Browsing by Subject "Papillomavirus Infections"
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Item Anal Cancer Screening in a High-Risk Population: A Quality Improvement Initiative(2019-03-29) Bieterman, Andrew; Reed, W. Gary; Anandam, Joselin; Lau, Abby; Quinn, AndrewBACKGROUND: The main risk factor for the development of anal cancer is acquisition of the human papilloma virus (HPV). Individuals infected with the human immunodeficiency virus (HIV) have a higher prevalence of HPV and subsequently developing HPV induced dysplasia. The incidence of anal cancer among HIV positive men who have sex with men (MSM) has been estimated to be approximately twice that of HIV negative MSM with rates as high as 112-144 per 100,000. By relying on similarities between the anus and the cervix, and the established success of cervical cytology screening in reducing the incidence of cervical cancer, anal cancer screening programs have been established to identify pre-cancerous lesions. LOCAL PROBLEM: A retrospective chart review of anal cancer incidence at Parkland Hospital revealed a significant burden of anal cancer amongst HIV positive patients. As such, Parkland has decided to implement a policy of annual anal cancer screening among all HIV patients via anal cytology screening and referrals to proctology for any abnormal anal cytology samples. METHODS: In order to assess the monthly anal cancer screening rate, we looked at the absolute number of anal cytology samples performed in a 28 day period. The list of anal cytology samples performed was pulled from the Cerner laboratory information system (LIS) and correlated with a quarterly chart review using the electronic medical record (EMR). Utilizing, QI MACROS in EXCEL, we were able to create a run chart to identify trends in anal cancer screening rates over the duration of the project. We used chi-squared test of independence and unpaired t-test to determine statistical significance. INTERVENTIONS: We implemented a multi-step process involving over 10 Plan-Do-Study Act (PDSA) cycles for increasing the number of anal cytology samples performed in the clinic. The three most impactful PDSA cycles are discussed in the article. RESULTS: The primary outcome of monthly anal cancer screening rate increased over the duration of the project from an average of 19.5 in 2015 to 58.6 samples collected per month in 2018, a 199.3% increase relative to baseline (p < 0.001). While the interventions implemented were successful in increasing anal cancer screening rates, we were unable to determine which of the PDSA intervention cycles had the biggest impact on altering the clinic practice. Over the duration of the project, we screened 1908 patients. Of the patients screened, we identified 249 patients with abnormal anoscopy findings. Amongst the patients that had anal lesions on anoscopy, 10 developed anal cancer, 4.0%. When taking a closer look at these individuals and the electronic medical record, 3 patients were found to be completely asymptomatic at the most recent clinic prior to collection of the anal pap and would not have been referred to proctology if it weren't for the screening test, which ultimately resulted in an earlier diagnosis CONCLUSION: We were successful in taking previously proven interventions for increasing cervical cancer and adapting them for anal cancer. By increasing awareness to both patients and providers on the risks of anal cancer, instructing providers on the methods to screen for the disease, and providing timely feedback, we were able to increase the anal cancer screening rate in this large urban clinic with limited resources.Item The Art of Viral Oncogenesis: Lessons from Human Papillomavirus and Polyomavirus Transformed Cancers(2020-05-01T05:00:00.000Z) Zhao, Jiawei; Xu, Jian; Banaszynski, Laura; Pfeiffer, Julie K.; Wang, RichardViruses account for about 15% of all human cancer. Understanding viral oncogenesis can substantially broaden our general knowledge on the molecular mechanisms of carcinogenesis. In this dissertation, I focused on two types of DNA oncoviruses, human papillomavirus (HPV) and polyomavirus (HPyV), and identified novel mechanisms by which these two types of viruses cause human cancers. In HPV transformed cancer cells, I identified a novel circular RNA species, circE7, that spans and encodes the HPV E7 oncoprotein. I later demonstrated that circE7 translated E7 protein accounts for a substantial proportion of the E7 protein in a HPV transformed cancer cell line, and whose absence significantly impacts cancer cell proliferation in vitro and in vivo. In Merkel Cell Polyomavirus (MCPyV) transformed MCC cancer cells, I identified the activation of non-canonical NF-κB pathway activation by the MCPyV small T (ST) oncoprotein. I further demonstrated that the ectopically activated non-canonical NF-κB pathway is required for cell growth in low serum. The inhibition of non-canonical NF-κB signaling by a small peptide inhibitor also resulted in impaired cell growth in vitro and in vivo due to ER stress mediated apoptosis, suggesting a novel therapeutic intervention strategy for viral positive MCC (VP-CC) patients.Item Assessment of Circularized HPV16 E7 RNA, GLUT1, and PD-L1 in Anal Squamous Cell Carcinoma(2020-05-01T05:00:00.000Z) Chamseddin, Bahir Hassan; Wang, Richard; Le, Lu Q.; Hammer, SuntreaBACKGROUND: Anal squamous cell carcinoma (ASCC) is a rare, deadly malignancy caused by high-risk human papillomaviruses in up to 90% of cases and continues to be treated by cytotoxic therapy established 40 years ago. There is a dearth of reliable biomarkers for ASCC. The prognostic implication of programmed death-ligand 1 (PD-L1) expression remains controversial while other biomarkers, like glucose-1-transporter (GLUT1) expression levels, have not been examined in the setting of ASCC. More recently, covalently closed circular RNAs has been (circRNA) expression has been shown to be widespread in cancers, and circRNAs have been proposed to be potential biomarkers. In previous studies, we discovered a novel circular E7 RNA expressed by HPV16 (circE7), which has not been assessed as a potential biomarker in any diseases. OBJECTIVE: We hypothesize that human papillomavirus infection status, increased GLUT-1 expression, increased PD-L1 expression, and HPV E7 RNA expression will serve as biomarkers for higher mortality in patients with anal squamous cell carcinoma. METHODS: A retrospective, translational case series was conducted on twenty-two subjects to analyze PD-L1, GLUT1, HPV-ISH, and HPV circE7 in relation to the clinical features and overall survival of patients with anal squamous cell carcinoma. To supplement understanding of the HPV circE7 biomarker, bioinformatic analyses of RNA-Seq data from the Cancer Genome Atlas was performed on 875 subjects with HPV-driven head and neck cancer and cervical cancer. RESULTS: Improved overall survival could be predicted histologically by pure basaloid architecture (p=0.013), PD-L1 expression (p=0.08), HPV-ISH positivity (p<0.001), but not GLUT1 expression. Quantitative RT-PCR of archived tumors revealed that high levels of circE7 in ASCC were predictive of improved overall survival (p=0.023). Bioinformatic analyses suggested that the presence of high amounts of circE7 correlated to improved survival in 875 subjects (p=0.074). CONCLUSION: Glut-1 overexpression was ubiquitous among all anal squamous cell carcinoma cases but was not predictive of survival. This study adds to the growing evidence of PD-L1 expression correlation to improved survival in ASCC. CircE7 levels correlate with improved survival in anal squamous cell carcinoma but larger, prospective studies are necessary to confirm the potential role of circE7 as a biomarker.Item Microbial oncogenesis(1985-03-14) Mackowiak, Philip A.Item The role of human papillomaviruses in the generation of genital cancer(1993-08-12) Gaynor, Richard B.