Gynaecology and Gynaecologic Oncology

According to the World Health Organization, cervical cancer should become a rare disease worldwide by the end of the century by increasing  screening and vaccination uptake to respectively 70 and 90%. In the Netherlands the uptake is around 50 and 55%. In the Erasmus MC we have a special population with HIV and organ transplantation who are at risk for developing cervical cancer.

Subtheme 1.1 Organ transplantation and cervical pre-malignancies.

Patients after organ transplantation have a higher chance of pre-malignancies of the cervix due to immunosuppressive drugs. Many women develop cervical premalignancy after transplantation and are often resistant for treatment.

The student will study the relation between solid organ transplantation (long, liver, kidney), the different immunosuppressive drugs and presence of HPV in these women. The main research question is: Should women receive HPV vaccination prior to organ transplantation?

Please contact h.vanbeekhuizen@erasmusmc.nl

Subtheme 1.2 Adjuvant HPV vaccination in treatment for HSIL of the vulva

Recently we received a KWF grant for a RCT on adjuvant vaccination in women with HSIL (a precursor lesion of HPV-related vulvar cancer). In this international multicentre randomized double blinded RCT there are many opportunities for research masters to participate.

In the Netherlands every year 300 women are diagnosed with vulvar HSIL. As with other HPV related (pre) malignancies, the incidence has been rising over the past 20 years. The peak incidence of these premalignant lesions of the vulva lies between 35 and 40 years of age. Multiple treatment methods for vulvar HSIL are available for these woman, including surgery, laser vaporization, and topical imiquimod, all with comparable treatment success. Despite treatment, at least 30% of women will develop a recurrence within 2 years, with a much higher lifetime risk of recurrence. This results in multiple treatments with sometimes disfiguring effects and associated negative psychosocial and psychosexual impact. Woman with vulvar HSIL have a lifelong increased risk of vulvar cancer, and approximately 10% of women with (treated) vulvar HSIL will develop vulvar cancer within 10 years of first diagnosis.

To date, a successful strategy for reduction of recurrences of HSIL has not been established. The available evidence on the use of adjuvant HPV vaccination in the treatment of vulvar HSIL is rising with hopeful results, yet insufficient to guide clinical practice. There is limited data that shows that prophylactic HPV vaccination after treatment of vulvar HSIL reduces the chance of recurrence, therefore leading to a reduction in repeated (surgical) interventions. There are no randomized controlled studies supporting this data.

We will investigate the rate of recurrences of vulvar HSIL at 24 months in women treated for vulvar HSIL with concurrent nonavalent HPV vaccination versus placebo

Please contact r.vandelaar@erasmusmc.nl

In this research theme we study the effect of our surgery. Especially in vulvar cancer we tend to do less radical surgery in order to spare the function of the vulva.

Subtheme 2.1 How do preoperative tumor characteristics relate to the presence of a tumor positive sentinel node? Development of a prediction model.

In recent decades the treatment of early stage vulvar cancer has changed to performing the sentinel node procedure to detect groin metastases in selected cases, as opposed to a complete inguinal lymph node dissection as done in the past and in high risk cases.

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Vulvar cancer patients are eligible for a sentinel node procedure in case: tumor FIGO T1, less than 4 cm, squamous cell cancer with a depth of invasion more than 1 mm and clinically non- suspicious inguinofemoral lymph nodes.

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Currently the protocol recommends complete node dissection in case the sentinel node is not visible on the preoperative lymph node scintigraphy, or when the node is not found during surgery, when exploring the groin, regardless of the a- priority risk of positive lymph node status. In daily practice we might act differently; based on the size, the depth of tumor infiltration and the presence of poor prognostic signs we can discuss with the patients to omit a complete inguinal node dissection when the sentinel node procedure fails. (experience based).

Only in older papers and in the classical text books do we find any information about the relationship between tumor infiltration depth and the probability to find a positive inguinal node. These data refer to the time that a complete node dissection was performed in all vulvar cancer patients and it is unclear how patients were selected for these studies. There is no information on the relationship between preoperative tumor infiltration (and other factors) and positive or negative sentinel nodes in patients eligible for the sentinel node procedure. Nor do we know the relationship between the postoperative assessment of the vulvar tumor and the status of the sentinel node in this patient group.

The main aim of the study is to establish the relationship between pre- and postoperative findings and to create a prognostic model based on simple and unambiguous clinical and pathological parameters.

The first step is a retrospective cohort study, including all women treated at the Erasmus MC for primary vulvar cancer from 2005-2021 to develop such a model that predicts the presence of a positive sentinel node. Validation of this model can be done in two prospective, well documented databases, i.e., of the GROINSS_V studies.

Please contact h.vandoorn@erasmusmc.nl

Subtheme 2.2  Can we reduce the sentinel node assessment burden for the pathologist, without compromising oncological outcome? 

The histopathological criteria for assessment of the sentinel nodes are well described (see textbox). The number of slides to be assessed varies enormously, since the number of nodes retrieved per groin can range from 1 – 6. The burden for the pathology department is therefore high. Strict assessment is mandatory; even in the case of single cell node metastases, additional treatment is advised, therefore we would not easily change the protocol. There is however no knowledge about the contribution of each step in the protocol to the final diagnosis of node metastases, or whether a comprehensive assessment can be omitted in certain cases.

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The standard protocol for pathologic assessment of the sentinel node(s):

Briefly, the sentinel nodes are cut in the middle, subsequently, four sections are cut from every half for hematoxylin and eosin (HE)staining (routine histopathologic examination). Ultrastaging is performed only on sentinel nodes that are negative on routine histopathologic examination. For ultrastaging, additional pairs of sections are cut with three sections per millimeter. One section of each pair is stained with HE, and the other section is immunostained with cytokeratin.

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The aim of this study is to assess the contribution of each step in the procedure and to find ways to reduce the burden for the pathology department.

The first step is to establish what each part of the histopathological process contributes to determining nodal status. Second, there should be an analysis of the actual costs, as well as a process analysis to see how efforts and cost can be reduced.

Please contact h.vandoorn@erasmusmc.nl

In this research theme, we study the effectiveness of methods for (early) patient diagnosis, and for the evaluation of quality of our care.

Subtheme 3.1 How can we optimally use hyperspectral imaging (HSI) in our operating room workflow, before the surgery to delineate surgical plans or after the surgery to check surgical margins?

Adequate tumor recognition is crucial in gynecological oncology. For example, during vulvar cancer surgery, this plays a role in selecting surgical margins that ensure full tumor removal and minimal mutilation from excessive removal of healthy tissues. As a second example, during ovarian cancer surgery, in case of peritoneal carcinomatosis, this plays a role in determining which spots to remove and which spots to leave behind. Facilitating optimal decision-making during these complex tasks with image-guided tumor recognition would be invaluable.

Hyperspectral imaging is a novel imaging technique available in our department that provides a comprehensive view of tissue characteristics by capturing a wide range of spectral information. With this technology, we are currently developing AI-based software that enables surgeons to differentiate between healthy and diseased tissue with exceptional precision, aiding in the identification of tumour margins and enhancing the accuracy of surgical resections.

The aims of this study are: 1) to help us with the collection of more HS images during gynecological oncology surgeries (AI outcome improves with quantity and quality of data), 2) to assist in accurate image segmentation together with gynecological oncologists and pathologists, and 3) to evaluate data acquisition processes and contribute to the development of a protocol for effective camera use, with minimal impact on standard surgical procedures.

Please contact n.vandeberg@erasmusmc.nl