Transcriptomic, Proteomic, and Genomic Mutational Fraction Differences Based on HPV Status Observed in Patient-Derived Xenograft Models of Penile Squamous Cell Carcinoma.

Metastatic penile squamous cell carcinoma (PSCC) has only a 50% response rate to first-line combination chemotherapies and there are currently no targeted-therapy approaches. Therefore, we have an urgent need in advanced-PSCC treatment to find novel therapies. Approximately half of all PSCC cases are positive for high-risk human papillomavirus (HR-HPV). Our objective was to generate HPV-positive (HPV+) and HPV-negative (HPV-) patient-derived xenograft (PDX) models and to determine the biological differences between HPV+ and HPV- disease. We generated four HPV+ and three HPV- PSCC PDX animal models by directly implanting resected patient tumor tissue into immunocompromised mice. PDX tumor tissue was found to be similar to patient tumor tissue (donor tissue) by histology and short tandem repeat fingerprinting. DNA mutations were mostly preserved in PDX tissues and similar APOBEC (apolipoprotein B mRNA editing catalytic polypeptide) mutational fractions in donor tissue and PDX tissues were noted. A higher APOBEC mutational fraction was found in HPV+ versus HPV- PDX tissues (p = 0.044), and significant transcriptomic and proteomic expression differences based on HPV status included p16 (CDKN2A), RRM2, and CDC25C. These models will allow for the direct testing of targeted therapies in PSCC and determine their response in correlation to HPV status.

Using Implementation Mapping to increase uptake and use of Salud en Mis Manos: A breast and cervical cancer screening and HPV vaccination intervention for Latinas.

Background: Despite CDC recommendations for breast and cervical cancer screening and HPV vaccination, cancer control behaviors are underutilized among low-income Latinas. Salud en Mis Manos (SEMM), adapted from Cultivando La Salud, is a community health worker- (CHW-) delivered evidence-based intervention (EBI), shown to increase breast and cervical cancer screening. Methods: We used Implementation Mapping to create SEMM-Dissemination and Implementation Assistance (SEMM-DIA), a set of implementation strategies designed to support implementation and maintenance of SEMM in clinic settings. Specifically, we used Implementation Mapping's five iterative tasks to guide the use of theories and frameworks, evidence, new data, and stakeholder input to develop strategies to accelerate and improve implementation fidelity, reach, and maintenance of the SEMM intervention. The resulting implementation mapping logic model also guides the SEMM-DIA evaluation plan to assess reach, effectiveness, implementation, and maintenance. Discussion: Increased use of implementation planning frameworks is necessary to accelerate the translation of EBIs to public health practice. This work demonstrates the application of Implementation Mapping to develop SEMM-DIA, providing a model for the development of other implementation strategies to support translation of evidence-based health promotion interventions into clinic settings.

Prognostic Significance of p16 and Its Relationship with Human Papillomavirus Status in Patients with Penile Squamous Cell Carcinoma: Results of 5 Years Follow-Up.

Penile Squamous Cell Carcinoma (PSCC) is associated with high-risk human papillomavirus (HR-HPV). The immunohistochemical (IHC) test for p16INK4a (p16) is highly correlated with HR-HPV expression in other SCCs. To investigate whether the expression of p16 IHC or HR-HPV is associated with survival in PSCC, we conducted a single institution analysis of 143 patients with a diagnosis of PSCC and, available tissue were tested for p16 IHC staining patterns, histological subtype, tumor grade, and lymphovascular invasion (LVI) by an experienced pathologist. HR-HPV status using the Cobas PCR Assay or the RNAScope high-risk HPV in situ hybridization kit were also assessed. Patient characteristics were summarized using descriptive statistics of clinico-pathologic variables. Kaplan-Meier was used to estimate median overall survival (OS), cancer specific survival (CSS) and correlated with HPV, p16, and other study variables. Patients with p16+ tumors had a significantly longer median CSS in comparison to the p16- group (p = 0.004), with respective 5-year CSS probability of 88% (95% CI; 0.84, 1) versus 58% (95% CI; 0.55, 0.76; p = 0.004). HPV status did not predict survival outcomes. Multivariable analysis with respect to OS and CSS, showed that p16+ status was associated with a lower risk of death (HR = 0.36, 95%CI; 0.20-0.67, p = 0.001), and improved CSS (HR = 0.20, 95% CI; 0.07-0.54, p = 0.002) after adjusting for covariates. In conclusion, tumor p16 status via IHC was an easy to perform independent prognostic factor for OS and CSS that correlates with HR-HPV expression.