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

Periodic Reporting for period 3 - HPV OncoPredict (A Groundbreaking Stand-Alone Diagnostic Kit to Predict Human Papilloma Virus Infections Evolving into Cervical Cancer)

Reporting period: 2020-09-01 to 2021-08-31

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 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. Due to the need to submit an amendment request in July 2021 (subsequently approved on August 31st, 2021), the 36 month report was submitted at M36 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 M44. 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 communicated to the PO to discuss concerns. Due to the impact of the pandemic, recruitment has proven challenging for WP6 and WP7. We have contingency plans in place to ensure that we continue to recruit the number of patients required to achieve the DoA as set out in the GA.

Inter-laboratory testing (as part of WP4) has been completed in this period. When the outcomes of the clinical validations are available, these results will be added to the technical files which have already been compiled for the assays.

For WP5, the clinical validation using VALGENT-2 study samples and protocol was completed and WP is on track for completion.

Two software developers with specific expertise in their respective area have been utilised (WP3). 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.

For WP7, 500 subjects have been enrolled in the study in this period, and we anticipate that the rate of recruitment will increase as restrictions are lifted and more screening units will be involved; patients’ enrolment and sample testing are expected to be completed by project end.

We attended EUROGIN 2021 and had the opportunity to disseminate project results to date with two oral presentations and a trade stand. As we continued to experience travel restrictions, we attended virtual conferences and disseminated results digitally whenever possible. We have been part of the panel session where the VALTRIPH protocol as part of WP7 was presented, along with preliminary data obtained so far in the project. We have been invited to attend EUROGIN 2022 to disseminate results from WP6.

With our coach, we have been working together to understand the HPV market in a more critical manner, including assessment of key competitors and defining our USPs to increase commercial success. We continue to engage with KOLs 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.
On November 17th 2020, the WHO launched a global strategy to accelerate the elimination of cervical cancer as a public health problem in the midst of the COVID-19 pandemic. With the easing of the restrictions and gradual return to normality, it is vital that organised cervical cancer screening is maintained and monitored in settings where it can be safety provided. During the pandemic, many organised programmes were stopped or were disrupted. This ultimately has an impact on cervical cancer burden in regions with comprehensive cervical cancer control programmes. Several studies conducted across Europe, US and Canada looking at the impact of the pandemic on screening have shown that relatively short-term screening disruptions can lead to clinically significant decrease in cervical precancer detection. The outcomes of HPV OncoPredict clinical studies involving the use of self-collection devices are, therefore, very important in the provision of alternative screening strategies to facilitate the transition to more effective guidelines in developing prevention systems that are resilient to future care disruptions. This self-sampling strategy will allow for expansion of the reach of screening to underserved populations that do not participate in screening. It can also provide a safe environment for women to collect samples at home, reducing patient-provider contact and risk of COVID-19 exposures. Further, it may help address the backlog of screening tests accumulated during the pandemic by expanding the reach of catch-up services.