Short summary

The projects aims to investigate the presence of bacterial and viral DNA in fallopian tube tissue with premalignant (STIC) lesions and compare findings to a control group of health fallopian tube tissue. The overall aim is to investigate the potential role of microbiologial agents in the development of ovarian cancer. 

Rationale

EOC is a major threat to female health, with a global prevalence of 239,000 cases in 2012. Mortality is high due to the late onset of symptoms and the resulting disseminated disease at presentation.  Almost 90% of ovarian cancers originate from epithelial cells. Historically these were thought to arise from the surface mesothelial lining of the ovaries. However, recent research has revealed that a large proportion of serous EOC originate in precancerous lesions called serous tubal intraepithelial carcinomas (STICs) located in the fimbriated end of the fallopian tubes. 

There is an increasing focus on the role of infectious agents in human carcinogenesis. It has been estimated that 20% of the global cancer burden is attributed to infectious causes. In view of the lacking understanding of EOC etiology, and the fact that the female internal genitalia are directly accessible to outside pathogens, it is relevant to consider a potential role of infectious agents in ovarian carcinogenesis. 

Data from several studies indicate that factors that hinders the passage through the female genital tract, such as tubal ligation or hysterectomy, are associated with a decreased risk of EOC. More support for the infection theory is gained in epidemiological studies that have demonstrated that women with tubal factor infertility have a higher risk of EOC. Some studies have also found a higher risk of EOC among patients with previous reported episodes of PID. However, these findings are controversial since other studies do not confirm these associations. Specific infectious agents such as EBV, CMV, Chlamydia trachomatis and Mycoplasma genitalium have been observed in EOC tissues, but results are conflicting and the available studies are scarce. If an infectious agent is involved in OC tumorigenesis, focus could shift from the current extensive regimes of surgery and chemotherapy towards preventive measures such as vaccines. Therefore, more data is urgently needed. To the best of our knowledge, and based upon our recently published review article, no previous studies have investigated the prevalence of microbiological DNA/RNA in fallopian tube tissue with STIC lesions. If there is an infectious etiology to EOC, we suspect conditions are more advantageous for the identification of microbiological genetic material in STIC lesions since they predate tumor formation and since the structural integrity of the tissue is relatively more intact. 

Description of the cohort

The case group will consist of fallopian tube tissue blocks with STIC lesions.

The control group will consist of fallopian tube tissue blocks with normal tissue 

Data and biological material

In addition to the aforementioned tissue blocks, relevant information from the patients medical files will be collected to allow for confounder control in the study. 

Collaborating researchers and departments

Dept. of Gynecology, Odense University Hospital

• Professor Jan Blaakær

Dept. of Pathology, Odense University Hospital

• Consultant Doris Schledermann

Dept. of Pathology, Herlev Hospital

• Professor Estrid Högdall

Dept. of Gynecology, Copenhagen University Hospital

• Professor Claus Högdall

Dept. of Gynecology, Copenhagen University Hospital

• Consultant, phd. Tine Schnack

Publications associated with the project

Ingerslev, Kasper, et al. "High-risk HPV is not associated with epithelial ovarian cancer in a Caucasian population." Infectious agents and cancer 11.1 (2016): 39.

Ingerslev, Kasper, et al. "The potential role of infectious agents and pelvic inflammatory disease in ovarian carcinogenesis." Infectious agents and cancer 12.1 (2017): 25.