Periodic Reporting for period 4 - HPV OncoPredict (A Groundbreaking Stand-Alone Diagnostic Kit to Predict Human Papilloma Virus Infections Evolving into Cervical Cancer) Période du rapport: 2021-09-01 au 2022-04-30 Résumé du contexte et des objectifs généraux du projet 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. Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent Since project start the consortium partners have collaborated well to conduct the project in accordance with the GA despite challenges with administrative delays and the impact of 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. 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 communicated to the PO to discuss concerns. Due to the impact of the pandemic, recruitment has proven challenging for WP7. We have communicated to the PO that we will continue with WP7 beyond project end with the aim to deliver results in the 12-month period. Overview of results1. All assays have completed CE marking and have the relevant technical documentations as required (WP2)2. Completion of inter- and intra- laboratory testing and results added to technical documentations (WP2 & WP4)3. The assays have been fully automated on high-throughput robotic platform (WP2)4. Software packages have been delivered according to specification (WP3)5. We have a complete end-to-end workflow for HPV testing incorporating 2, 3 and 4 above. 6. Completion of the VALGENT-2 study (WP5)7. Completion of the EU-VALHUDES study (WP6)8. Completion of recruitment for WP7 by October/November 2022. The subcontractor will make a core report by November 2022 and a full statistical report by January 2023. Final complete triage clinical assessment at 12 months for the HPV-positive women enrolled at screening will be available by Autumn 2023, whereby a core report is expected to become available by November 2023 9. Published and peer-reviewed article “Human papillomavirus (HPV) detection in vaginal self-samples: evaluation of eNat® as an alternative suspension medium to ThinPrep®PreservCyt® for vaginal swabs” in Open Research EuropeDissemination & exploitation1. Talks at EUROGIN 2022 include "European VALHUDES Findings” (WP6), “Validation of tests for the triage of HPV+ve women” (WP7), “Clinical validation of HPV OncoPredict® SCR and QT assays using the Valgent-2 framework” (WP5), Validation of the HPV OncoPredict assay on self-collected vaginal and urine samples: preliminary Italian data of the EU-VALHUDES study" (WP6)2. Poster presentations include “Evaluation of the clinical performance of HPV OncoPredict® QT assay within the VALGENT-2 framework” (WP5) at The British Society for Colposcopy and Cervical Pathology Annual Conference held in Belfast (May 2022). 3. ECCMID 2022 oral presentation “High-risk Human Papillomavirus (hrHPV) genotype-specific viral load in women with persistent infection”4. Acceptance of talk “High-risk HPV genotyping and viral load assessment for the management of HPV-positive women” at European Society of Clinical Virology (ESCV) Congress 20225. Results of HPV OncoPredict Screening (SCR) and Viral Load (QT) have been presented at Society of Italian Virology (SIV) with oral presentation “Self-collection for HPV screening: new approaches for the prevention of cervical cancer”) and at the Society of Italian Microbiology (SIM), oral presentation “Evaluation of HPV genotype-specific viral loads in clinician-collected cervical samples as compared to vaginal self-collected samples in women with cervical dysplasia.”6. High levels of engagement with the assigned Coach who has been instrumental is supporting the consortium with defining the market and the competition and the business strategy. 7. Engagement with KOLs and regulators on the adoption of HPV OncoPredict as part of the testing workflow8. Transition of products into the IVDR pathway Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent) The overarching aim of this project is to create an improved screening pathway for women at risk of developing cervical cancer. In this project we have put together an algorithm which allows us to successfully differentiate between a common asymptomatic infection and a clinically relevant cancer-producing disease, meaning that we identify those cases of HPV infection that ultimately lead to cervical cancer. The manner in which we do this is via the provision of highly sensitive first line screening test to capture those women that are HPV positive, as well as second line triage tests to further stratify the women in terms of their risk of developing cancers. Therefore, the project impact as stated in Section 2.1 of the DoA is still highly relevant, and in the last reporting period we explain in more detail how the pandemic has accelerated the importance of HPV screening in the context of building resilience in the healthcare systems and networks.