Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - HPV OncoPredict (A Groundbreaking Stand-Alone Diagnostic Kit to Predict Human Papilloma Virus Infections Evolving into Cervical Cancer)

Teaser

Cervical cancer is the fourth most frequent cancer in women, estimated to kill 250,000 women annually. With the identification of the human papillomavirus (HPV) as the causative agent of essentially all cervical cancer cases, HPV molecular tests have been developed to allow...

Summary

Cervical cancer is the fourth most frequent cancer in women, estimated to kill 250,000 women annually. With the identification of the human papillomavirus (HPV) as the causative agent of essentially all cervical cancer cases, HPV molecular tests have been developed to allow screening for early disease detection. HPV is the most commonly acquired sexually transmitted virus, with around four out of five people contracting this infection at some point during their lifetime. Available HPV tests are unable to discriminate HPV infections regressing spontaneously from those turning into cancer. Screening refusal is also an important problem in several countries, resulting from social, economic and/or ethnic barriers, hindering cervical cancer prevention in these women. This, together with failure in many countries to implement gender-neutral HPV vaccination, has resulted in IARC’s projections showing that, unless innovative preventive measures are implemented, the burden is expected to increase to almost 460.000 deaths per year by 2040, an increase of nearly 50% over the number of deaths in 2018.
HPV OncoPredict is unique in its power to discriminate clinically relevant from irrelevant HPV infections by means of a high-throughput molecular reflex testing algorithm: 1) screening assay able to detect all oncogenic HPV infections, 2) triage assays for HPV positive samples comprising of two second line biomarkers as indicators of risk, normalized hrHPV viral load and viral-induced cellular oncogenic transcripts. This innovative diagnostic device will allow reliable testing on self-collected vaginal or urine samples, maximising screening uptake. HPV OncoPredict IVDs developed and validated as part of this project will help identify those women at true risk of developing cancer. Risk-stratification will prevent unnecessary costly and stressful investigations and overtreatment of women with clinically irrelevant infections. Moreover, HPV OncoPredict assays will be clinically validated to ensure reliable results on both clinician-collected and self-collected samples, representing an important public health achievement as recent studies have shown that self-sampling improves adhesion of “non-responders” to screening programs, contributing to improved prevention and costs reduction for the health system.

Work performed

In this period consortium constantly collaborated to conduct the project in accordance to the grant agreement, requiring only few amendments due to technical or unforeseen issues. Throughout the project the consortium held regular meetings (09/18;05/19) as well as teleconferences and email exchanges to discuss progress, issues and potential risks. The consortium closely collaborated on: product development, recruitment, document control, subcontractors, coaching, project reporting and HPV market updates. The consortium involved a coach with experience in developing IVDs, giving support to achieve a solid Marketing and Communication Strategy. The consortium is now seeking coaching to support the next phase of the project including regulatory guidance. With constant collaborative work, the consortium made good progress with development and analytical validation of the new HPV OncoPredict IVDs with the following Deliverables submitted on time: Customer Requirement Specification (Month 3); 6 Months Report (Month 6); Marketing and Communication Strategy (Month 11); Updated Commercialization Plan (Month 12); and a 12 Months Report (Month 12), detailing progress made to the relevant WPs during this time.

In December 2018 the consortium attended EUROGIN conference, an opportunity to disseminate the work undertaken and to network with KOLs, researchers and industry partners in the field of HPV and cervical cancer. It also provided an opportunity to interact with project’s subcontractors (M. Arbyn, Sciensano; K.Cuschieri, Univ. of Edinburgh; M. Poljak, Univ. of Slovenia; F. Bottari, European Institute of Oncology in Milan). During the meeting it became clear that the Slovenian Center would not be able to participate in the European VALHUDES Study (WP6). An alternative clinical center was sought through regular teleconferences and constant communications with all clinical subcontractors, eventually identifying Prof. John O’Leary, The Univ Hospital & Trinity College, Dublin. This resulted in delays to subcontracting agreement signatures with CIRM, the Clinical Research Organization involved in the study conduction, as well with submission of study protocol for ethical approval as all clinical sites had to be defined. The consortium also had to seek alternatives for WP3 software development as the named subcontractor could no longer deliver according to the project’s requirements. The consortium jointly held numerous calls and meetings with potential software subcontractors to satisfy three aspects: value for money; delivery against requirements and future development and potential partnership for successful commercialization.

During development of HPV OncoPredict oncogenic transcripts assays (WP2), preliminary testing showed that RNA detection is best performed on fresh samples. As WP7 was based on the use biobanked samples from the Scottish HPV Archive, this finding was discussed both internally and with M. Arbyn, subcontractor involved in defining WP7 study protocol. The outcome was that a new study protocol had to be designed involving “fresh” residual samples from HPV-based cervical screening programs. Hiantis experienced some delays in the recruitment of employees and laboratory services necessary for assay development and analytical verification. GeneFirst went through 2 rounds of assay design freeze for optimization purposes delaying slightly on development and analytical verification. The consortium was regularly updating the Project Officer on progress and requirements for changes due to technical or unforeseen issues. Amendments Request was approved by the EC, allowing the consortium to plan the next phase of the project.

For exploitation and dissemination, the consortium has been very active in attending conferences (ECCMID, 04/19) as well as external network and international meetings (ie. Public Hearing organized by the FDA Medical Devices Advisory Committee in 03/19 Washington, USA to discuss and make rec

Final results

EU guidelines advocate use of HPV primary screening. The predictive HPV OncoPredict algorithm, allowing combined HPV screening and triage testing, will allow risk-stratification of women with HPV infections, avoiding the need for the women to go to follow-up visits, reducing women anxiety and healthcare costs. The capacity to predict the true risk of developing cancer, even on self-collected samples, will increase women participation to screening, the interval between testing and reduce unnecessary invasive investigations. This value proposition is unique and powerful, and the consortium believes that it will have huge socio-economic and public health impacts in cancer prevention globally.

Website & more info

More info: https://www.genefirst.com/hpv-oncopredict.