The research within our LUMC departments is conducted within departmental research programmes. The research programme below is embedded within the department of Gynaecology.
Aim and focus
The main focus of this research line lies on the holistic approach towards diseases of the female genital tract. It aims to bridge the results of basic and translational research, new surgical techniques & technologies and to evaluate and improve quality of life after treatment for gynaecological (cancer) diseases into daily practice. Moreover, the main goal of the research is valorisation of these results.
The translational research on HPV induced neoplasms (cervix and vulva) and ovarian and endometrial cancer as well, is ongoing due to continuous supply of bio data (tissue) to laboratories (pathology, clinical immunology, genetics). New approaches of surgery are analysed and implemented in daily practice. The department of Gynaecology of the LUMC is a well-known national and international referral hospital for patients with gynaecological cancers, because of the well-recognized immunotherapy trials using the HPV16-SLP vaccine. Furthermore, quality assessment studies upon surgery (nerve sparing, image guided and evaluation of surgical care) with its development of evaluation of surgical techniques that allow autonomic nerve and/or fertility preservation, are well recognized.
Specific aims of the research programme are:
- Local tumor spread of cervical cancer and prognosis
- The evaluations of mechanisms that leads to immune escape
- Immune-status and effective and safe strategies to achieve long-term preventive and therapeutic T-cell immunity against HPV-infection and related disorders such as cervical cancer
- To develop new immunotherapeutic treatments for patients with HPV-induced neoplasias (cervix and vulva)
- Surgical methods and techniques that can optimize the treatment of cervical cancer and endometriosis, with a focus on down-staging and improving quality of life, such as surgical staging in the pelvis, minimally invasive surgery and nerve sparing operations, and fertility sparing techniques with a focus on cryopreservation of ovarian tissue
- Sequelae of oncology treatment regarding sexual function, bladder function and health related quality of life.
- Special focus is on implementation of new surgical techniques and technologies in Minimally Invasive Surgery, both in oncological as benign indications. The latter is in close cooperation with the technical University Delft (Medical Delta). Quality assessment-and implementation studies are rolled out.
- Cryopreservation of ovarian tissue for women starting chemotherapy.
Position in international context
There is a close cooperation with European centres in Leuven, Institute Pasteur Paris, Cambridge and Cardiff. Within the Medical Delta group , with the Technical University of Delft, studies on new techniques and implementing new technologies in minimally invasive surgery are well recognized . In addition, research is done in close cooperation with Harvard Medical School (Brigham & Women’s Hospital, Boston).
There is major international interest in the Leiden operating technique to spare the autonomous nerves in the pelvis during radical hysterectomy for cervical cancer. The same is true for the techniques developed for fertility preservation in cervical and endometrial cancer.
Furthermore, the research has established long standing cooperation with key institutes in high-risk areas for cervical cancer. The epidemiology of HPV has been analysed worldwide (Indonesia, Suriname). Escape mechanisms to immune elimination by various HPV types, the feasibility of tumour prevention and down-staging and the possibility of HPV vaccination are also addressed on a larger scope.
The LUMC is one of the first centres in the world to perform clinical studies on therapeutic vaccines in women with HPV-induced (pre)cancers.
Content / highlights / achievements
- We have demonstrated the safety and high immunogenicity of the synthetic long peptide vaccine against the HPV16 oncoproteins E6 and E7 (ISA101) in patients with different stages of HPV-induced neoplasia
- The clinical efficacy of ISA101 in two independent clinical trials in patients with HPV-induced vulvar intraepithelial neoplasia
- We have determined the synergism of standard chemotherapy and ISA101 in patients with metastatic cervical cancer
- We have studied the safety of nerve- and fertility preserving (surgical) techniques in gynaecological cancer in general and cervical cancer specifically
- A laboratory model to assess sexual function by plethysmography of vaginal blood flow, indicative of vaginal lubrication. With this model the relation between autonomous pelvic nerve damage and sexual function is studied in patients
- We have developed an operating technique to spare the pelvic autonomous nerves during radical hysterectomy
- We have developed a program to study the learning of surgical skills and implementation of/in minimally invasive surgery
- Quality indicators are developed for implementing new techniques in MIS
- We have developed a cryopreservation program of ovarian tissue at risk due to cytostatic treatment and studied the acceptance and expectations of this method among patients and doctors.
- The translational research line will be in the same scope of HPV related tumours and will focus on vulvar (pre)cancers.
- Clinical vaccination studies will be extended to larger phase II and phase III trials in patients with HPV-related neoplasias as single treatment or as combination treatment with chemotherapy or checkpoint inhibitors. The use of adoptive cell therapy in patients with metastatic cervical cancer will be explored. The tumour biology of cervical cancer relative to local tumour spread and growth will be studied in a well-documented group of patients operated for locally advanced cervical cancer. The see-and –treat projects in Indonesia and Surinam to prevent and down-stage cervical cancer will be improved and continued as these projects provide the most valuable tissue, cytology and blood samples for basic immunological research.
- Additional basic and translational research will be aimed at endometrial cancer being a part of the BRCA-cancer syndrome.
- For the surgical research part the future themes will focus on optimal and most effective approach to surgery on the female genital tract. Image guided surgery for gynaecological cancer (ovarian, endometrium) as well as endometriosis, radicality of oncologic surgery (SHAPE study), cryo preservation of ovarian tissue and quality assessment studies (Qusum study for endometriosis surgery) are started. Future research on patient safety engineering are in close corporation with the TUD and in progress. Themes are OR of the future, DORA 2.0 and living lab.
- The proof of principle of nerve sparing and fertility sparing surgery in cervical cancer will be further pursued, the studies on cost-benefit aspects of minimal invasive surgery will be expanded just like the research to transplant and cryopreserve ovarian tissue to prevent damage to ovarian function due to oncological treatment.
Cohesion within LUMC
Departments of Medical Oncology, Pathology, Anatomy (nerve sparing), Genetics, Radiotherapy, Neurology (sexual function laboratory), Clinical Epidemiology and Medical Decision Making. Collaboration with CHDR.
Active participation in the research profile areas of Cancer, Pathogenesis & Therapy (CPT) and IHCQ