Publishable Summary - M30 - May 2015

Project context and objectives

Cervical cancer (CC) is the second most common malignancy in women worldwide. While epidemiologists at the recent IGCS meeting in Melbourne (Nov 2014) judged that HPV was eradicable if women were screened worldwide, the reality is that regular screening for all can presently not be reinforced in highly endemic areas (such as India, Africa and Certain areas in South America) where 4/5th of the population at risk may not be aware of screening practices.

Although CC is a single diagnostic entity and infection of high-risk HPV is recognized as an important initiating event in tumorigenesis, CC exhibits differences in clinical behaviour. Stratification of CC into subclasses for progression and response to targeted treatment remains to be defined. At present, the dominant targets under scrutiny for innovative CC treatments are the following: EGFR/PI3K pathway, proliferation/DNA checkpoint and angiogenesis inhibition as well as anti-HPV vaccines. There have been recent publications (Ojesina, 2014; Wright, 2013) on high resolution genetic investigations in CC. So far, there has been no prospective assessment on patient outcome based on whole genome/exome sequencing or protein profiling of their tumors together with quality control evaluation of patient treatment. Early prospective data is available from a small phase 2 clinical trial by Institut Curie, the coordinators’ center, suggesting that EGFR inhibition at the membrane is ineffective in the presence of a downstream PI3K pathway activation (de la Rochefordière et al., 2015).


  • We are lacking prognostic and predictive biomarkers for CC treatment and there is a growing need for the development of biomarkers to follow up the course of the disease.

RAIDs is a multidisciplinary co-operation between academic clinical centers, SMEs and translational research platforms. It combines Next Generation Sequencing (NGS) and Reverse Phase Protein array (RPPA) in a large patient population prior to standard therapy. It includes:
▪ a cognitive cohort study (BioRAIDs) intended to define tumor stratification for targeted therapies,
▪ as well as precision medicine trials using an HPV directed vaccine in combination with checkpoint inhibition.
In addition, high throughput screening techniques have been performed in CC cell lines, allowing to identify new drugs of relevance for advanced stage multi resistant CC. These molecules are to be validated in preclinical mouse models. Ongoing studies will assess in vitro efficacy of drug targeting according to molecular phenotypes.


The main objectives of RAIDs as stated in the DoW are:

  • To identify prognostic and predictive biomarkers for standard and innovative therapies in cervical cancer patients using both high throughput genomic and proteomic approaches, the final aim being to improve treatment response for the individual patient;
  • To define a set of stratification criteria for therapy in patients with cervical cancer based on the tumor’s molecular profile;
  • To identify underlying mechanisms causing immune tolerance of this sexually transmitted viral disease in order to facilitate innovative clinical interventions by vaccination studies (together with micro-environment modulators and/or checkpoint inhibitors);
  • To improve clinical outcome of patients with cervical cancer by conducting interventional precision medicine trials. Clinical trials are to be carried out within a network of leading European centers in gynaecologic oncology: EORTC/ENGOT or CCRN (cervical cancer research network. CCRN has been created within the International Gynecology Cancer Society by Prof Henry Kitchener from Manchester (UK) with the objective to have academic based trials originating from single centers and involving countries with lesser developed structures for screening and treatment of cervical cancer. 


Work performed and main results achieved

RAIDs started October 1st, 2012. Consortium members are from 7 European countries (France, Germany, the Netherlands, Serbia, Moldova, Romania and Hungary). The consortium voted the recent integration (October 2014) of a new clinical operations platform, HCTC from Hannover, as a partner with the mission to assist the coordination of the BioRAIDs trial in Germany, Moldova and Romania. The consortium is proceeding with registering an amendment of the DoW after receiving the greenlight from the European commission for an 18 months extension. The final consortium meeting will thereby be in March 2017.



  • Ethical and regulatory approval of the BioRAIDs (biobanking trial) is achieved in all countries and patient accrual is proceeding at an enhanced rate.

  • Quality control aspects
    Radiotherapy: Teaching and contouring sessions for radiotherapy have already been presented in conferences. Educational tools consisted in web based tumor contouring workshops with expert guidance. (Rivin del Campo et al. 2014 Quality input of an Online Delineation Workshop in Advanced Stage Cervical Cancer.).
    Samples: Quality control for tumor samples (% tumor cells in biopsy samples, sufficient DNA in serum samples, exome coverage, pathology review) were set up conjointly by ERASMUS, NKI and SeqOmics.

  • Imaging: Quality control for MRI imaging and review of complete response is in the process of being set up in Serbia; Prof. Dr. Katarina Koprivsek from IOV will be in charge of this task.


The phase I DNA vaccine (HPV targeted therapy) trial sponsored by NKI in the Netherlands completed patient inclusions and immunological analysis is in progress. The ethical and regulatory submissions are in preparation for phase 2.


SCIENTIFIC WORK achieved during the first 30 months

  • Exome sequencing of the first tumor samples has been processed at SeqOmics.

  • Exome sequencing and drug screening of 23 CC cell lines is finalized and analyses are ongoing. Correlations linking molecular alterations to sensibility/resistance to certain drugs or drug combinations are expected.

  • Bio informatics analysis are ongoing

  • Preclinical mouse models for tumor micro-environmental studies have been developed and are published in journals with a high impact factor. Early preclinical mouse data on combining vaccine and radiotherapy are published as already previously reported.

DISSEMINATION to the public and scientific communities
Dissemination actions have led to a better visibility of the RAIDs project on an international level and to the wider understanding of the need for targeted approaches in the field of cervical cancer.
Video clips explaining RAIDs have been produced (
A dropbox for patients requests for information in the field of precision medicine has been inserted on the RAIDs website as well as in the cervical cancer factsheet of ESGO. It allows patients to ask questions in relation to their treatment and to potential protocols regarding precision medicine in their native language. Clinicians from the RAIDs consortium will ensure feedback to patients (


Expected final results, potential impact and use

RAIDs aims to define a set of stratification criteria based on molecular profiling. Its results will give insight into dominant genomic and protein signalling pathway alterations, enabling the identification of prognostic and predictive biomarkers for standard or targeted therapy in CC.

Immunological data from trials involving vaccine +/- checkpoint inhibition will provide information on predisposing conditions for immune rejection or tolerance of this virally transmitted disease.

The RAIDs consortium aims

  • to provide a safer and more efficient therapy for the individual patient;
  • to raise awareness in countries with lesser screening practices;
  • to improve the quality of life for women with cancer via:

    • a) the acquisition of defined molecular data for better treatment decisions,
    • b) targeted pilot trials directed at specific alterations as well as targeted vaccine trials directed against the HPV
    • c) the continuous evaluation of standards of care by comparing standards and outcome in all the RAIDs centers

  • to disseminate information on innovative practices in concertation with the help of other international structures, be the clinical trial orientated [EORTC (European Oranisation for Research and Treatment of Cancer) and ENGOT (European Network for Gyneacological Oncology Trials)] centers or international societies such as [ESGO (European Society for Gynaecological Oncology), ESMO (European Society for Medical Oncology) and IGCS (International Gynaecological Cancer Society)].

  • to develop new tools and ideas on future treatments using drug combinations which may be exploited and create economic wealth.