DESCRIPTION (provided by applicant):HPV-associated cervical cancer is among the leading causes of death in women worldwide, with more 500,000 cases and 275,000 deaths annually. While repeated screening through frequent use of the Papanicolaou (Pap) smear has drastically reduced the incidence and mortality of cervical cancer in developed nations, the vast majority of cervical cancer-related deaths occur in low- and middle-income countries with minimal healthcare infrastructure. Cytology-based prevention programs have proven to be extremely difficult to implement and sustain in low-resource settings, and as a result over 85% of new cervical cancer cases originate in developing countries. The lack of adequate infrastructure for traditional cytology-based screening combined with the presentation of cervical cancer, where symptoms are not present until the cancer is in an advanced stage, emphasize the clinical need for a screening test appropriate for low resource settings. Development of a reliable Point-of-Care (POC) test with high sensitivity and specificity has the ability to reduce the incidence and mortality of cervical cancer worldwide. We propose to develop a novel nanotechnology- based diagnostic assay platform to detect cervical cancer progression in low-resource settings. This multiplex assay platform, which is currently being developed for non-oncology applications by Becton Dickinson (BD), is designed to be low-cost, easy to use, and inexpensive. We propose to adapt this platform to develop a highly specific diagnostic test that will screen women who do not need treatment and identify women with cervical lesions who need to be referred for colposcopy. The diagnostic test is based on Surfaced Enhanced Raman Scattering (SERS) technology, that enables detection of multiple targets in a complex sample without the need for washing or purification. The test and analysis is completed in less than 30 minutes, provides a "sample-in- answer-out" workflow, making the platform ideal for a "screen and treat" test in low-resource settings. Diagnostic development and validation will be done in close collaboration with a multidisciplinary team with expertise in HPV and cervical cancer screening as well as clinical oncology. By combining BD's experience in assay development, global healthcare delivery, and regulatory approval with the clinical expertise of other team members, the team has the expertise required to develop and validate a POC cervical cancer test for low resource settings. In addition to BD assay development, engineering, global healthcare delivery, and regulatory personnel, the team includes Dr. Jennifer S. Smith (UNC-Chapel Hill), Dr. Douglas Clark (UNM), Dr. Mark Stoler (UVA Health System), Dr. Scott McClelland (UW), and clinical validation site leaders including Dr. You-Lin Qiao (Chinese Academy of Medical Sciences), Dr. Nelly Mugo (Kenya Medical Research Institute), Dr. Jose Fregnani (Barretos Cancer Hospital), and Dr. Adhemar Longatto-Filho (Barretos Cancer Hospital, Brazil).

PUBLIC HEALTH RELEVANCE: We propose to develop a Point-of-Care diagnostic test for cervical cancer in low resource settings. The novel nanotechnology-based diagnostic is robust, portable, inexpensive, and offers a simplified workflow and rapid time-to-result. The proposed diagnostic test has the potential to significantly improve healthcare outcomes for women in low resource settings worldwide.