Anal cancer and vulvar cancer are relatively rare, but their incidence is increasing. Both cancers are preceded by high-grade precursor lesions, with over 5000 diagnoses in The Netherlands annually. These lesions commonly result from a high-risk human papillomavirus (HPV) infection. Whilst HPV vaccination is considered the long-term solution to cancer prevention, uptake is relatively low, HPV genotype coverage is incomplete and unvaccinated generations will never benefit from it.
Treatment of high-grade precursors provides an alternative effective means to prevent cancer. Most affected patients undergo multiple mutilating interventions, which are associated with severe psychosexual morbidity. The majority of these treatments are however unnecessary, as the risk of these precursors progressing to cancer is low (lifetime risk 10-30%). Hence, a biomarker enabling risk assessment of these cancer precursor lesions provides a solution to address the urgent clinical need of tailoring treatment and reducing overtreatment.
The project as awarded by KWF aims to clinically validate a biomarker test which demonstrated prognostic value for high-grade anal and vulvar precursors progressing to cancer in our previous research on large retrospective cohorts. This test is based on DNA methylation detection and developed by our consortium partner Self-screen BV as the PreCursor-M AnoGYN test (RUO).
The project will be a collaborative endeavor between Self-screen and Amsterdam UMC, led by PIs from the Departments of Pathology, Dermatology, Infectious Diseases, Data Science and Epidemiology and Center of Gynecological Oncology Amsterdam.
Clinical validation of the PreCursor-M AnoGYN methylation test for cancer risk stratification of high-grade anal and vulvar precursor lesions will take place in two ongoing nationwide prospective studies; MARINE for anal cancer precursors amongst men having sex with men living with HIV (MSMLWH) and VENUS for patients with vulvar cancer precursors. By means of a Delphi survey expert opinions will be collected to define clinical action thresholds and consensus follow-up and surveillance strategies. Lastly, the test will be validated in independent (inter)national prospective studies.
The expected outcome is that prospective validation and subsequent implementation of the PreCursor-M AnoGYN test will improve treatment guidance for affected patients. It will reduce the overtreatment of anal cancer precursor, with only test-positive patients requiring treatment, while test-negative patients will benefit from surveillance. In women with a test-negative vulvar cancer precursor, a conservative (non-radical) treatment may suffice given the low cancer risk in this group. This will alleviate the current unnecessary burden on the healthcare system and the patients, thereby improving quality of life.
Involved PI's
- Prof.dr. Renske Steenbergen (Pathology)
- Prof. dr. Henry de Vries (Dermatology)
- Dr. Maaike Bleeker (Pathology)
- Prof. dr. Jan Prins (Internal Medicine-Infectious Diseases)
- Prof. dr. Hans Berkhof (Epidemiology and Data Science)
KWF PPP Pilot
PPP stands for public-private partnership and concerns collaborations between research organizations and industry. The PPP innovation scheme aims to stimulate public-private partnerships for research that creates economic and societal impact. KWF has been given the opportunity to participate in the Health~Holland PPP Pilot of 2024. The purpose of this pilot is to allow parties to gain experience with the structure of the new PPP innovation scheme that has been in effect since this year. This amended scheme includes, among other things, new financing conditions.