Ovarian microbiota and Ovarian cancer: an overview and update meta-analysis

This is a preview and has not been published.

Ovarian microbiota and Ovarian cancer: an overview and update meta-analysis

Authors

  • Mariano Catello Di Donna Unit of Gynegologic Oncology, National Institute of Tumors IRCCS Fondazione G. Pascale, Napoli, Italy
  • Giuseppe Cucinella Unit of Gynegologic Oncology, National Institute of Tumors IRCCS Fondazione G. Pascale, Napoli, Italy
  • Maria Cristina Solazzo Azienda Ospedaliera Universitaria Università degli Studi della Campania Luigi Vanvitelli: Naples, IT
  • Vito Andrea Capozzi Department of Gynecology and Obstetrics of Parma, 43125, Parma, Italy.
  • Isabella Rotondella Department of Gynecology and Obstetrics of Parma, 43125, Parma, Italy.
  • Andrea Etrusco Unit of Obstetrics and Gynecology, “Paolo Giaccone” Hospital, Palermo, Italy.
  • Antonio Simone Laganà Unit of Obstetrics and Gynecology, “Paolo Giaccone” Hospital, Palermo, Italy.
  • Elisa Scarpelli Department of Gynecology and Obstetrics of Parma, 43125, Parma, Italy.
  • Paola Romeo Obstetrics and Gynecology Unit, Department of Human Pathology of Adult and Childhood "G. Barresi", University of Messina, 98125 Messina, Italy
  • Vittorio Palmara Obstetrics and Gynecology Unit, Department of Human Pathology of Adult and Childhood "G. Barresi", University of Messina, 98125 Messina, Italy.
  • Vito Chiantera Unit of Gynegologic Oncology, National Institute of Tumors IRCCS Fondazione G. Pascale, Napoli, Italy
  • Stefano Cianci Obstetrics and Gynecology Unit, Department of Human Pathology of Adult and Childhood "G. Barresi", University of Messina, 98125 Messina, Italy.
  • Roberto Berretta Department of Gynecology and Obstetrics of Parma, 43125, Parma, Italy

Keywords:

Ovarian Cancer , Ovarian Microbiota, Dysbiosis

Abstract

Background: Ovarian cancer (OC) remains the most lethal gynecological malignancy, although  advancements in treatment strategies. Emerging data suggested the potential role of ovarian microbiota in ovarian cancer pathogenesis. The objective of this review and meta-analysis is to analyze available literature to investigate this correlation.

Methods: According to the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, the Pubmed database and the Embase database were searched in February 2024. No limitation of the countries was considered.

Results: Twenty-seven studies met the inclusion criteria. Five thousand and fourteen ovarian carcinoma cases were included of which 1659 (33.1%) showed dysbiosis. The fixed-effect model and the random-effect model showed no significant correlation between ovarian cancer patients and dysbiosis (p<0.001 and p<0.001 with 95% Confidence Interval 0.21-0.35 and effect size 0.28, respectively). The heterogeneity between studies was high with an I2 of 95.76% (p<0.001).

Conclusions: Our meta-analysis suggests no significant difference in  dysbiosis prevalence between OC patients and controls. Considering the substantial heterogeneity found, more studies with control groups and precise methodologies are needed to further evaluate the potential role of the ovarian microbiota in the OC.

References

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5-29. doi:10.3322/caac.21254

Torre LA, Islami F, Siegel RL, Ward EM, Jemal A. Global Cancer in Women: Burden and Trends. Cancer Epidemiology, Biomarkers & Prevention. 2017;26(4):444-457. doi:10.1158/1055-9965.EPI-16-0858

Di Donna MC, Cucinella G, Zaccaria G, et al. Concordance of Radiological, Laparoscopic and Laparotomic Scoring to Predict Complete Cytoreduction in Women with Advanced Ovarian Cancer. Cancers (Basel). 2023;15(2):500. doi:10.3390/cancers15020500

Janavičius R. Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control. EPMA Journal. 2010;1(3):397-412. doi:10.1007/s13167-010-0037-y

Carlson JW, Miron A, Jarboe EA, et al. Serous Tubal Intraepithelial Carcinoma: Its Potential Role in Primary Peritoneal Serous Carcinoma and Serous Cancer Prevention. Journal of Clinical Oncology. 2008;26(25):4160-4165. doi:10.1200/JCO.2008.16.4814

Chambers LM, Bussies P, Vargas R, et al. The Microbiome and Gynecologic Cancer: Current Evidence and Future Opportunities. Curr Oncol Rep. 2021;23(8):92. doi:10.1007/s11912-021-01079-x

Cazzaniga M, Cardinali M, Di Pierro F, Bertuccioli A. Ovarian Microbiota, Ovarian Cancer and the Underestimated Role of HPV. Int J Mol Sci. 2022;23(24). doi:10.3390/ijms232416019

PRICE MJ, ADES AE, WELTON NJ, SIMMS I, HORNER PJ. Pelvic inflammatory disease and salpingitis: incidence of primary and repeat episodes in England. Epidemiol Infect. 2017;145(1):208-215. doi:10.1017/S0950268816002065

Zhou Z, Zeng F, Yuan J, et al. Pelvic inflammatory disease and the risk of ovarian cancer: a meta-analysis. Cancer Causes & Control. 2017;28(5):415-428. doi:10.1007/s10552-017-0873-3

Fortner RT, Terry KL, Bender N, et al. Sexually transmitted infections and risk of epithelial ovarian cancer: results from the Nurses’ Health Studies. Br J Cancer. 2019;120(8):855-860. doi:10.1038/s41416-019-0422-9

Ingerslev K, Høgdall E, Skovrider-Ruminski W, et al. The prevalence of EBV and CMV DNA in epithelial ovarian cancer. Infect Agent Cancer. 2019;14(1). doi:10.1186/s13027-019-0223-z

zur Hausen H. Papillomaviruses in the causation of human cancers — a brief historical account. Virology. 2009;384(2):260-265. doi:10.1016/j.virol.2008.11.046

Wai KC, Strohl MP, van Zante A, Ha PK. Molecular Diagnostics in Human Papillomavirus-Related Head and Neck Squamous Cell Carcinoma. Cells. 2020;9(2):500. doi:10.3390/cells9020500

Cherif S, Amine A, Thies S, et al. Prevalence of human papillomavirus detection in ovarian cancer: a meta-analysis. European Journal of Clinical Microbiology & Infectious Diseases. 2021;40(9):1791-1802. doi:10.1007/s10096-021-04282-7

Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009;6(7). doi:10.1371/journal.pmed.1000097

Skarga E, Surcel HM, Kaaks R, Waterboer T, Fortner RT. Sexually Transmitted Infections and Risk of Epithelial Ovarian Cancer: Results From the Finnish Maternity Cohort. J Infect Dis. 2023;228(11):1621-1629. doi:10.1093/infdis/jiad171

Jonsson S, Lundin E, Elgh F, Ottander U, Idahl A. Chlamydia trachomatis and Anti-MUC1 Serology and Subsequent Risk of High-Grade Serous Ovarian Cancer: A Population-Based Case–Control Study in Northern Sweden. Transl Oncol. 2020;13(1):86-91. doi:10.1016/j.tranon.2019.09.007

Ness RB, Shen C, Bass D, et al. Chlamydia trachomatis serology in women with and without ovarian cancer. Infect Dis Obstet Gynecol. 2008;2008. doi:10.1155/2008/219672

Laban M, Ibrahim EA, Hassanin AS, et al. Chlamydia trachomatis infection in primary fallopian tube and high-grade serous ovarian cancers: A pilot study. Int J Womens Health. 2019;11:199-205. doi:10.2147/IJWH.S188938

Holster T, Urpilainen E, Paavonen J, Puistola U, Puolakkainen M. Immunological Markers of Chlamydia trachomatis Infection in Epithelial Ovarian Cancer. Anticancer Res. 2023;43(9):4037-4043. doi:10.21873/anticanres.16592

Idahl A, Le Cornet C, González Maldonado S, et al. Serologic markers of Chlamydia trachomatis and other sexually transmitted infections and subsequent ovarian cancer risk: Results from the EPIC cohort. Int J Cancer. 2020;147(8):2042-2052. doi:10.1002/ijc.32999

Yang H, Zhang J zhi, Shou C chao. Detection of mycoplasma hyorhinis infection in ovarian cancer with in situ hybridization and immunohistochemistry. Clinical Oncology and Cancer Research. 2010;7(5):294-298. doi:10.1007/s11805-010-0534-8

Bilyk OO, Pande NT, Pejovic T, Buchynska LG. THE FREQUENCY OF HUMAN PAPILLOMA VIRUS TYPES 16, 18 IN UPPER GENITAL TRACT OF WOMEN AT HIGH RISK OF DEVELOPING OVARIAN CANCER. Vol 36.; 2014.

Dadashi M, Eslami G, Faghihloo E, et al. Detection of human papilloma virus type 16 in epithelial ovarian tumors samples. Arch Clin Infect Dis. 2017;12(1). doi:10.5812/archcid.39666

Ingerslev K, Hogdall E, Skovrider-Ruminski W, et al. High-risk HPV is not associated with epithelial ovarian cancer in a Caucasian population. Infect Agent Cancer. 2016;11(1):39. doi:10.1186/s13027-016-0087-4

Kuscu E, Ozdemir BH, Erkanli S, Haberal A. HPV and p53 expression in epithelial ovarian carcinoma. Eur J Gynaecol Oncol. 2005;26(6):642-645.

Roos P, Orlando PA, Fagerstrom RM, Pepper JW. In North America, some ovarian cancers express the oncogenes of preventable human papillomavirus HPV-18. Sci Rep. 2015;5. doi:10.1038/srep08645

Shokouh MR, Safaei A, Moattari A, Sarvari J. Association of human papilloma virus and epstein-barr virus with ovarian cancer in shiraz, southwestern Iran. Iran J Pathol. 2020;15(4):292-298. doi:10.30699/ijp.2020.119681.2306

Wu QJ, Guo M, Lu ZM, Li T, Qiao HZ, Ke Y. Detection of human papillomavirus-16 in ovarian malignancy. Br J Cancer. 2003;89(4):672-675. doi:10.1038/sj.bjc.6601172

Atalay F, Taskiran C, Taner MZ, Pak I, Or M, Tuncer S. Detection of human papillomavirus DNA and genotyping in patients with epithelial ovarian carcinoma. Journal of Obstetrics and Gynaecology Research. 2007;33(6):823-828. doi:10.1111/j.1447-0756.2007.00663.x

Hassan ZK, Hafez MM, Kamel MM, Zekri ARN. Human papillomavirus genotypes and methylation of CADM1, PAX1, MAL and ADCYAP1 genes in epithelial ovarian cancer patients. Asian Pacific Journal of Cancer Prevention. 2017;18(1):169-176. doi:10.22034/APJCP.2017.18.1.169

Zhang PP, Zhou L, Cao JS, et al. Possible Epithelial Ovarian Cancer Association with HPV18 or HPV33 Infection. Asian Pac J Cancer Prev. 2016;17(6):2959-2964.

Penny SM. Ovarian Cancer: An Overview. Radiol Technol. 2020;91(6):561-575.

Polk DB, Peek RM. Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer. 2010;10(6):403-414. doi:10.1038/nrc2857

Quaglio AEV, Grillo TG, Oliveira ECS De, Stasi LC Di, Sassaki LY. Gut microbiota, inflammatory bowel disease and colorectal cancer. World J Gastroenterol. 2022;28(30):4053-4060. doi:10.3748/wjg.v28.i30.4053

Hu X, Xu X, Zeng X, et al. Gut microbiota dysbiosis promotes the development of epithelial ovarian cancer via regulating Hedgehog signaling pathway. Gut Microbes. 2023;15(1). doi:10.1080/19490976.2023.2221093

Fulbright LE, Ellermann M, Arthur JC. The microbiome and the hallmarks of cancer. PLoS Pathog. 2017;13(9):e1006480. doi:10.1371/journal.ppat.1006480

Comen EA, Bowman RL, Kleppe M. Underlying Causes and Therapeutic Targeting of the Inflammatory Tumor Microenvironment. Front Cell Dev Biol. 2018;6. doi:10.3389/fcell.2018.00056

Mahoney DE, Chalise P, Rahman F, Pierce JD. Influences of Gastrointestinal Microbiota Dysbiosis on Serum Proinflammatory Markers in Epithelial Ovarian Cancer Development and Progression. Cancers (Basel). 2022;14(12):3022. doi:10.3390/cancers14123022

Ravel J, Gajer P, Abdo Z, et al. Vaginal microbiome of reproductive-age women. Proceedings of the National Academy of Sciences. 2011;108(supplement_1):4680-4687. doi:10.1073/pnas.1002611107

Champer M, Wong A, Champer J, et al. The role of the vaginal microbiome in gynaecological cancer. BJOG. 2018;125(3):309-315. doi:10.1111/1471-0528.14631

Brotman RM, Shardell MD, Gajer P, et al. Interplay Between the Temporal Dynamics of the Vaginal Microbiota and Human Papillomavirus Detection. Journal of Infectious Diseases. 2014;210(11):1723-1733. doi:10.1093/infdis/jiu330

Gao W, Weng J, Gao Y, Chen X. Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection: a cross-sectional study. BMC Infect Dis. 2013;13(1):271. doi:10.1186/1471-2334-13-271

Walther-António MRS, Chen J, Multinu F, et al. Potential contribution of the uterine microbiome in the development of endometrial cancer. Genome Med. 2016;8(1):122. doi:10.1186/s13073-016-0368-y

Li C, Feng Y, Yang C, et al. Association between vaginal microbiota and the progression of ovarian cancer. J Med Virol. 2023;95(7). doi:10.1002/jmv.28898

Nené NR, Reisel D, Leimbach A, et al. Association between the cervicovaginal microbiome, BRCA1 mutation status, and risk of ovarian cancer: a case-control study. Lancet Oncol. 2019;20(8):1171-1182. doi:10.1016/S1470-2045(19)30340-7

Łaniewski P, Ilhan ZE, Herbst-Kralovetz MM. The microbiome and gynaecological cancer development, prevention and therapy. Nat Rev Urol. 2020;17(4):232-250. doi:10.1038/s41585-020-0286-z

Jennings LK, Krywko DM. Pelvic Inflammatory Disease.; 2024.

Chumduri C, Gurumurthy RK, Zadora PK, Mi Y, Meyer TF. Chlamydia Infection Promotes Host DNA Damage and Proliferation but Impairs the DNA Damage Response. Cell Host Microbe. 2013;13(6):746-758. doi:10.1016/j.chom.2013.05.010

Chan PJ, Seraj IM, Kalugdan TH, King A. Prevalence of Mycoplasma Conserved DNA in Malignant Ovarian Cancer Detected Using Sensitive PCR–ELISA. Gynecol Oncol. 1996;63(2):258-260. doi:10.1006/gyno.1996.0316

Shanmughapriya S, SenthilKumar G, Vinodhini K, Das BC, Vasanthi N, Natarajaseenivasan K. Viral and bacterial aetiologies of epithelial ovarian cancer. European Journal of Clinical Microbiology & Infectious Diseases. 2012;31(9):2311-2317. doi:10.1007/s10096-012-1570-5

Kurman RJ, Shih IM. The Origin and Pathogenesis of Epithelial Ovarian Cancer: A Proposed Unifying Theory. American Journal of Surgical Pathology. 2010;34(3):433-443. doi:10.1097/PAS.0b013e3181cf3d79

Paavonen J, Turzanski Fortner R, Lehtinen M, Idahl A. Chlamydia trachomatis , Pelvic Inflammatory Disease, and Epithelial Ovarian Cancer. J Infect Dis. 2021;224(Supplement_2):S121-S127. doi:10.1093/infdis/jiab017

Capozzi VA, Incognito GG, Scarpelli E, et al. Exploring the Relationship between Ovarian Cancer and Genital Microbiota: A Systematic Review and Meta-Analysis. J Pers Med. 2024;14(4):351. doi:10.3390/jpm14040351

Casson N, Entenza JM, Greub G. Serological Cross-Reactivity between Different Chlamydia -Like Organisms. J Clin Microbiol. 2007;45(1):234-236. doi:10.1128/JCM.01867-06

Nour NM. Cervical cancer: a preventable death. Rev Obstet Gynecol. 2009;2(4):240-244.

Kaufman RH, Bornstein J, Gordon AN, Adam E, Kaplan AL, Adler-Storthz K. Detection of human papillomavirus DNA in advanced epithelial ovarian carcinoma. Gynecol Oncol. 1987;27(3):340-349. doi:10.1016/0090-8258(87)90256-3

Svahn MF, Faber MT, Christensen J, Norrild B, Kjaer SK. Prevalence of human papillomavirus in epithelial ovarian cancer tissue. A meta‐analysis of observational studies. Acta Obstet Gynecol Scand. 2014;93(1):6-19. doi:10.1111/aogs.12254

Chen Y, Williams V, Filippova M, Filippov V, Duerksen-Hughes P. Viral Carcinogenesis: Factors Inducing DNA Damage and Virus Integration. Cancers (Basel). 2014;6(4):2155-2186. doi:10.3390/cancers6042155

Rosa MI, Silva GD, de Azedo Simões PWT, et al. The Prevalence of Human Papillomavirus in Ovarian Cancer: A Systematic Review. International Journal of Gynecologic Cancer. 2013;23(3):437-441. doi:10.1097/IGC.0b013e318280f3e0

How to Cite

1.
Di Donna MC, Cucinella G, Solazzo MC, et al. Ovarian microbiota and Ovarian cancer: an overview and update meta-analysis. Acta Biomed. 96(3). doi:10.23750/abm.v96i3.16592

Issue

Section

REVIEWS CLINICAL ARTICLES, UPDATES, FOCUS ON

How to Cite

1.
Di Donna MC, Cucinella G, Solazzo MC, et al. Ovarian microbiota and Ovarian cancer: an overview and update meta-analysis. Acta Biomed. 96(3). doi:10.23750/abm.v96i3.16592