Development of an HPV-E6 Cervical Neoplasia Test for Use in Centralized Diagnosti

开发用于集中诊断的 HPV-E6 宫颈肿瘤检测

• 批准号: 8549172
• 负责人: Michael Paul Belmares
• 金额: $ 9.49万
• 依托单位: ARBOR VITA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-21 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8549172
• 关键词: Affect; Applications Grants; Attention; Automation; Biological Assay; Biological Markers; Biopsy; Cancer Etiology; Cancerous; Carcinogens; Cause of Death; Cells; Cellular Morphology; Centers for Disease Control and Prevention (U.S.); Cervical; Cessation of life; Clinic; Clinical; Clinical Research; Clinical Sensitivity; Colposcopy; Country; Detection; Developed Countries; Development; Diagnostic; Diagnostic tests; Direct Costs; Early Diagnosis; Epithelial Cells; Expenditure; Feasibility Studies; Future; Genes; Grant; HPV-High Risk; High Prevalence; Human Papilloma Virus Vaccine; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; Immunoassay; Individual; Intervention; Lead; Lesion; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Medical; Methods; Molecular; Molecular Diagnostic Testing; Monoclonal Antibodies; Neoplasms; Nucleic Acids; Oncogene Proteins; Outcome; Pap smear; Papillomavirus; Pathologist; Patients; Phase; Population; Predictive Value; Proteins; Recombinants; Research Design; Risk; Sampling; Sensitivity and Specificity; Severities; Severity of illness; Specificity; Specimen; Swab; Technology; Testing; Transcript; Translating; Validation; Viral; Visit; Visual; Woman; Women' s Health; arborvitae; base; cost; design; detector; effective therapy; follow-up; high throughput screening; meetings; mortality; prevent; product development; programs; prototype; public health relevance; response; screening; tumorigenesis

DESCRIPTION (provided by applicant): Cervical cancer is the leading cause of cancer-related death in women. It causes over 250,000 death world-wide / year, with 80% occurring in countries without systematic cervical neoplasia screening programs5. High risk Human Papillomavirus (HPV) infection is responsible for >99% of all the cervical cancers4. Early detection of HPV infection by the Pap Test has reduced the death toll in developed nations significantly10. Despite its merits, the Pap Test is no longer considered an adequate screening technology due to the high false-negative and false-positive rates as a result of subjective visual interpretation of cell morphology by pathologists7. In recent years, several nucleic acid-based HPV diagnostic tests have emerged8. These tests have excellent clinical sensitivity, but fail to provide the desired clinical specificity, due to the high prevalence of HPV infection without pathological outcome8. Consequently, utilization of molecular HPV tests for screening may lead to costly over-treatment of patients (follow-up visits; colposcopies; biopsies). In response to the need for a specific yet sensitive screening method, Arbor Vita Corporation proposes the development of a diagnostic test that detects the Papillomavirus protein E6, a pivotal oncoprotein in cervical oncogenesis. E6 oncoprotein levels in cervical swab specimens from patients with neoplasia correlate positively with the severity of lesions6. Accordingly, an HPV-E6 oncoprotein-based screening test has the potential to identify HPV-positive women who are at risk to develop cervical cancer amidst the much larger number of women with clinically irrelevant HPV infection. In this grant, the applicants propose the development of a high-throughput bead-based assay to detect and to type E6 oncoproteins from 15 high-risk HPV types for use in centralized clinical labs. The new HPV-E6 oncoprotein test will harness the technological advances in bead-based immunoassays and the availability of highly specific HPV-E6 monoclonal antibodies at Arbor Vita to achieve the desired high sensitivity, specificity and capability for automation. Under phase 1, our approach is focused on the development of the bead-based 15 HPV type E6 oncoprotein diagnostic prototype test. Upon successful completion of phase 1, the applicants will submit a phase 2 grant application for further product development towards the final format of the test that will be used in clinical studies for design validation.

描述（由申请人提供）：子宫颈癌是妇女癌症相关死亡的主要原因。全世界每年有超过25万人死于宫颈癌，其中80%发生在没有系统宫颈肿瘤筛查计划的国家。高风险的人乳头瘤病毒（HPV）感染导致了99%的宫颈癌。在发达国家，通过巴氏试验早期检测HPV感染大大减少了死亡人数。尽管巴氏试验有其优点，但由于主观视觉的高假阴性和假阳性率，巴氏试验已不再被认为是一种适当的筛查技术