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Gynaecological oncology

Basics, epidemiology and clinical aspects

Elevated levels of steroid hormones like estradiol and progesterone are important factors in the development of endometrial, breast and probably also ovarian cancer. Nevertheless, some medical interventions like hormone treatment for In Vitro Fertilization (IVF), Hormone Replacement Therapy (HRT) after menopause, and tamoxifen-treatment of breast cancer cause significant increases in steroid signaling. Therefore we are investigating whether transient changes (like observed in gonadotropin treatment for IVF), or sustained changes (as induced by HRT) in estradiol and/or progesterone signaling increase the relative risk for the above mentioned cancer types.  Furthermore, in our laboratory we are investigating the molecular mechanism behind the question why steroids are sometimes causing cancer development (increased estrogen signaling can cause endometrial cancer), while in other cases steroids seem to protect against cancer growth (progesterone inhibits estrogen induced carcinogenesis in the endometrium). In these investigations Wnt signaling plays an important role.

 

The life-time risk for infection with HPV is around 80%. Fortunately most women are able to clear this infection, and less than 10% of women infected with a high-risk HPV develop a persistent infection, which is one of the leading causes of preneoplastic and neoplastic lesions in the female genital tract, including cervical and vulvar intraepithelial neoplasia (CIN and VIN). Acquisition and clearing of HPV infection, viral load and persistence, T-cell response, cytokine expression, changes in cellular genome, viral oncogene proteins E6 and E7, role of human tumor suppressor genes p53 and Rb, loss of heterozygosity and telomerase activation are all factors that are studied to understand HPV-induced carcinogenesis. In addition to these molecular studies we are also investigating clinical aspects like the consequences of a national based primary screening program for cervical cancer and the role of HPV testing in the management of women with premalignant cervical lesions. Furthermore, in a number of randomized clinical trials alternative treatments, to otherwise mutilating surgery for VIN, are evaluated.

 

Besides the above more fundamental investigations, we are also involved in a great number of clinical studies after prevention, prediction, diagnosis, treatment and prognosis of a female urogenital tract disorders such as ovarian, uterine, cervical, vaginal and vulvar cancer. But also research after urinary and fecal incontinence is part of our scientific workload.

 

Best publication 2008

van Seters M, , van Beurden M, ten Kate FJ, Beckmann I, Ewing PC, Eijkemans MJ, Kagie MJ, Meijer CJ, Aaronson NK, Kleinjan A, Heijmans-Antonissen C, Zijlstra FJ, Burger MP, Helmerhorst TJ. Treatment of vulvar intraepithelial neoplasia with topical imiquimod. N Engl J Med. 2008;358:1465-73.

 

Publications 2007

Publications 2008

Publications 2009 

 

Personnel involved

Prof. Dr.Theo J Helmerhorst

Yongyi Wang

Leen J Blok

Lindy Santegoets

Annelinde Terlou  

Marielle Kocken

Regine Steegers-Theunissen

Yundan Jia           

Paul van der Horst