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Oral contraceptive and progestin-only use correlates to tissue tumor marker expression in women with cervical intraepithelial neoplasia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
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2012 (English)In: Contraception, ISSN 0010-7824, E-ISSN 1879-0518, Vol. 85, no 3, 288-293 p.Article in journal (Refereed) Published
Abstract [en]

Background: The study was conducted to investigate correlations between combined oral contraceptive (COC), any progestin-only contraceptive, medicated intrauterine device (MID) or systemic progestin-only (Syst-P) use and tumor marker expression in cervical intraepithelial neoplasia compared to nonusers.

Study Design: One-hundred ninety-five women of fertile age with cervical biopsies ranging histologically from normal epithelium to carcinoma in situ were recruited consecutively. Combined oral contraceptive, Syst-P and MID users were investigated according to the expression of 11 tumor markers.

Results: Overexpression of cyclooxygenase-2 (Cox-2) was observed in COC users, while interleukin 10 was underexpressed. When users of progestogen-only contraceptives were analyzed, there was a lower expression of cytokeratin 10 and interleukin 10. When only MID users were analyzed, a high expression of p53 was found. Expression of Cox-2, p53 and retinoblastoma protein differed between COC and MID users.

Conclusion: The study showed molecular alterations, which, in general, have not been studied previously in COC users and have never been studied in progestogen-only users. These biological events might be involved in epidemiological correlations found between hormonal contraceptive use and cervical neoplasms.

Place, publisher, year, edition, pages
2012. Vol. 85, no 3, 288-293 p.
Keyword [en]
Cervical intraepithelial neoplasia, Oral contraceptives, Gestagen, Medicated intrauterine device, Biological markers
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-171406DOI: 10.1016/j.contraception.2011.09.001ISI: 000300387500012OAI: oai:DiVA.org:uu-171406DiVA: diva2:511118
Available from: 2012-03-20 Created: 2012-03-19 Last updated: 2016-04-12Bibliographically approved
In thesis
1. Tissue tumor marker expression in normal cervical tissue and in cervical intraepithelial neoplasia, for women who are at high risk of human papilloma virus infection, are smokers, contraceptive users or in fertile age
Open this publication in new window or tab >>Tissue tumor marker expression in normal cervical tissue and in cervical intraepithelial neoplasia, for women who are at high risk of human papilloma virus infection, are smokers, contraceptive users or in fertile age
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aim of this research was to study the correlation between tissue tumor marker expression and HR-HPV infection, smoking, hormonal contraceptive use and sex steroids in women with cervical intraepithelial neoplasia or normal epithelium. The study investigated the expression of 11 tumor markers in cervical biopsies obtained from 228 women with different diagnoses ranging from normal cervical epithelium to various stages of CIN. 188 women were recruited at our colposcopy clinic (out-patient surgery, Department of Obstetrics and Gynecology, Falun Hospital) for laser cervical conization or a directed punch biopsy, either because of a vaginal smear (Pap smear) that showed cytological findings suggesting CIN, or because of repeated findings showing atypical squamous cells of undetermined significance (ASCUS). For 40 volunteers, punch biopsies were taken from the normal cervical epithelium. The time period for this study was 2005-2007.

Study I :  228 women, of whom 116 were tested, 64 were positive to HR-HPV. The results showed that Ki67 tumor cell proliferation index was the only marker that independently correlated to both the presence of HR-HPV and the severity of cervical lesions.

Study II:  228 women, of whom 83 were smokers (36, 9%). Smokers showed lower expression of p53, FHIT (tumor suppressor markers) and interleukin-10 .Higher expression of Cox-2 and Ki-67 (tumor proliferation markers).

Study III:  195 women who were premenopausal. There was increased p53 expression (tumor suppressor) in the progestin-IUD users compared to non-users. Decreased IL-10 expression (immunological marker) was observed in both COC users and any progestin-only users.

Study IV: Serum from 80 premenopausal women was available. The main finding was that the increased levels of serum progesterone and estradiol were associated with increased Cox-2 expression (proliferation marker). Serum progesterone and estradiol levels influence cellular and extracellular proteins which have been associated with neoplastic development in normal epithelium and CIN.

Conclusion: The results of these studies support previous epidemiological findings on the role of smoking, contraceptive use and sex steroids as co-factors in development of CIN and that tumor marker expression varies in different grades of CIN.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 74 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1137
tumor markers, cervical intraepithelial neoplasia, smoking, contraceptive use, sex steroid hormones, HPV infection
National Category
Health Sciences
Research subject
Obstetrics and Gynaecology
urn:nbn:se:uu:diva-262889 (URN)978-91-554-9348-6 (ISBN)
Public defence
2015-11-16, Rosénsalen, ingång 95/96, Akademiska sjukhuset, Uppsala, 13:00 (English)
Available from: 2015-10-21 Created: 2015-09-22 Last updated: 2015-10-27

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