Gynaecology 1

Cervix cancer

Principal investigators

Prof.Dr J.B.Trimbos, Prof.Dr G.G.Kenter, Prof.Dr A.A.W.Peters

Aim and focus

• local tumor spread of cervical cancer and prognosis
• mechanisms leading 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  
• surgical methods and techniques that can be used in the treatment of cervical cancer 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
• sequelae of oncology treatment regarding sexual function

Position in international context

This project has established long standing cooperation with key institutes in high-risk areas for cervical cancer and analyzes the epidemiology of HPV on a world-wide scale. Escape mechanisms to immune elimination by various HPV types, the feasibility of tumor prevention and down-staging and the possibility of HPV vaccination are also addressed on a larger scope.

The LUMC is one of the first centers in the world to perform clinical studies on therapeutic vaccines in women with cervical cancer. There is close cooperation with European centers in Leuven, Institut Pasteur Paris, Jena, Cambridge and Cardiff.  Within the Medical Delta group there is close collaboration with the Technical University of Delft to study techniques and methods in minimally invasive surgery. There is major international interest in the Leiden operating technique to spare the autonomous nerves in the pelvis during radical hysterectomy.

Content/ highlights/ achievements

• The detection of memory T-helper responses to E2 and E6 in of healthy individuals but less in CIN and cervical cancer patients, suggesting that these T-cells play an important role against persisting HPV infection and subsequent malignant development
• Phase I studies with peptides from the E6 and E7 HPV16 region and T-helper peptides  showed no toxicity > grade II. A potent response of HPV16 specific T-cells was found after vaccination.
• 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.
• An operating technique to spare the pelvic autonomous nerves during radical hysterectomy
• A program to study the learning of surgical skills and implementation of/in minimally invasive surgery.

Future themes

Clinical vaccination studies will be extended to phase II trials in HPV related malignant disease and in healthy volunteers. The tumor biology of cervical cancer relative to local tumor 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 advanced as these projects provide most valuable tissue, cytology and blood samples for basic immunological research. The proof of principle of nerve sparing surgery in cervical cancer will be further pursued, the studies on cost-benefit aspects of minimal invasive surgery will be expanded and the same is true for research to transplant and cryopreserve ovarian tissue to prevent damage to ovarian function due to oncological treatment.

Cohesion within LUMC

Departments of Pathology, Immuno-Haematology, Anatomy (nerve sparing), Neurology (sexual function laboratory) and Clinical Epidemiology.