Unraveling the Interplay: Microbiome, p16 Expression, High-Risk HPV Infection, and Clinical Outcomes in Penile Cancer Across Diverse Patient Cohorts with Varied Mortality and Incidence Profiles
About This Grant
The incidence and mortality rate of penile squamous cell carcinoma (PSCC) is significantly higher in Puerto Rico compared to the continental United States (US). Puerto Rican men have approximately a three-fold higher incidence rate than non-Hispanic white men in the continental US. Our proposal will compare molecular profiles across 350 primary tumors representing distinct geographic areas to study the spectrum of disease prevalence and discover the possible biological cause of this health disparity. High-risk human papillomavirus genotypes (HR-HPV) are implicated in the carcinogenesis of PSCC through the action of viral E6 and E7 oncoproteins. E6 disrupts the p53 tumor suppressor pathway, while E7 inhibits the retinoblastoma protein (Rb) pathway, leading to increased expression of the p16 protein. Due to the ease of detecting p16 overexpression by immunohistochemistry (IHC), it serves as a marker for HR-HPV infection in PSCC. The World Health Organization recently recommended that p16 status be reported as a “requirement” for PSCC pathology, as it is a recognized biomarker for HR-HPV infection. However, various studies show that the expected concordance between p16 expression and HR-HPV infection may not hold true in high-incidence populations. We suspect that these discrepancies in concordance within such populations could stem from variations in the intratumoral microbiome or DNA methylation patterns. We hypothesize that microbiome profiles and DNA methylation patterns reflect stable reservoirs of biomarkers that indicate how HR-HPV influences the development and progression of PSCC. Our proposal seeks to utilize these markers as prognostic indicators of outcomes in populations with high rates of HR-HPV/p16 discordance. We will evaluate: Aim 1a. HR-HPV subtype using the Roche Cobas system; Aim 1b. p16 expression by IHC; Aim 1c. DNA methylation using reduced representation bisulfite sequencing (RRBS) and Aim 1d. microbiome using 16S rRNA sequencing. We will determine how the overall diversity of the tumor microbiome affects prognosis and how specific microbes correlate with p16 expression, HR-HPV infection, and clinical characteristics such as tumor stage, histological subtype, nodal stage, cancer-specific survival, disease-free survival, and overall survival. Similar correlations will be determined with DNA methylation patterns and specific loci. We are specifically interested in how these correlations differ between geographic areas to identify biological factors associated with PSCC health disparities. Our proposal could significantly change the biomarker used for determining HR-HPV infection in PSCC and could find relevant biomarkers for overall prognosis of PSCC in high incidence regions of the world.
Grant Summary
Unraveling the Interplay: Microbiome, p16 Expression, High-Risk HPV Infection, and Clinical Outcomes in Penile Cancer Across Diverse Patient Cohorts with Varied Mortality and Incidence Profiles is a NCI - National Cancer Institute grant providing up to $427K for university, nonprofit, healthcare org. Applications are due 2028-07-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $427K
2028-07-31
- 1Confirm your organization is eligible for Unraveling the Interplay: Microbiome, p16 Expression, High-Risk HPV Infection, and Clinical Outcomes in Penile Cancer Across Diverse Patient Cohorts with Varied Mortality and Incidence Profiles from NCI - National Cancer Institute, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NCI - National Cancer Institute before the deadline.
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Unraveling the Interplay: Microbiome, p16 Expression, High-Risk HPV Infection, and Clinical Outcomes in Penile Cancer Across Diverse Patient Cohorts with Varied Mortality and Incidence Profiles: Frequently Asked Questions
Who is eligible for the Unraveling the Interplay: Microbiome, p16 Expression, High-Risk HPV Infection, and Clinical Outcomes in Penile Cancer Across Diverse Patient Cohorts with Varied Mortality and Incidence Profiles?
Unraveling the Interplay: Microbiome, p16 Expression, High-Risk HPV Infection, and Clinical Outcomes in Penile Cancer Across Diverse Patient Cohorts with Varied Mortality and Incidence Profiles is offered by NCI - National Cancer Institute and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Unraveling the Interplay: Microbiome, p16 Expression, High-Risk HPV Infection, and Clinical Outcomes in Penile Cancer Across Diverse Patient Cohorts with Varied Mortality and Incidence Profiles provide?
Unraveling the Interplay: Microbiome, p16 Expression, High-Risk HPV Infection, and Clinical Outcomes in Penile Cancer Across Diverse Patient Cohorts with Varied Mortality and Incidence Profiles provides up to $427K per award from NCI - National Cancer Institute. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Unraveling the Interplay: Microbiome, p16 Expression, High-Risk HPV Infection, and Clinical Outcomes in Penile Cancer Across Diverse Patient Cohorts with Varied Mortality and Incidence Profiles deadline?
Applications for Unraveling the Interplay: Microbiome, p16 Expression, High-Risk HPV Infection, and Clinical Outcomes in Penile Cancer Across Diverse Patient Cohorts with Varied Mortality and Incidence Profiles are due 2028-07-31 (open). Because deadlines can change, verify the date with the funder, NCI - National Cancer Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Unraveling the Interplay: Microbiome, p16 Expression, High-Risk HPV Infection, and Clinical Outcomes in Penile Cancer Across Diverse Patient Cohorts with Varied Mortality and Incidence Profiles?
To apply for Unraveling the Interplay: Microbiome, p16 Expression, High-Risk HPV Infection, and Clinical Outcomes in Penile Cancer Across Diverse Patient Cohorts with Varied Mortality and Incidence Profiles, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NCI - National Cancer Institute.