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A Groundbreaking Stand-Alone Diagnostic Kit to Predict Human Papilloma Virus Infections Evolving into Cervical Cancer

Periodic Reporting for period 2 - HPV OncoPredict (A Groundbreaking Stand-Alone Diagnostic Kit to Predict Human Papilloma Virus Infections Evolving into Cervical Cancer)

Reporting period: 2019-09-01 to 2020-08-31

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 cervical 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.
Since project start, the consortium partners, GeneFirst and Hiantis, have collaborated well to conduct the project in accordance with the GA despite some of the challenges with administrative delays and the pandemic. Throughout the project we held regular meetings, teleconferences and email exchanges. We collaborated on product development, recruitment, subcontractors, clinical study progression, project reporting and market updates. We involved a coach with experience in developing IVDs, giving support to achieve a solid Marketing and Communication Strategy. We now seek coaching to support the next phase including regulatory guidance and commercial route to market. The development and analytical validation of the new HPV OncoPredict IVDs has been completed with the all deliverables submitted on time. Due to the need to submit an amendment request in July 2020 (subsequently approved on August 31st, 2020), the 24 month report was submitted at M26 as it coincided with the period report preparation. We have successfully achieved MS1 and MS3. Although software development milestone has not been completed, we have asked for an extension for this work to be completed by M36. This milestone will be achieved once clinical validation data are generated.

Project risks are regularly monitored and mitigation strategies deployed when appropriate. This is pertinent during these unpredictable times with the pandemic; we have a good grasp of the potential risks and delays and have been in regular communications with the PO to discuss concerns. We have experienced delays due to the administrative process involved in signing a contract with one of the centres providing the clinical samples, the stringent ethical approval involving GDPR and the pandemic lockdown situation which lasted 6 months, the effects of which are still present - these have been addressed in the amendment request.

The technical files have been compiled where assays have shown excellent performance. Inter-laboratory testing is currently underway; the results of which will contribute toward the clinical validation part of the CE requirement.

We realised that due to the nature of the assays, different software analyses are required. Two software developers with specific expertise in their respective area are to be utilised. Meanwhile, we are working on automating a complete end-to-end workflow for the assays. This ensures that the assays are easy to operate and that analyses are easy to interpret for users of all experience.

We attended EUROGIN 2019 and had the opportunity to disseminate project results to date with oral and poster presentations and a trade stand. It was also an opportunity to sit down with all participating centres for WP5, 6 and 7 to discuss progress, signing of contracts and ethical approvals. Unfortunately due to the national lockdowns implemented throughout most of Europe, all conferences were cancelled or suspended in the second half of this reporting period. Some of the planned work for the project were impacted, notably clinical validations. Hospitals had to re-allocate resources to COVID-19 related cases, and all patient appointments for HPV were suspended. However, we continues to work through this period by ensuring that all documentations were in place so that when normality resumed, validations can continue accordingly.

The protocol for the triage WP7 has been revised. The new protocol, “VALidation of tests usable as a first step TRIage to manage hrHPV positive women” (VALTRIHP) will encompass the use of fresh HPV samples as opposed to biobanked samples (a potential risk identified in Reporting Period 1). This requires access to primary HPV screening centres; we have identified these sites and are now working on the necessary administration and ethical approval for the study.

We have further defined the commercialisation plan and target markets. As more countries look to implement HPV screening programs, it creates new opportunities to engage with key opinion leaders and regulators on the adoption of HPV OncoPredict as part of the testing workflow. More importantly it creates opportunities for countries that have adopted screening and are now looking for a molecular triage method to assess disease progression. Consortium has been preparing for the transition of the regulatory pathway and the potential impact on product development and approval.
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.