstrand M, Kumlin U, Elgh F, Ohlson N, Ottander U (2011) Chlamydia trachomatis and Mycoplasma genitalium plasma antibodies in relation to epithelial ovarian tumors. Infect Dis Obstet Gynecol 2011:824627. doi:10.1155/2011/824627

  4. Moss SF, Blaser MJ (2005) Mechanisms of disease: inflammation and the origins of cancer. Nat Clin Pract Oncol 2:90–97

    Article  PubMed  CAS  Google Scholar 

  5. Koskela P, Anttila T, Bjørge T, Brunsvig A, Dillner J, Hakama M, Hakulinen T, Jellum E, Lehtinen M, Lenner P, Luostarinen T, Pukkala E, Saikku P, Thoresen S, Youngman L, Paavonen J (2000) Chlamydia trachomatis infection as a risk factor for invasive cervical cancer. Int J Cancer 85:35–39

    Article  PubMed  CAS  Google Scholar 

  6. Madeleine MM, Anttila T, Schwartz SM, Saikku P, Leinonen M, Carter JJ, Wurscher M, Johnson LG, Galloway DA, Daling JR (2007) Risk of cervical cancer associated with Chlamydia trachomatis antibodies by histology, HPV type and HPV cofactors. Int J Cancer 120:650–655

    Article  PubMed  CAS  Google Scholar 

  7. Risch HA, Howe GR (1995) Pelvic inflammatory disease and the risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 4:447–451

    PubMed  CAS  Google Scholar 

  8. Boom R, Sol CJA, Salimans MMM, Jansen CL, Wertheim-van Dillen PM, van der Noordaa J (1990) Rapid and simple method for purification of nucleic acids. J Clin Microbiol 28:495–503

    PubMed  CAS  Google Scholar 

  9. Høgdall EVS, Kjaer SK, Blaakaer J, Christensen L, Glud E, Vuust J, Høgdall CK (2006) P53 mutations in tissue from Danish ovarian cancer patients: from the Danish “MALOVA” ovarian cancer study. Gynecol Oncol 100:76–82

    Article  PubMed  Google Scholar 

  10. Bauer HM, Greer CE, Manos MM (1992) Determination of genital HPV infection using consensus PCR. In: Herrington CS, McGee JOD (eds) Diagnostic molecular pathology: a practical approach. Oxford University Press, Oxford, pp 131–152

    Google Scholar 

  11. Bauer HM, Hildesheim A, Schiffman MH, Glass AG, Rush BB, Scott DR, Cadell DM, Kurman RJ, Manos MM (1993) Determinants of genital human papillomavirus infection in low-risk women in Portland, Oregon. Sex Trans Dis 20:274–278

    Article  CAS  Google Scholar 

  12. de Roda Husman AM, Walboomers JM, van den Brule AJ, Meijer CJ, Snijders PJ (1995) The use of general primers GP5 and GP6 elongated at their 3’ ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol 76:1057–1062

    Article  PubMed  Google Scholar 

  13. Mahony JB, Luinstra KE, Jang D, Sellors J, Chernesky MA (1992) Chlamydia trachomatis confirmatory testing of PCR-positive genitourinary specimens using a second set of plasmid primers. Mol Cell Probes 6:381–388

    Article  PubMed  CAS  Google Scholar 

  14. Kuhn DE, Beall CJ, Kolattukudy PE (1995) The cytomegalovirus US28 protein binds multiple CC chemokines with high affinity. Biochem Biophys Res Commun 211:325–330

    Article  PubMed  CAS  Google Scholar 

  15. Gupta J, Pilotti S, Rilke F, Shah K (1987) Association of human papillomavirus type 16 with neoplastic lesions of the vulva and other genital sites by in situ hybridization. Am J Pathol 127:206–215

    PubMed  CAS  Google Scholar 

  16. Shah KV, Howley PM (1996) Papillomaviruses. In: Fields BN, Knipe DM, Howley PM (eds) Fields virology, vol 2. Lippincott-Raven, Philadelphia, pp 2077–2109

    Google Scholar 

  17. Dillner J, Lehtinen M, Björge T, Luostarinen T, Youngman L, Jellum E, Koskela P, Gislefoss RE, Hallmans G, Paavonen J, Sapp M, Schiller JT, Hakulinen T, Thoresen S, Hakama M (1997) Prospective seroepidemiologic study of human papillomavirus infection as a risk factor for invasive cervical cancer. J Natl Cancer Inst 89:1293–1299

    Article  PubMed  CAS  Google Scholar 

  18. Runnebaum IB, Maier S, Tong XW, Rosenthal HE, Möbus VJ, Kieback DG, Kreienberg R (1995) Human papillomavirus integration is not associated with advanced epithelial ovarian cancer in German patients. Cancer Epidemiol Biomarkers Prev 4:573–575

    PubMed  CAS  Google Scholar 

  19. Trottier AM, Provencher D, Mes-Masson AM, Vauclair R, Coutlée F (1995) Absence of human papillomavirus sequences in ovarian pathologies. J Clin Microbiol 33:1011–1013

    PubMed  CAS  Google Scholar 

  20. Wu QJ, Guo M, Lu ZM, Li T, Qiao HZ, Ke Y (2003) Detection of human papillomavirus-16 in ovarian malignancy. Br J Cancer 89:672–675

    Article  PubMed  Google Scholar 

  21. Idahl A, Lundin E, Elgh F, Jurstrand M, Møller JK, Marklund I, Lindgren P, Ottander U (2010) Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, human papillomavirus, and polyomavirus are not detectable in human tissue with epithelial ovarian cancer, borderline tumor, or benign conditions. Am J Obstet Gynecol 202:71.e1–71.e6

    Article  Google Scholar 

  22. Dürst M, Kleinheinz A, Hotz M, Gissmann L (1985) The physical state of human papillomavirus type 16 DNA in benign and malignant genital tumours. J Gen Virol 66:1515–1522

    Article  PubMed  Google Scholar 

  23. Galehouse D, Jenison E, DeLucia A (1992) Differences in the integration pattern and episomal forms of human papillomavirus type 16 DNA found within an invasive cervical neoplasm and its metastasis. Virology 186:339–341

    Article  PubMed  CAS  Google Scholar 

  24. Gissmann L, Wolnik L, Ikenberg H, Koldovsky U, Schnürch HG, zur Hausen H (1983) Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers. Proc Nat Acad Sci USA 80:560–563

    Article  PubMed  CAS  Google Scholar 

  25. Boshart M, zur Hausen H (1986) Human papillomaviruses in Buschke–Löwenstein tumors: physical state of the DNA and identification of a tandem duplication in the noncoding region of a human papillomavirus 6 subtype. J Virol 58:963–966

    PubMed  CAS  Google Scholar 

  26. Rando RF, Sedlacek TV, Hunt J, Jenson AB, Kurman RJ, Lancaster WD (1986) Verrucous carcinoma of the vulva associated with an unusual type 6 human papillomavirus. Obstet Gynecol 67:70S–75S

    Article  PubMed  CAS  Google Scholar 

  27. Byrne JC, Tsao MS, Fraser RS, Howley PM (1987) Human papillomavirus-11 DNA in a patient with chronic laryngotracheobronchial papillomatosis and metastatic squamous-cell carcinoma of the lung. N Engl J Med 317:873–878

    Article  PubMed  CAS  Google Scholar 

  28. Manias DA, Ostrow RS, Mcglennen RC, Estensen RD, Faras AJ (1989) Characterization of integrated human papillomavirus type 11 DNA in primary and metastatic tumors from a renal transplant recipient. Cancer Res 49:2514–2519

    PubMed  CAS  Google Scholar 

  29. Bercovich JA, Centeno CR, Aguilar OG, Grinstein S, Kahn T (1991) Presence and integration of human papillomavirus type 6 in a tonsillar carcinoma. J Gen Virol 72:2569–2572

    Article  PubMed  Google Scholar 

  30. Lee JW, Choi CH, Choi JJ, Park YA, Kim SJ, Hwang SY, Kim WY, Kim TJ, Lee JH, Kim BG, Bae DS (2008) Altered microRNA expression in cervical carcinomas. Clin Cancer Res 14:2535–2542

    Article  PubMed  CAS  Google Scholar 

  31. Mitao M, Reumann W, Winkler B, Richart RM, Fujiwara A, Crum CP (1984) Chlamydial cervicitis and cervical intraepithelial neoplasia: an immunohistochemical analysis. Gynecol Oncol 19:90–97

    Article  PubMed  CAS  Google Scholar 

  32. Kiviat NB, Paavonen JA, Brockway J, Critchlow CW, Brunham RC, Stevens CE, Stamm WE, Kuo CC, DeRouen T, Holmes KK (1985) Cytologic manifestations of cervical and vaginal infections. I. Epithelial and inflammatory cellular changes. JAMA 253:989–996

    Article  PubMed  CAS  Google Scholar 

  33. Fan T, Lu H, Hu H, Shi L, McClarty GA, Nance DM, Greenberg AH, Zhong G (1998) Inhibition of apoptosis in Chlamydia-infected cells: blockade of mitochondrial cytochrome C release and caspase activation. J Exp Med 187:487–496

    Article  PubMed  CAS  Google Scholar 

  34. Felley-Bosco E (1998) Role of nitric oxide in genotoxicity: implication for carcinogenesis. Cancer Metastasis Rev 17:25–37

    Article  PubMed  CAS  Google Scholar 

  35. Castle PE, Hillier SL, Rabe LK, Hildesheim A, Herrero R, Bratti MC, Sherman ME, Burk RD, Rodriguez AC, Alfaro M, Hutchinson ML, Morales J, Schiffman M (2001) An association of cervical inflammation with high-grade cervical neoplasia in women infected with oncogenic human papillomavirus (HPV). Cancer Epidemiol Biomarkers Prev 10:1021–1027

    PubMed  CAS  Google Scholar 

  36. Prozialeck WC, Fay MJ, Lamar PC, Pearson CA, Sigar I, Ramsey KH (2002) Chlamydia trachomatis disrupts N-cadherin-dependent cell–cell junctions and sequesters beta-catenin in human cervical epithelial cells. Infect Immun 70:2605–2613

    Article  PubMed  CAS  Google Scholar 

  37. Sharma TM, Nadasdy T, Leech RW, Kingma DW, Johnson LD, Hanson-Painton O (1994) In situ DNA hybridization study of ‘primary’ cytomegalovirus (CMV) oophoritis. Acta Obstet Gynecol Scand 73:429–431

    Article  PubMed  CAS  Google Scholar 

  38. Manfredi R, Alampi G, Talò S, Calza L, Tadolini M, Martinelli GN, Chiodo F (2000) Silent oophoritis due to cytomegalovirus in a patient with advanced HIV disease. Int J STD AIDS 11:410–412

    Article  PubMed  CAS  Google Scholar 

  39. Yu J, Solano FX Jr, Seethala RR (2007) Bilateral cytomegalovirus (CMV) oophoritis mimicking widely metastatic carcinoma: a case report and review of the literature. Diagn Pathol 2:50

    Article  PubMed  Google Scholar 

  40. Hendrix RM, Wagenaar M, Slobbe RL, Bruggeman CA (1997) Widespread presence of cytomegalovirus DNA in tissues of healthy trauma victims. J Clin Pathol 50:59–63

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

K.N. is thankful to the Indian Council of Medical Research (ICMR; 5/13/88/06/NCD-III) for providing financial support to carry out the research work. S.S. is thankful to the ICMR for providing the Senior Research Fellowship (3/2/2/63/2011/NCD-III). The authors greatly acknowledge the Vice-Chancellor of Bharathidasan University and Dr. V.J. Senthil, the Director of GVN Hospital, Tiruchirappalli, Tamilnadu, India.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamilnadu, India

    S. Shanmughapriya & N. Vasanthi

  2. Department of Surgical Oncology, Dr. G. Vishwanathan Hospital, Tiruchirappalli, Tamilnadu, India

    G. SenthilKumar

  3. Medical Microbiology Laboratory, Department of Microbiology, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamilnadu, 620 024, India

    S. Shanmughapriya, K. Vinodhini & K. Natarajaseenivasan

  4. Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India

    B. C. Das

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  1. S. Shanmughapriya
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  3. K. Vinodhini
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Correspondence to K. Natarajaseenivasan.

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Authors’ Contribution

S.S., K.N. and B.C.D. designed the study and drafted the manuscript, S.S. carried out the experiments, G.S.K. performed the surgery and carried out the histopathological findings, K.N. and V.N. revised the manuscript critically, and K.V. provided the positive control cervical tissue DNA.

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Shanmughapriya, S., SenthilKumar, G., Vinodhini, K. et al. Viral and bacterial aetiologies of epithelial ovarian cancer. Eur J Clin Microbiol Infect Dis 31, 2311–2317 (2012). https://doi.org/10.1007/s10096-012-1570-5

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  • DOI: https://doi.org/10.1007/s10096-012-1570-5

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