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Jonsson, S. (2023). Pelvic inflammatory disease and epithelial ovarian tumors. (Doctoral dissertation). Umeå: Umeå University
Open this publication in new window or tab >>Pelvic inflammatory disease and epithelial ovarian tumors
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Bäckeninflammation och epiteliala ovarialtumörer
Abstract [en]

Background: Epithelial ovarian cancer and borderline ovarian tumors consist of several histotypes in which high-grade serous carcinoma is the most common. The majority of epithelial ovarian tumors are considered to originate in the fimbriated end of the fallopian tubes. What initiates these tumors is far from completely understood. Pelvic inflammatory disease has been proposed as a modifiable risk factor for epithelial ovarian tumors. A major cause of pelvic inflammatory disease is Chlamydia trachomatis which has been shown to have cancer-causing potential. The overall purpose of this thesis was to study associations of pelvic inflammatory disease and C. trachomatis with risk of epithelial ovarian tumors.

Methods: In a cross-sectional study (Paper I) we collected ovarian tissue and corresponding blood samples from 69 women undergoing surgery due to suspected ovarian pathology. C. trachomatis specific protein (immunohistochemistry) and C. trachomatis DNA (qPCR) in ovarian tissue were analyzed (Paper I). In a nested case-control study (Paper II) prospective blood samples from 92 women diagnosed with high-grade serous ovarian cancer were matched to four controls each for age and date of plasma sampling. C. trachomatis specific plasma antibodies were analyzed by commercial Enzyme-Linked ImmunoSorbent Assay (ELISA) and Micro-ImmunoFluorescence (MIF) (Paper I and Paper II). We performed a nationwide register-based case-control study where we included 15 072 women diagnosed with epithelial ovarian cancer (Paper III), 4782 women diagnosed with borderline ovarian tumors (Paper IV), and ten controls each matched for age and residential district. Using national Swedish registers, we retrieved data on historyof pelvic inflammatory disease and the potential confounding factors parity, educational level, previous gynecological surgery, and hormonal therapy.

Results: We found C. trachomatis DNA in ovarian tissue of eight women with ovarian carcinoma, but not in ovarian tissue from women with borderline ovarian tumors or benign disease (Paper I). The prevalence of the C. trachomatis specific protein did not differ in benign and malignant tissue (Paper I). Prevalence of C. trachomatis specific plasma antibodies was similar in cases and controls at diagnosis (Paper I) and prospectively (Paper II). A history of clinically verified pelvic inflammatory disease was associated with an increased risk of epithelial ovarian cancer overall (Paper III) and borderline ovarian tumors overall (Paper IV). Histotype-specific analyses showed an increased risk of serous carcinoma (Paper III), high-grade serous carcinoma (Paper III), clear cell carcinoma (Paper III), and serous borderline ovarian tumors (Paper IV) but not significantly with other histotypes. A dose-response relationship was seen between an increased number of pelvic inflammatory disease episodes and epithelial ovarian cancer (Paper III), as well as borderline ovarian tumors (Paper IV).

Conclusions: This thesis contributes to an improved understanding of the association between pelvic inflammatory disease and epithelial ovarian tumors. The results regarding C. trachomatis are inconclusive and suggests that the association of pelvic inflammatory disease with epithelial ovarian tumors acts through mechanisms other than Chlamydia alone.

Abstract [sv]

Bakgrund: Epitelial ovarialcancer och ovariella borderlinetumörer består av flera histotyper där höggradigt seröst karcinom är den vanligaste. Majoriteten av epiteliala ovarialtumörer anses ha sitt ursprung i äggledarnas yttersta del, men vad som initierar dessa tumörer är inte klarlagt. Bäckeninflammation har föreslagits vara en modifierbar riskfaktor. Chlamydia trachomatis har visats ha cancerframkallande egenskaper och är en viktig orsak till bäckeninflammation. Syftet med denna avhandling var att studera om C. trachomatis och bäckeninflammation har samband med risk för epiteliala ovarialtumörer.

Metod: I en tvärsnittsstudie samlades ovarialvävnad och blodprover från 69 kvinnor som genomgått operation på grund av misstänkt sjukdom i äggstocken (Studie I). C. trachomatis-specifikt protein (immunhistokemi) och C. trachomatis-DNA (qPCR) analyserades i ovarialvävnad. I en nestad fall-kontroll studie analyserades prospektiva blodprover från 92 kvinnor som diagnostiserats med höggradigt serös ovarialcancer, samt prover från fyra kontroller vardera matchade med avseende på ålder och datum för provtagning (Studie II). C. trachomatis-specifika plasmaantikroppar analyserades med hjälp av ELISA (Enzyme-Linked ImmunoSorbent Assay) och MIF-analyser (Micro-ImmunoFlourescence) (Studie I och Studie II). I en rikstäckande registerbaserad fall-kontroll studie inkluderades 15 072 kvinnor som diagnostiserats med epitelial ovarialcancer (Studie III) och 4 782 kvinnor som diagnostiserats med borderlinetumörer (Studie IV) samt tio kontroller per fall som matchades med avseende på ålder och boendedistrikt. Från nationella svenska register hämtades uppgifter om tidigare bäckeninflammation och de potentiella förväxlingsfaktorerna paritet, utbildningsnivå, tidigare gynekologisk kirurgi och hormonell behandling.

Resultat: C. trachomatis-DNA identifierades i ovarialvävnad från åtta kvinnor med ovarialcancer, men inte i ovarialvävnad från kvinnor med borderlinetumörer eller godartade ovarialtumörer. Förekomsten av det C. trachomatis-specifika proteinet skiljde sig inte åt mellan godartad, borderline eller malign vävnad. Prevalensen av C. trachomatis-specifika plasmaantikroppar var likartad hos fall och kontroller såväl vid diagnos som prospektivt. En historia av bäckeninflammation var associerad med en ökad risk för epitelial ovarialcancer och borderlinetumörer. Histotypspecifika analyser visade en ökad risk för serösa, höggradigt serösa och klarcells karcinom samt serösa borderlinetumörer men inte signifikant med andra andra histotyper. Ett dos-respons förhållande sågs för antal episoder av bäckeninflammation och risk för epitelial ovarialcancer samt borderlinetumörer.

Slutsats: Denna avhandling bidrar till en förbättrad förståelse av sambandet mellan bäckeninflammation och epiteliala ovarialtumörer. Resultaten avseende C. trachomatis är inte entydiga och tyder på att sambandet mellan bäckeninflammation och epiteliala ovarialtumörer medieras genom andra mekanismer än enbart C. trachomatis.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2023. p. 65
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2242
National Category
Obstetrics, Gynecology and Reproductive Medicine Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-208116 (URN)978-91-8070-051-1 (ISBN)978-91-8070-052-8 (ISBN)
Public defence
2023-06-02, Hörsal B, Målpunkt T, byggnad 1D 9 trp, Norrlands universitetssjukhus, Umeå, 13:00 (Swedish)
Opponent
Supervisors
Funder
Cancerforskningsfonden i NorrlandRegion VästerbottenUmeå University
Available from: 2023-05-12 Created: 2023-05-09 Last updated: 2023-05-10Bibliographically approved
Jonsson, S., Jonsson, H., Lundin, E., Häggström, C. & Idahl, A. (2023). Pelvic inflammatory disease and risk of epithelial ovarian cancer: a national population-based case-control study in Sweden. American Journal of Obstetrics and Gynecology, 230(1), 75.e1-75.e15
Open this publication in new window or tab >>Pelvic inflammatory disease and risk of epithelial ovarian cancer: a national population-based case-control study in Sweden
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2023 (English)In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 230, no 1, p. 75.e1-75.e15Article in journal (Refereed) Published
Abstract [en]

Background: Epithelial ovarian cancer is an insidious disease, and women are often diagnosed when the disease is beyond curative treatment. Accordingly, identifying modifiable risk factors is of paramount importance. Inflammation predisposes an individual to cancer in various organs, but whether pelvic inflammatory disease is associated with an increased risk of epithelial ovarian cancer has not been fully determined.

Objective: This study aimed to investigate a possible association between clinically verified pelvic inflammatory disease and the risk of epithelial ovarian cancer.

Study Design: In this national population-based case-control study, all women in Sweden diagnosed with epithelial ovarian cancer between 1999 and 2020 and 10 controls for each were identified, matched for age and residential district. Using several Swedish nationwide registers, data on previous pelvic inflammatory disease and potential confounding factors (age, parity, educational level, and previous gynecologic surgery) were retrieved. Adjusted odds ratios and 95% confidence intervals were estimated using conditional logistic regression. Histotype-specific analyses were performed for the subgroup of women diagnosed with epithelial ovarian cancer between 2015 and 2020. Moreover, hormonal contraceptives and menopausal hormone therapy were adjusted in addition to the aforementioned confounders.

Results: This study included 15,072 women with epithelial ovarian cancer and 141,322 controls. Most women (9102 [60.4%]) had serous carcinoma. In a subgroup of cases diagnosed between 2015 and 2020, high-grade serous carcinoma (2319 [60.0%]) was identified. A total of 168 cases (1.1%) and 1270 controls (0.9%) were diagnosed with pelvic inflammatory disease. Previous pelvic inflammatory disease was associated with an increased risk of epithelial ovarian cancer (adjusted odds ratio, 1.39; 95% confidence interval, 1.17–1.66) and serous carcinoma (adjusted odds ratio, 1.46; 95% confidence interval, 1.18–1.80) for the entire study population. For the subgroup of women diagnosed in 2015–2020, pelvic inflammatory disease was associated with high-grade serous carcinoma (adjusted odds ratio, 1.43; 95% confidence interval, 1.01–2.04). The odds ratios of the other histotypes were as follows: endometrioid (adjusted odds ratio, 0.13; 95% confidence interval, 0.02–1.06), mucinous (adjusted odds ratio, 1.55; 95% confidence interval, 0.56–4.29), and clear cell carcinoma (adjusted odds ratio, 2.30; 95% confidence interval, 0.90–5.86). A dose-response relationship was observed between the number of pelvic inflammatory disease episodes and the risk of epithelial ovarian cancer (Ptrend<.001).

Conclusion: A history of pelvic inflammatory disease is associated with an increased risk of epithelial ovarian cancer and a dose-response relationship is evident. Histotype-specific analyses show an association with increased risk of serous epithelial ovarian cancer and high-grade serous carcinoma and potentially also with clear cell carcinoma, but there is no significant association with other histotypes. Infection and inflammation of the upper reproductive tract might have serious long-term consequences, including epithelial ovarian cancer.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
epithelial ovarian cancer, high-grade serous carcinoma, ovarian cancer, pelvic inflammatory disease, population-based case-control study
National Category
Obstetrics, Gynecology and Reproductive Medicine Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-216205 (URN)10.1016/j.ajog.2023.09.094 (DOI)37778677 (PubMedID)2-s2.0-85175294490 (Scopus ID)
Available from: 2023-11-06 Created: 2023-11-06 Last updated: 2024-01-05Bibliographically approved
Jonsson, S., Lundin, E., Elgh, F., Ottander, U. & Idahl, A. (2020). Chlamydia trachomatis and Anti-MUC1 Serology and Subsequent Risk of High-Grade Serous Ovarian Cancer: A Population-Based Case-Control Study in Northern Sweden. Translational Oncology, 13(1), 86-91
Open this publication in new window or tab >>Chlamydia trachomatis and Anti-MUC1 Serology and Subsequent Risk of High-Grade Serous Ovarian Cancer: A Population-Based Case-Control Study in Northern Sweden
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2020 (English)In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 13, no 1, p. 86-91Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Chlamydia trachomatis salpingitis causes inflammatory damage to the fallopian tube and could potentially cause initiation and progression of high-grade serous ovarian cancer (HGSC). Furthermore, C. trachomatis infection may stimulate mucin 1 (MUC1) protein production, possibly affecting anti-MUC1 antibody levels. The aim of this study was to examine if serology indicating past infection with C. trachomatis as well as anti-MUC1 production was associated with subsequent risk of HGSC.

MATERIALS AND METHODS: In a prospective nested case-control study within the Northern Sweden Health and Disease Study and the Northern Sweden Maternity Cohort, the prevalence of chlamydial and anti-MUC1 antibodies was analyzed in blood samples drawn more than one year before diagnosis from 92 women with HGSC and 359 matched controls. Matching factors were age, date at blood draw, and sampling cohort. Plasma C. trachomatis IgG was analyzed using commercial micro-immunofluorescence test; chlamydial Heat Shock Protein 60 IgG (cHSP60) and anti-MUC1 IgG were analyzed with ELISA technique.

RESULTS: The prevalence of C. trachomatis IgG and cHSP60 IgG antibodies, as well as the level of anti-MUC1 IgG was similar in women with HGSC and controls (16.3% vs. 17.0%, P = 0.87; 27.2% vs. 28.5%, P = 0.80; median 0.24 vs. 0.25, P = 0.70). Anti-MUC1 IgG and cHSP60 IgG levels were correlated (r = 0.169; P < 0.001).

CONCLUSIONS: The findings of this prospective nested case-control study did not support an association between C. trachomatis infection, as measured by chlamydial serology, or anti-MUC1 IgG antibodies, and subsequent risk of HGSC.

Place, publisher, year, edition, pages
Elsevier, 2020
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-174272 (URN)10.1016/j.tranon.2019.09.007 (DOI)000502822300010 ()31805519 (PubMedID)2-s2.0-85075720208 (Scopus ID)
Available from: 2020-08-19 Created: 2020-08-19 Last updated: 2023-05-10Bibliographically approved
Jonsson, S., Jonsson, H., Lundin, E., Häggström, C. & Idahl, A.Inflammatory disease and epithelial ovarian cancer risk: a national population-based case-control study in Sweden.
Open this publication in new window or tab >>Inflammatory disease and epithelial ovarian cancer risk: a national population-based case-control study in Sweden
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(English)Manuscript (preprint) (Other academic)
Keywords
EOC, epithelial ovarian cancer, HGSC, high-grade serous carcinoma, ovarian cancer, pelvic inflammatory disease, PID, population-based case-control study
National Category
Obstetrics, Gynecology and Reproductive Medicine Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-208132 (URN)
Funder
Umeå University
Available from: 2023-05-10 Created: 2023-05-10 Last updated: 2023-05-10
Jonsson, S., Jonsson, H., Lundin, E., Häggström, C. & Idahl, A.Pelvic inflammatory disease and risk of borderline ovarian tumors: a national population-based case-control study in Sweden.
Open this publication in new window or tab >>Pelvic inflammatory disease and risk of borderline ovarian tumors: a national population-based case-control study in Sweden
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(English)Manuscript (preprint) (Other academic)
Keywords
BOT, borderline ovarian tumor, serous BOT, pelvic inflammatory disease, PID, population-based case-control study
National Category
Obstetrics, Gynecology and Reproductive Medicine Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-208135 (URN)
Funder
Umeå University
Available from: 2023-05-10 Created: 2023-05-10 Last updated: 2023-05-10
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0009-0005-1288-4645

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