Thesis (doctoral)--München, 1935.

Thesis (doctoral)--München, 1935.

No description available.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / The role of viruses in most common cancers is undoubtedly important, yet highly underestimated. Human Papilloma Virus (HPV) has been implicated with 99.7% of cervical cancers and its oncogenic mechanism has been clearly identified. The association of cervical cancer with 90% of triple negative breast cancer (TNBC) cases in African countries creates an intriguing possibility of HPV being a candidate oncovirus for breast cancer. In fact, numerous recent tissue studies conducted throughout the world detected HPV DNA in breast cancer tissues of patients with cervical cancer, while high‐risk HPV types (16, 18, 33) were present in invasive ductal carcinomas. 5,6 Prevalence of HPV varied from 4% in Mexican to 86% in American women. The virus was noted to be present in tumor tissue only, with the exception of one study, which identified lower concentration of HPV in normal tissue. 7 Although substantial evidence exists supporting involvement of HPV in breast cancer, no clinical studies have been conducted to elucidate this relationship. The goal of our retrospective chart review was to examine the association of breast cancer and HPV‐related cervical dysplasia in a cohort of women in urban setting. 15% (39/260) had abnormal Pap‐smear, while 8% (16/198) were HPVpositive. No statistically significant difference of Pap‐smear abnormality or of HPV positivity were detected among the groups in all categories. However, we noticed that non‐luminal breast cancers, double negative and triple negative (DN and TN), have higher rate of HPV positivity: 13.3% non‐luminal vs. 6.3% of luminal breast cancers, 12.5% DN breast cancers and 11.5% of TN vs. 6.4% of luminal A and 6.3% of luminal B. This creates an intriguing possibility that HPV might be associated with more than 50% increase of incidence rates of non‐luminal breast cancers, suggesting a need for larger scale studies to confirm this association.

Introduction: Sinonasal inverted papilloma (SNIP) is an uncommon benign tumor with a high recurrence rate, significant malignant potential and unknown etiology. The population in Hong Kong is unique in its high population density and having a majority of Chinese people who are ethnically and geographically predisposed to certain cancers. Research on the etiology, pathogenesis, diagnosis and treatment of the neoplasm and comparison with reported findings from other parts of the world may contribute to management of the condition in terms of prevention, staging and treatment. / Aims: The aim of the thesis is to describe the common and unique clinico-pathological characteristics of SNIP in Hong Kong and compare these with reported characteristics in populations from other geographical areas and in other races with the expectation of attaining new insights into the diagnosis and management of SNIP in Hong Kong patients. / Methods: Four studies designed to evaluate the risk factors, viral associations, cell-cycle protein expression, radiological features, clinical features, treatment approaches and treatment outcomes were conducted. The findings of these studies were compared with those reported from different geographical areas of the world. Study 1: Evaluation of the risk factors associated with SNIP by a case-controlled epidemiological study of 50 patients with SNIP and 150 matched control patients. Study 2: Evaluation of the prevalence of human papillomavirus (HPV), Epstein-Barr virus (EBV), p21 and p53 expression in SNIP and comparison with reports from the literature. In a case-control study, 73 SNIP, 48 nasal polyps (NP) and 85 hypertrophied turbinates (HT) specimens were examined by polymerase chain reaction (PCR) for HPV. Seventy-three SNIP, 30 NP and 32 HT specimens were examined by in-situ hybridization (ISH) for EBV and by immunohistochemistry (IHC) for p21 and p53. SNIP results were compared with those of NP and HT (as controls). Study 3: Evaluation of the radiological signs, accuracy of prediction of tumor origin and extent, and accuracy of preoperative staging of SNIP of plain computed tomography by an observational study of plain CT scans and operative findings from 30 patients with SNIP. Study 4: Evaluation of the clinico-pathological features and treatment outcomes of SNIP in 56 patients seen between 1990 and 2008 with follow-up of more than 2 years and comparison with the results of the literature. / Results and conclusions: There are certain unique clinico-pathological features of sinonasal inverted papilloma (SNIP) in Hong Kong which are related to its predominantly Chinese population, high population density, heavy pollution and, accessible and efficient specialist services. Concordant with the results of another case-control study in the literature, the study described herein demonstrated that occupational chemical exposure, but not smoking, is a risk factor for SNIP. This is the first case-control study demonstrating that alcohol intake, allergic rhinitis, nasal polyposis, sinusitis, non-sinonasal papilloma and non-sinonasal malignancy are not risk factors for SNIP. The low prevalence of HPV in non-malignant sinonasal inverted papillomas (NMIPs) in Hong Kong suggests that it does not play a significant pathogenic role. The absence of EBV in SNIPs in Hong Kong concurs with most reports that EBV is not a causative agent. The high p21 and low p53 expression in SNIPs compared with the average values reported from other studies further support the presence of a non-p53-dependent p21 regulatory pathway. The higher prevalence of both HPV and p53 in malignant sinonasal inverted papilloma (MIP) than in NMIP agrees with other reports that both could be markers of malignant transformation. However, their inverse relation suggests they are independent factors. Although most plain CT signs are the same as those previously reported and not pathognomonic for SNIP, the high predictive value of the “pedunculation sign and absence of intra-tumor calcification are unique to Hong Kong patients. Concordant with other reports, “bony strut or focal hyperostosis is highly accurate in predicting the site of SNIP origin. This is the first report on the accuracy of preoperative CT staging, which is slightly lower than that of preoperative MRI staging (80% versus 86%). The estimated incidence of SNIP (2.4/1,000,000/year) is low but may be an underestimation as the number from the private sector is undetermined. The male:female ratio of SNIP patients in both Hong Kong and Asia is low, suggesting a geographic or racial influence on sex predilection. The absence of extrasinonasal extension, low rates of cellular atypia, dysplasia and synchronous malignancy in the Hong Kong SNIPs may reflect less aggressive tumor behavior as well as accessibility to efficient specialist services. The distribution of tumor origins, presenting symptoms and presenting stages of the Hong Kong SNIPs are similar to those reported elsewhere. The higher recurrence rate in the Hong Kong series is related to inadequate treatment of the tumor origin and inadequate conversion to combined external approaches in the early cases. Contrary to previously reported statistics, combined extranasal approaches were used more often in secondary cases than in primary cases. As in previously reported series, the recurrence rate in secondary cases tended to be higher than that in primary cases. Concordant with previous reports from the endoscopic era, most recurrences in Hong Kong occurred at the original tumor site and were discovered within the first 2 years after surgery. The average time of diagnosis of the first recurrence was much shorter than that of the pre-endoscopic era (1.2 years vs. 4.3 years). As reported elsewhere, about one-third of recurrences required combined external approaches for salvage. This is the first report comparing 2-, 5- and 10-year-follow-up results, and suggesting a minimum of 2 years’ follow-up before reporting results to avoid underestimation of recurrences. / Sham, Cheuk-lun. / Thesis (M.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 215-237). / CHAPTER 1 / Introduction / Chapter 1.1 --- Sinonasal inverted papilloma --- p.1 / Chapter 1.1.1 --- Nomenclature and classification --- p.1 / Chapter 1.1.2 --- Etiology and pathogenesis --- p.4 / Chapter 1.1.3 --- Gross and histological pathology --- p.9 / Chapter 1.1.4 --- Site of tumor attachment and extension --- p.10 / Chapter 1.1.5 --- Association with malignancy --- p.11 / Chapter 1.1.6 --- Incidence and demographics --- p.11 / Chapter 1.1.7 --- Clinical features --- p.12 / Chapter 1.1.8 --- Radiological features --- p.13 / Chapter 1.1.9 --- Staging --- p.14 / Chapter 1.1.10 --- Treatment modalities --- p.16 / Chapter 1.1.11 --- Treatment outcomes, recurrence and residual disease --- p.17 / Chapter 1.2 --- Unique characteristics of the Hong Kong population --- p.19 / Chapter 1.3 --- Research aims, areas and hypotheses --- p.22 / Chapter 1.3.1 --- Research aims --- p.22 / Chapter 1.3.2 --- Research areas and hypotheses --- p.23 / Chapter 1.4 --- Research plan and methodology --- p.25 / Chapter 1.5 --- Summary of Chapter 1 --- p.28 / CHAPTER 2 / Risk factors associated with SNIP / Chapter 2.1 --- Background --- p.29 / Chapter 2.2 --- Hypothesis --- p.29 / Chapter 2.3 --- Patients and methods --- p.30 / Chapter 2.4 --- Results --- p.35 / Chapter 2.5 --- Discussion --- p.39 / Chapter 2.6 --- Summary of Chapter 2 --- p.45 / CHAPTER 3 / Evaluation of the prevalence of HPV, EBV, p21 and p53 expression in SNIP in Hong Kong and comparison with results reported in the literature / Chapter 3.1 --- Background --- p.46 / Chapter 3.2 --- Hypothesis --- p.48 / Chapter 3.3 --- Patients and methods --- p.48 / Chapter 3.4 --- Results --- p.55 / Chapter 3.4.1 --- Overall results --- p.55 / Chapter 3.4.2 --- Comparison of the results of HPV studies --- p.57 / Chapter 3.4.3 --- Comparison of the results of EBV studies --- p.68 / Chapter 3.4.4 --- Comparison of the results of p21 studies --- p.71 / Chapter 3.4.5 --- Comparison of the results of p53 studies --- p.74 / Chapter 3.5 --- Discussion --- p.79 / Chapter 3.5.1 --- HPV and SNIP --- p.79 / Chapter 3.5.2 --- EBV and SNIP --- p.95 / Chapter 3.5.3 --- p21 and SNIP --- p.98 / Chapter 3.5.4 --- p53 and SNIP --- p.103 / Chapter 3.6 --- Summary of Chapter 3 --- p.115 / CHAPTER 4 / Evaluation of the radiological signs, accuracy of prediction of tumor origin and extent, and accuracy of preoperative staging of SNIP by plain computed tomography / Chapter 4.1 --- Background --- p.117 / Chapter 4.2 --- Hypothesis --- p.118 / Chapter 4.3 --- Patients and methods --- p.118 / Chapter 4.4 --- Results --- p.120 / Chapter 4.5 --- Discussion --- p.135 / Chapter 4.6 --- Summary of Chapter 4 --- p.142 / CHAPTER 5 / Evaluation of the clinico-pathological features and treatment outcomes of SNIP and comparison with results reported in the literature / Chapter 5.1 --- Background --- p.143 / Chapter 5.2 --- Hypothesis --- p.144 / Chapter 5.3 --- Patients and methods --- p.144 / Chapter 5.4 --- Results --- p.148 / Chapter 5.4.1 --- Incidence --- p.148 / Chapter 5.4.2 --- Demographics --- p.150 / Chapter 5.4.3 --- Presenting symptoms --- p.154 / Chapter 5.4.4 --- Site of tumor origin --- p.156 / Chapter 5.4.5 --- Rate of association with malignancy --- p.158 / Chapter 5.4.6 --- Staging of disease (Krouse system) and recurrence rate --- p.163 / Chapter 5.4.7 --- Treatment approaches and recurrence rates --- p.165 / Chapter 5.4.8 --- Comparison between patients with and without previous surgery --- p.167 / Chapter 5.4.9 --- Time and site of recurrence --- p.170 / Chapter 5.4.10 --- Surgical approaches used in salvage surgery --- p.175 / Chapter 5.4.11 --- Complication rate --- p.176 / Chapter 5.5 --- Discussion --- p.178 / Chapter 5.5.1 --- Incidence --- p.178 / Chapter 5.5.2 --- Demographics --- p.179 / Chapter 5.5.3 --- Present symptoms and duration --- p.180 / Chapter 5.5.4 --- Sites of tumor origin --- p.181 / Chapter 5.5.5 --- Association with malignancy --- p.182 / Chapter 5.5.6 --- Disease stages (Krouse system) and recurrence rate --- p.184 / Chapter 5.5.7 --- Treatment approaches and recurrence rates --- p.186 / Chapter 5.5.8 --- Comparison between patients with and without previous surgery --- p.187 / Chapter 5.5.9 --- Time and site of recurrence --- p.189 / Chapter 5.5.10 --- Surgical approaches used in salvage surgery --- p.191 / Chapter 5.5.11 --- Complication rate --- p.192 / Chapter 5.5.12 --- Management principles based on clinico-pathological features --- p.193 / Chapter 5.6 --- Summary of Chapter 5 --- p.197 / CHAPTER 6 / Summary of thesis and future perspective --- p.201 / REFERENCES --- p.215 / APPENDIX / Questionnaire for study of risk factors of SNIP --- p.238

Thesis (M.Sc. Med.) (Epidemiology and Biostatistics))--University of the Witwatersrand, Faculty of Health Sciences, 2014. / Introduction Ano-genital warts affect at least 30 million people worldwide. Ano-genital warts are caused by low risk Human Papilloma virus infections in 90% of cases. In African populations the ano-genital warts have not been adequately investigated thus our main goal was to highlight the factors associated with the occurrence of ano-genital warts among HIV infected individuals. Studies in both men and women have shown that the likelihood of getting anogenital warts is significantly increased when one is infected with HIV hence the need to investigate in this population. More over data suggests that HPV infection occur more frequently among HIV infected individuals because of the HIV associated CD4+ T-cell immune-suppression. Methods We conducted an analytical cross sectional study of routinely collected secondary medical data from Ward 21 ART clinic at the Hillbrow community centre in Hillbrow Johannesburg central. Our study participants were all HIV infected patients 16 years and older who attended the ART clinic between 01 January 2009 and 31 December 2011 and were recorded in the therapy edge database. Our outcome was clinically diagnosed ano-genital warts. We analysed data using the Chi squared test or Fischers exact test to make comparisons in bivariate analysis. Logistic regression was used to assess factors associated with ano-genital warts. Factors assessed were other STIs namely syphilis, herpes simplex virus type 2 and scabies as well as age, gender, first CD4 and employment status and ART status of a patient. The Models were assessed using the linktest and the Hosmer Lemeshow goodness of fit test. Results Ano-genital warts (AGWs) prevalence was 4% (251 out of 6634) among females and 3% (118 out 4116) among males. Prevalence of AGWs in both females and males decreased with increasing age. In females the prevalence was between 1% and 8% and in males it was between 1% and 4%. The odds of having ano-genital warts among females if one was above 25 years ranged from 1.6 to 18.3, showing an upward trend. Among females a CD4 count of less than 200 cells/ml3 was also associated with ano-genital warts occurrence, OR 1.32(1.02 - 1.72). Among males the odds of having ano-genital warts if one was not on ART were 1.53 (1.01 – 2.31) times when compared to those who were on ART. Discussion and Conclusion Prevalence of genital warts was highest among the younger age groups in both males and females and it decreased with increasing age consistent with literature. Age was strongly associated with ano-genital warts and the association became stronger with increasing age among females while no association was found among males. In line with findings from other studies we found low CD4 count of ≤ 200 cells/m3 to be associated with ano-genital warts in HIV positive females; however it was a weak association. Among males a weak association between ART status and ano-genital warts was established and none in females. This is consistent with the fact that in the post ART era there has been no substantial decline in HPV infections.

Human Papilloma Virus (HPV) is a conserved DNA virus, which infects mucosal and cutaneous epithelia. Although over 200 types of HPV have been identified which can infect humans, only around 15 high-risk (HR) types have been shown to be responsible for the development of cancer. HPV-16 is the most abundant HR-HPV type being responsible for almost 70% of cervical cancers. HPV-16 consists of 8 genes, the early genes (E1, E2, E4, E5 and the potential oncogenes E6 and E7) responsible for the infection, amplification and proliferation and the late genes (L1 and L2) responsible for the packaging and assembly of the virus. Autophagy, a physiological mechanism of intracellular digestion and recycling of unwanted cellular materials such as aggregated proteins and organelles has been shown to act as a first line defence against invading pathogens. An essential condition for this process is the formation of double membrane structures called the autophagosomes, which can engulf the pathogen or pathogenic proteins and digest them by fusing with endocytic vesicles (lysosomes). Beclin 1 and LC3 are vital proteins involved in the complicated process of the autophagosome formation while SQSTM1/p62 has a key role in the identification and transit of cargo into the forming autophagosomes. This novel work focuses on investigating the role of autophagy in HR-HPV related tumour development and progression in cervical epithelial cells both in vitro and ex vivo.

Thesis (Ph. D.)--University of Wisconsin, 1964. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

No description available.

The bovine papilloma virus type 2 (BPV-2) L2 open reading frame (ORF) was cloned into a λ pL promoter expression vector. This clone was shown to express a fusion protein which comprised 75% of the BPV-2 ORF linked to the first 13 N-terminal amino acids of the λ cIl gene product. Antisera was generated against this fusion protein and subsequently used to identify the L2 gene product as a 64,000 dalton protein in BPV-2 virions. It was also demonstrated that the L2 viral protein was present in full caps ids, but only in very limited amounts in empty caps ids. Densitometer analysis indicated that the L2 protein comprised only 8% of the total L1 + L2 "Coomassie blue stainable" protein in full capsids. The antisera was also used to demonstrate that the BPV-2 L2 gene product is antigenically related to the BPV-1 L2 gene product. Finally, an attempt was made to determine the location of the L2 gene product within the capsid structure. Hemagglutination inhibition and enzyme-llnked-immunosorbent- assay data both indicate that the L2 protein is exposed on the surface of the capsid. Immune electron microscopy data was inconclusive in determining the location of the L2 gene product.