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NIH/NCI 473 - Point of Care Detection of Antibodies Against HPV16/18 E6 and E7 Oncoproteins in Oropharyngeal Cancer

Fast-Track proposals will be accepted.

Direct-to-Phase II proposals will NOT be accepted.

Number of anticipated awards: 2-4

Budget (total costs, per award):

Phase I: up to $400,000 for up to 12 months

Phase II: up to $2,250,000 for up to 2 years

PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.

Summary

The incidence of oropharyngeal cancer (OPC) is on the rise in many countries. A significant number of OPCs are caused by human papillomavirus (HPV) infections. Current prophylactic HPV vaccines can eventually prevent HPV-related cancers, as has been shown already for cervical cancer in young women. However, there are still several generations of people at risk of HPV-related OPC for whom prophylactic HPV vaccination will not be offered and would have limited or no benefit. Early detection could optimize effective intervention and treatment to reduce the deaths caused by HPV-related OPCs. Unfortunately, there is currently no recommended screening test or approach for the prevention or early detection of HPV-related OPC. Therefore, there is a significant unmet need to improve the early detection of HPV-related OPC for optimizing intervention and treatment.

HPV16 is the most important type in HPV-positive cancers, accounting for 90% of HPV-driven OPCs; HPV18 is the next most important type. HPV is a very common exposure, but most are benign and will become undetectable in a year or two. Thus, the detection of HPV DNA is sensitive, but not specific for HPV-related cancers. However, it is known that antibodies against HPV E proteins are strongly associated with and are highly specific for HPV-related OPC. Specifically, anti-HPV16 E6 and E7 antibodies can be detected years before HPV-related OPC becomes clinically detected. Detecting antibodies against HPV16 and 18 E6/E7 oncoproteins in high-risk individuals will facilitate increased surveillance, including imaging and biopsy, particularly for high-risk subjects, such as males, in regions with high cancer incidence, leading to the improvement of clinical guidelines and targeted interventions.

Project Goals

The goal of this topic is to support the development and validation of a rapid, point-of-care (POC) device for HPV-related OPCs; the device should be capable of separate detection of antibodies against HPV16 and HPV18 E6 and E7 oncoproteins. Since antibodies against HPV16 and HPV18 E6 and E7 proteins are strongly associated with developing or having HPV-related cancer, technologies that facilitate the detection of these antibodies may help detect HPV-related OPC early to optimize intervention and treatment, ultimately reducing deaths caused by HPV-related OPC.

This POC test might be used in a number of healthcare delivery settings: 1) by prescription (and sent by mail), 2) over the counter from a pharmacy, and 3) in the primary healthcare setting. The POC test must meet the following required specifications: 1) it can be used as a self-test in non-clinical settings, including at home, or in the primary care setting, 2) testing requires only the use of blood collected at home via finger prick (or saliva), and 3) achieves the same analytic performance as predicate tests, such as enzyme-linked immunosorbent assay (ELISA) tests and Luminex-like tests. echnologies used in lateral flow tests, such as those for COVID-19, might be adapted for this purpose. Other technologies, such as those based on microfluidics, might be amenable for this purpose. The prototype test also may include detection of antibodies against HPV33, 35, and 52 E6 and E7 proteins to increase the sensitivity for detection of HPV-related OPC and/or other highly clinically specific serological biomarkers for HPV-related cancers and HPV-unrelated OPC.

Phase I Activities and Deliverables

Offerors must propose to conduct activities that lead to the development of a working prototype point-of-care (POC) antiHPV16 and HPV18 E6 and E7 antibody test:

  • Applying user-centric design principles, develop prototype of POC device/test kit to detect antibodies against
  • HPV16/18 E6 and E7 oncoproteins from appropriate biospecimens.
    • Offerors should clearly specify where the device/test is intended for use (e.g. home, primary care setting, etc.), the intended population, and consider all elements of the testing kit, including but not limited to transport media, shipment kits, and method of biospecimen collection.
  • Conduct studies to establish analytical performance in the intended biospecimens (e.g. finger prick or saliva) for each marker (e.g., analytical sensitivity and specificity) and other performance characteristics (e.g., limit of detection, consistency, and reproducibility). Performance of POC device/test may use biospecimens spiked with HPV antibodies, for initial testing, but should also demonstrate detection of HPV antibodies from human specimens.
  • Demonstrate collaborations and establish partnerships with the place(s) where future clinical evaluation study will be conducted (Phase II of contract).
  • Provide letters from the collaboration organization(s) that can provide relevant patient access for future studies in the Phase I progress report in addition to those in the original proposal (Phase II of contract).

Phase II Activities and Deliverables

Offerors must propose activities leading to the manufacturing and regulatory approval of the test/kit, including but not limited to:

  • Conduct studies to evaluate and test user acceptability and feasibility in high-risk of populations (i.e., number of (oral) sexual partners, older men, etc.) as well as general population.
  • Conduct initial clinical testing with the prototype HPV16 and HPV18 E6 and E7 antibody test and compare results to a well-validated, standard serology (reference) test (e.g., ELISA or multiplex assay such as bead-based assays) for HPV16 and HPV18 E6 and E7 antibodies to determine the clinical performance measures (e.g., concordance with lab-based standard test, and clinical sensitivity and specificity).
  • Offerors should establish a collaboration or partnership with a research group or medical facility that can provide relevant patient access; offerors must provide a letter of support from the partnering organization(s) in the proposal.
  • Develop a regulatory strategy/plan that is necessary to file an appropriate regulatory application for the test.
  • Develop a well-defined sample collection and testing kit under good laboratory practices (GLP) and/or good manufacturing practices (GMP).
  • Perform manufacturing scale-up and production for multi-site evaluations.
  • Demonstrate the clinical sensitivity and specificity of the test by performing multi-site and multi-test evaluations.
  • Establish a strategy for FDA regulatory approval and insurance and/or CMS reimbursement.
  • Engage with FDA to refine and execute an appropriate regulatory strategy. If warranted, provide sufficient data to submit a regulatory application to obtain approval for clinical application.

 

Receipt date: Friday, October 18, 2024, 5:00 p.m. ET

Apply for this topic on the Contract Proposal Submission (eCPS) website.

View the full PHS2025-1 Contract Solicitation.

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