SerpinB2 (aka plasminogen activator type 2) is well described as an extracellular inhibitor of urokinase-type plasminogen activator (uPA). However, the majority of SerpinB2 is retained intracellularly, and many uPA-independent activities have been reported for SerpinB2 suggesting an alternate function. This thesis explores the role of SerpinB2 in epithelial tumour cell lines, highlights the problems associated with various expression systems and argues that SerpinB2 has no role in growth or apoptosis of tumour cells. A potential role for immune modulation and angiogenesis is suggested in in vivo models. Previous research using SerpinB2 transfected, clonally selected tumour cell lines suggested that SerpinB2 regulates the retinoblastoma tumour suppressor protein (Rb) by binding and protecting Rb from degradation. Despite the use of two techniques under numerous conditions and positive controls, no significant interaction between SerpinB2 and Rb was found. SerpinB2 was reported to bind Rb through a PENF homology motif located within the SerpinB2 C-D interhelical loop region. The PENF homology motif was postulated to represent the motif responsible for binding to the C-pocket of Rb. Epstein Barr Virus nuclear antigen 6 (EBNA6) is a known Rb binding protein, which contains two predicted PENF homology motifs. However, mutation of the two PENF homology motifs within EBNA6 did not reduce Rb binding. Furthermore, the SerpinB2 PENF homology motif is actually not well conserved between SerpinB2 proteins from multiple species, whereas other regions of the SerpinB2 C-D loop show a high level of conservation. These data do not support a role for SerpinB2 and the PENF homology motif in Rb binding. SerpinB2 has been proposed to have a role in regulating growth and apoptosis. To further investigate this proposed phenotype of SerpinB2, SerpinB2 was expressed in a range of epithelial tumour lines using transient transfection. No change in growth, apoptosis or Rb levels were found. After ≈2-3 month antibiotic selection for the SerpinB2-expressing plasmid, SerpinB2 protein was lost without the loss of the transgene, indicating selective pressure against long-term SerpinB2 protein expression. To further investigate long-term SerpinB2 expression adenovirus and lentivirus vectors were used. Infection of tumour cell lines with adenovirus vectors expressing SerpinB2 resulted in reduced cell growth, characterised by increased p53 (but not Rb) levels and G2 arrest or apoptosis. When SerpinB2 expressing lentivirus vectors were used to transduce the same tumour cell lines, high levels of long-term expression of functional SerpinB2 was achieved. However, SerpinB2-expressing cell lines showed no differences in growth, proliferation, Rb levels, or apoptosis induced by a range of agents. Growth and apoptosis observed with adenovirus SerpinB2 had all the characteristics of adenovirus-associated toxicity, which has been reported previously for specific proteins. These experiments highlighted the problems associated with SerpinB2 expression systems and suggest that SerpinB2 expression per se is not toxic nor has a role in regulating Rb, growth and apoptosis. Screening of a number of tumour cell lines identified the HPV16 transformed cervical cancer line as expressing high levels of SerpinB2. SerpinB2 was located both extracellularly and intracellularly with a cytoplasmic and nuclear distribution. A high molecular weight SerpinB2 species was identified in CaSki cells and was shown to be the N-linked glycosylated species. Sequencing showed the protein to be Type A SerpinB2 and the protein was shown to form an inhibitory complex with uPA. An abundant low molecular weight SerpinB2 species was also identified in CaSki cell supernatants and appeared to be a proteolytic fragment of SerpinB2. Treatment of CaSki with PMA, TNFα and IFNγ increased SerpinB2 levels. Lentiviral based shRNA failed to significantly down regulate SerpinB2 expression and increasing SerpinB2 levels with lentiviral expression did not change growth, apoptosis, Rb levels or E7 transcription. Lentiviral expression of SerpinB2 in (normally SerpinB2 negative) HPV16 transformed SiHa cells, also failed to show changes in Rb levels or E7 transcription. CaSki thus express wild-type and functional SerpinB2, but no evidence could found that SerpinB2 effects HPV16 E7 transcription or Rb levels. The data presented identifies CaSki as valuable source of biologically functional SerpinB2. SerpinB2 expression in breast cancer cells has been associated with positive prognosis. Tubo, a SerpinB2-negative murine breast carcinoma cell line, was transduced with lentivirus expressing SerpinB2 and grown subcutaneously in BALB/c mice. SerpinB2 expressing tumours appeared red and were larger than control tumours. Furthermore, SerpinB2 expressing tumours had a ≈2 fold higher density of blood vessels when compared to Tubo and Tubo expressing EGFP. Mice carrying tumours expressing SerpinB2 also showed reduced anti-tumour IgG2 responses. These data suggest that a role for SerpinB2 in regulating angiogenesis and antitumour immunity. In conclusion, this thesis challenges the notion that SerpinB2 regulates Rb, cell cycle, and apoptosis and suggests a potential role for SerpinB2 in tumour angiogenesis and immunity.

SerpinB2 (aka plasminogen activator type 2) is well described as an extracellular inhibitor of urokinase-type plasminogen activator (uPA). However, the majority of SerpinB2 is retained intracellularly, and many uPA-independent activities have been reported for SerpinB2 suggesting an alternate function. This thesis explores the role of SerpinB2 in epithelial tumour cell lines, highlights the problems associated with various expression systems and argues that SerpinB2 has no role in growth or apoptosis of tumour cells. A potential role for immune modulation and angiogenesis is suggested in in vivo models. Previous research using SerpinB2 transfected, clonally selected tumour cell lines suggested that SerpinB2 regulates the retinoblastoma tumour suppressor protein (Rb) by binding and protecting Rb from degradation. Despite the use of two techniques under numerous conditions and positive controls, no significant interaction between SerpinB2 and Rb was found. SerpinB2 was reported to bind Rb through a PENF homology motif located within the SerpinB2 C-D interhelical loop region. The PENF homology motif was postulated to represent the motif responsible for binding to the C-pocket of Rb. Epstein Barr Virus nuclear antigen 6 (EBNA6) is a known Rb binding protein, which contains two predicted PENF homology motifs. However, mutation of the two PENF homology motifs within EBNA6 did not reduce Rb binding. Furthermore, the SerpinB2 PENF homology motif is actually not well conserved between SerpinB2 proteins from multiple species, whereas other regions of the SerpinB2 C-D loop show a high level of conservation. These data do not support a role for SerpinB2 and the PENF homology motif in Rb binding. SerpinB2 has been proposed to have a role in regulating growth and apoptosis. To further investigate this proposed phenotype of SerpinB2, SerpinB2 was expressed in a range of epithelial tumour lines using transient transfection. No change in growth, apoptosis or Rb levels were found. After ≈2-3 month antibiotic selection for the SerpinB2-expressing plasmid, SerpinB2 protein was lost without the loss of the transgene, indicating selective pressure against long-term SerpinB2 protein expression. To further investigate long-term SerpinB2 expression adenovirus and lentivirus vectors were used. Infection of tumour cell lines with adenovirus vectors expressing SerpinB2 resulted in reduced cell growth, characterised by increased p53 (but not Rb) levels and G2 arrest or apoptosis. When SerpinB2 expressing lentivirus vectors were used to transduce the same tumour cell lines, high levels of long-term expression of functional SerpinB2 was achieved. However, SerpinB2-expressing cell lines showed no differences in growth, proliferation, Rb levels, or apoptosis induced by a range of agents. Growth and apoptosis observed with adenovirus SerpinB2 had all the characteristics of adenovirus-associated toxicity, which has been reported previously for specific proteins. These experiments highlighted the problems associated with SerpinB2 expression systems and suggest that SerpinB2 expression per se is not toxic nor has a role in regulating Rb, growth and apoptosis. Screening of a number of tumour cell lines identified the HPV16 transformed cervical cancer line as expressing high levels of SerpinB2. SerpinB2 was located both extracellularly and intracellularly with a cytoplasmic and nuclear distribution. A high molecular weight SerpinB2 species was identified in CaSki cells and was shown to be the N-linked glycosylated species. Sequencing showed the protein to be Type A SerpinB2 and the protein was shown to form an inhibitory complex with uPA. An abundant low molecular weight SerpinB2 species was also identified in CaSki cell supernatants and appeared to be a proteolytic fragment of SerpinB2. Treatment of CaSki with PMA, TNFα and IFNγ increased SerpinB2 levels. Lentiviral based shRNA failed to significantly down regulate SerpinB2 expression and increasing SerpinB2 levels with lentiviral expression did not change growth, apoptosis, Rb levels or E7 transcription. Lentiviral expression of SerpinB2 in (normally SerpinB2 negative) HPV16 transformed SiHa cells, also failed to show changes in Rb levels or E7 transcription. CaSki thus express wild-type and functional SerpinB2, but no evidence could found that SerpinB2 effects HPV16 E7 transcription or Rb levels. The data presented identifies CaSki as valuable source of biologically functional SerpinB2. SerpinB2 expression in breast cancer cells has been associated with positive prognosis. Tubo, a SerpinB2-negative murine breast carcinoma cell line, was transduced with lentivirus expressing SerpinB2 and grown subcutaneously in BALB/c mice. SerpinB2 expressing tumours appeared red and were larger than control tumours. Furthermore, SerpinB2 expressing tumours had a ≈2 fold higher density of blood vessels when compared to Tubo and Tubo expressing EGFP. Mice carrying tumours expressing SerpinB2 also showed reduced anti-tumour IgG2 responses. These data suggest that a role for SerpinB2 in regulating angiogenesis and antitumour immunity. In conclusion, this thesis challenges the notion that SerpinB2 regulates Rb, cell cycle, and apoptosis and suggests a potential role for SerpinB2 in tumour angiogenesis and immunity.

AIM & OBJECTIVES: Human papilloma virus (HPV) has been related to cervical infection, however, its part in Head and Neck Squamous Cell Carcinoma (HNSCC) is still debatable and is easy to refute. Suspicion of HPV causation is heightened when carcinomas arise in patients that are young and have never smoked. The present UK based study undertaken at Northampton NHS Trust endeavoured to determine the extent to which HPV is an entity in HNSCC in the UK. Furthermore, the study investigated whether sexual behaviour (as measured by sexual health clinic (SHC) attendance) is linked the acquisition of HPV associated HNSCC in young age groups. HNSCC incidences and sexual trends in the UK were collected from publicly available databases to identify if there were any changes at a national level in sexual behaviours and their influence on HNSCC in young age groups. MATERIALS & METHODS: PCR was used to evaluate the presence of HPV in biopsy samples from of 99 patients diagnosed with HNSCC at Northampton Hospital from 2006 to 2014. Patient demographics on age, sex, smoking, alcohol use and SHC attendance were also collected. All HPV PCR positive biopsies were further genotyped using an ABI 3130xl genetic analyser. Databases in the UK; including GLOBOCAN, NATSAL and PHE were searched for data on HNSCC prevalence, sexual behaviour trends and vaccine uptake. Multinomial regression explored the relationship between HPV positivity and sex, age, smoking, drinking, race and SHC attendance. RESULTS: PCR showed that 25.2% (25/99) of biopsies tested were positive for HPV and were all obtained from white participants. Most specimens (23, 92%) were high-risk (HR) HPV 16 positive with a mean age of 56 for HPV positivity and 72% of the cases 50-60 years old. Smokers were 11% in total (11/99) with most 88.9% participants (88/99) being non-smokers. HPV positivity was strongly linked with non-smoking history (p < 0.001); no alcohol abuse (p < 0.001); male gender (p < 0.001); young age less than 60 years (p < 0.001) and SHC attendance (p < 0.001). A Kruskal-Wallis post hoc test affirmed the impact of age on HPV positivity (p= < 0.05). GLOBOCAN and Cancer Research demonstrated a rising UK HNSCC pattern of over 200% for both sexes from 1975 to 2011. The three NATSAL surveys undertaken in 1990-1991, 1999-2001 and 2010-2012 demonstrated an overall increase in opposite and same sex partners. The UK average of individuals engaging in oral sex was in the younger age groups of between 16 and 54 with at least 70% of males and 63% females of that age engaging in oral sex. Finally, NASTAL 1, 2 and 3 surveys reported 20 vs 15; 25 vs 55; 55 vs 65 of males and females respectively with more than 10 sexual partners to have attended the SHC. The UK immunization take-up was over 90% countrywide. CONCLUSION: Few research studies have been conducted to date on HPV as a cause of HNSCC in the UK. The present research showed 25.2% of HNSCC to be caused by HPV, with the high risk (HR) genotype 16 (the leading cause of cervical cancer) accounting for 92% (23/25) of the cases. These outcomes affirmed the high prevalence of HR-HPV in HNSCC, with a rate of 25.2% similar to those reported previously. Routine HPV testing in those aged below 60 is therefore warranted. Smoking and drinking showed negative correlation; the young age of below 60 and attendance of the SHC for both sexes showed a positive correlation with HPV positive HNSCC. NATSAL data showed increased sexually risky behaviour coupled with attending the SHC in younger ages for both sexes. Increased sexually risky behaviour as shown in NASTAL surveys may be the reason why young age and SHC attendance is positively correlated with HPV HNSCC. The study highlights a conceivable relationship between HPV positive HNSCC in those under 60 years with no smoking history who attended the SHC. Smoking and drinking are known risks for HNSCC in those past 65 years of age; the negative association with HPV HNSCC in the young in the present research revealed smoking and drinking to have reduced association with HPV HNSCC. The reported HR-HPV positive HNSCC in young age groups inform future vaccination strategies and consequently decrease the quantity of HPV HNSCC's.

Background: The HPV vaccine has been introduced to the public and the medical community since June 2006 for the vaccination of females and since November 2009 for the vaccination of males ages 9-26 years old. The purposes of this research were to explore multiple factors and relationships among Health Belief Model (HBM) constructs (perceived susceptibility, perceived severity, perceived barriers, and perceived benefits) and mediating factors (self-efficacy and cues to action) related to HPV, HPV-associated diseases, and HPV vaccine among Russian college students and to determine which factors were most important when considering who would/would not seek HPV vaccination. Methods: A quantitative, cross-sectional, descriptive, and correlational survey design was used in this study. An existing self-report questionnaire HPV Study Survey was adapted with the permission from the author. One thousand two hundred participants were contacted by Yaroslav-the-Wise Novgorod State University, Veliky Novgorod, Russia registrar's office through e-mails and messaging using two social networks through simple random sampling method using the SQL statement "ORDER BY NEWID" propriety of Microsoft algorithm out of the total student population (9,923 students). The survey was distributed through SurveyMonkeyTM survey software that was activated December 2011 - April 2012. Results: Two hundred seventy students replied to the survey (22.5% response rate) and 117 participants fully completed it out of 270 who responded to the survey (43.33% completion rate). The initial response rate increased 4.4 times using social networks messaging compared to e-mailing invitations. Overall, average knowledge levels were moderate. Participants' behaviors regarding their sexual activity showed that the majority of participants were sexually active. Participants' perceptions (susceptibility, severity, barriers, and benefits) and mediating factors (cues to action and self-efficacy) were moderate. Participants' behavioral intention to get HPV vaccination was moderate. There were statistically significant differences between males and females in perceived susceptibility, perceived barriers, self-efficacy, behavioral intention, and in three behavioral items (having had sexual contact; age of having had sexual contact and sex for the first time). Sixty percent of the variance in behavioral intention getting HPV vaccination could be explained by two HBM constructs (perceived benefits and self-efficacy). Self-efficacy was the number one predictor of behavioral intention (p < 0.001) and perceived benefits were the number two predictor of behavioral intention (p < 0.01).

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-07-19T17:43:23Z No. of bitstreams: 1 Geise Paiva. Carcinoma de pênis.pdf: 1212270 bytes, checksum: f6aea41a94c500d0761c9c32a738597a (MD5) / Made available in DSpace on 2012-07-19T17:43:23Z (GMT). No. of bitstreams: 1 Geise Paiva. Carcinoma de pênis.pdf: 1212270 bytes, checksum: f6aea41a94c500d0761c9c32a738597a (MD5) Previous issue date: 2010 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / O câncer de pênis é um problema de saúde pública principalmente em países em desenvolvimento. No Brasil, a incidência é alta e as regiões Nordeste e Sudeste são as mais afetadas, concentrando, respectivamente, 41,9% e 40,4% dos casos, segundo dados da Sociedade Brasileira de Urologia. Com o objetivo de conhecer melhor as características da doença no Estado, procedemos a revisão de prontuários e lâminas histológicas dos pacientes com a doença, atendidos do Hospital Aristides Maltez, Bahia, entre janeiro de 1997 a dezembro de 2007. Foram estudados 314 pacientes, a média de idade foi de 57 anos, 45% dos pacientes eram analfabetos e pacientes pardos representaram 83,8% da amostra. Amputação foi o procedimento mais comum, realizado em 288 casos (74,1%), linfadenectomias foram realizadas em 77 pacientes. Alterações histológicas sugestivas de infecção por HPV foram observadas em 239 (75,9%) pacientes. Segundo a classificação da OMS de 2004, o carcinoma usual foi o mais freqüente, com 241 (76,8%) casos e os subtipos representaram 23,2% da amostra. Dentre os subtipos, o misto e o Warty foram os mais observados, 29 (9,2%) e 26 (8,2%) e sarcomatóides e verrucosos foram os menos freqüentes, 1 (0,3%) e 2 (0,6%) dos casos, respectivamente. Observamos características clínicas semelhantes: baixo nível econômico e social, baixíssimo nível de instrução, predominância de pardos e negros, dificuldade de acesso aos serviços de saúde, tempo arrastado de sintomatologia, média de idade de 57 anos, além de altas taxas de infecção por HPV. Aspectos clínico-patológicos de mais de 300 pacientes foram apresentados e revistos segundo nova classificação da OMS de 2004. Nossa série é uma das primeiras a rever os casos segundo esta nova classificação, importante para prever a evolução destes tumores e auxiliar a clínicos e cirurgiões a estabelecer a melhor estratégia no tratamento. Conhecer o perfil da doença no Estado possibilita a criação de medidas voltadas à prevenção, diagnóstico e tratamento precoce para diminuir a incidência e morbidade desta triste realidade da doença em nosso país. Assim como permite a longo prazo a continuidade de um trabalho de investigação que possa responder a questões ainda não entendidas sobre a doença. / Penile Cancer is a public health problem mainly in developing countries. In Brazil, the incidence is higher in the Northeast and Southeast regions, respectively responsible for 41.9% and 40.4% of the cases, according to the Sociedade Brasileira de Urologia. Aiming to better understand the characteristics of this disease in our state, we proceeded reviewing medical records and histological slides of patients with the disease who were treated at the Hospital Aristides Maltez, Bahia, between January 1997 and December 2007. We studied 314 patients, with average age of 57 years, 45% were illiterate and mulatto patients accounted for 83.8% of the sample. Amputation was the most commonly procedure performed in 288 cases (74.1%), lymphadenectomy was performed in 77 patients. Histological changes suggestive of HPV infection were observed in 239 (75,9%) patients. According to the WHO classification of 2004, the usual carcinoma was the most frequent, with 241 (76.8%) cases and the other subtypes accounted for 23.2% of the sample. Among the subtypes, warty and mixed were the most frequently observed, 29 (9.2%) and 26 (8.2%) and sarcomatoid and verrucous were the least frequent, 1 (0.3%) and 2 (0.6%) of the cases, respectively. We observed similar characteristics: low economic and social, very low level of education, a predominance of brown and black skin, limited access to health services, time dragged symptoms, average age of 57 years and high rates of HPV infection. Clinical and pathological aspects of more than 300 patients were presented and reviewed following the new WHO classification of 2004. Our series is one of the first to review the cases under this new classification, important to predict the evolution of these tumors and help clinicians and surgeons to establish the best strategy for treatment. Knowing the profile of the disease in the state allows the creation of measures aiming prevention, early diagnosis and treatment to reduce the incidence and morbidity of this sad reality in our country. Allowing also long-term continuation

The theoretical part summarizes information about cervical cancer, which is caused by the human papilloma virus. Cervical cancer is ranked on the second place in the incidence of cancers world wide. Virus HPV affects both men and women. For men, it results in the emergence of genital warts or cancer of the penis. Although there are existing opportunites for effective prevention for men, the focus is more on the female population.This thesis looks at the current problems in the prevention of cervical cancer, which affects an ever growing number of women and men. In this work, we find out how informed are the young people about cervical cancer, their knowledge about possibilities of prevention, and experience of vaccinated respondents in the age in which this vaccination is recommended, that is, before the start of an active sexual life. In the research part, is a summary of a questionnaire, which was done among pupils of a primary school in Plzen. The age range of respondents was 13- 16 years. The research included both girls and boys. The assumption that girls are more informed and are more interested in information regarding cervical cancer and boys on the contrary don?t search for this information because they think that this problem does not concern them , was largely confirmed by this research.

Introdução: A endoscopia de contato (EC) foi um exame descrito inicialmente como método de analise da histologia uterina e das cordas vocais. Os primeiros estudos utilizando a EC nas cavidades nasais mostraram resultados promissores na diferenciação de lesões benignas, considerando que a biópsia tradicional pode trazer algumas complicações. Objetivo: Descrever e comparar os achados da EC no papiloma schneideriano invertido e no carcinoma espinocelular nasossinusal e testar a efetividade do exame como método não invasivo in vivo para diferenciação entre esses tumores. Métodos: Os pacientes inclusos no estudo foram divididos em grupo A, com diagnóstico de papiloma invertido e grupo B, com diagnóstico de carcinoma espinocelular. Os resultados da EC de cada lesão foram comparados entre si. As imagens gravadas dos exames foram apresentadas à examinadores sem experiência com a EC. Resultados: Um total de vinte e dois pacientes foram examinados, treze no grupo A e nove no grupo B. As principais diferenças nos achados da EC entre os dois grupos foram: presença de vasos espiralados, mitoses, queratinização e pleomorfismo nuclear no carcinoma e presença de células vacuolizadas no papiloma. Os examinadores, mesmo não habituados a este novo método, tiveram um bom índice de acerto no diagnóstico diferencial das duas lesões nasais, baseados apenas nas imagens da EC. Conclusão: A EC pode ser um exame não invasivo e in vivo útil para o diagnóstico diferencial entre o papiloma invertido e o carcinoma espinocelular nasossinusal, principalmente quando usado no planejamento pré-operatório do paciente. / Background: Contact endoscopy (CE) was initially described as a method used in the analysis of uterine and vocal folds histology. The first nasal cavity CE studies achieved promising results regarding its use for the differentiation between benign and malignant lesions, considering that biopsy might cause some complications, especially bleeding. Objective: Describe and compare the findings of CE on inverted papilloma and nasosinusal squamous cell carcinoma and test the effectiveness of this exam as a noninvasive method for in vivo differentiation between these tumors. Methods: The patients included in this study were divided into Group A, whose diagnosis was inverted papilloma, and Group B, whose diagnosis was squamous cell carcinoma. CE results were compared amongst themselves. CE images were presented to examiners not experienced with the method. Results: Twenty-two patients were examined, thirteen in Group A and nine in Group B. The main relevant differences in CE findings between those two groups were: corkscrew vessels, presence of mitoses, keratinization and nuclear pleomorphism in carcinoma, and vacuolated cells in papilloma. The examiners were capable of defining the diagnosis of these nasal tumors only based on CE images. Conclusion: CE may be a useful noninvasive exam to be used in the in vivo diagnosis of inverted papilloma and nasosinusal squamous cell carcinoma, which may enable better preoperative planning.

Os papilomavírus humanos (HPVs) oncogênicos são importantes agentes na etiologia do câncer ginecológico e atualmente tem sido relacionados também a algumas lesões cancerizáveis e a alguns tipos de cânceres de boca. Com o objetivo de avaliar a relação entre os HPVs e um tipo de lesão cancerizável de boca que acomete os lábios chamada queilite actínica crônica (QAC), foram avaliados e considerados aptos para a pesquisa 29 pacientes portadores de QAC. A reação em cadeia pela polimerase (PCR) foi utilizada para detectar a presença do HPV em amostras de tecido fresco, provenientes de lábios doentes onde todos os casos apresentaram resultados negativos. A QAC ocorreu em 100% nos indivíduos da raça branca, em 19 homens e 10 mulheres e na idade média de 56,14 anos. Foram avaliados também os aspectos clínicos e histológicos da QAC sendo encontrados 14 casos de atipia epitelial discreta (48,27%), 10 casos de atipia epitelial moderada (34,49%) e 5 casos de atipia epitelial severa (17,24%). Através de análise estatística concluímos que clinicamente a presença de áreas leucoplásicas e o tempo de evolução da lesão superior a 5 anos estão diretamente relacionados aos casos de atipias epiteliais mais graves. O hábito de fumar e de beber parecem contribuir, mas não obtiveram resultados estatisticamente significativos ao aparecimento da QAC. / The oncogenic human papillomaviruses (HPVs) are important agents in the etiology of gynecological cancer and have been recently related to some premalignant lesions and to some types of mouth cancer. In order to evaluate the relation between HPVs and one type of precancerous lesion that affects the lips called chronic actinic cheilitis (CAC), 29 CAC patients were assessed and considered eligible for the study. The polymerase chain reaction (PCR) was used to detect the presence of HPV in fresh tissue samples of affected lips. All results were negative. All CAC patients were Caucasian, 19 males and 10 women, mean age of 56.14 years. The clinical and histological aspects of CAC were also assessed - there were 14 cases of discreet (48.27%), 10 cases of moderate (34.49%) and 5 cases of severe epithelial atypia (17.24%). By statistical analysis we concluded that, clinically, the presence of leukoplastic areas and progression of the lesion for over five years are directly related to more severe epithelial atypia. Smoking and drinking habits seem to contribute to the condition but achieved no statistical significance regarding onset of CAC.

Introdução: A síndrome de Cowden é um distúrbio multissistêmico de predisposição a diversos tipos de câncer e padrão de herança autossômica dominante. As lesões cutâneas e viscerais são consideradas proliferações hamartomatosas ou tumores malignos. As lesões mucocutâneas estão presentes em quase 100% dos indivíduos afetados. No entanto, alguns autores consideram que as manifestações mucocutâneas da síndrome de Cowden são, na realidade, verrugas virais em diferentes estágios de evolução. Há poucos estudos sobre manifestações orais da síndrome de Cowden. Objetivos: Estudar as manifestações orais da síndrome de Cowden em 9 pacientes, clínica e histopatologicamente. Métodos: As lesões orais presentes em 9 pacientes com diagnóstico de síndrome de Cowden foram estudadas através de revisão de prontuário, fotografias e biopsias em seus distintos aspectos. Resultados: Todas as lesões biopsiadas mostraram aspectos histopatológicos característico de verrugas virais em diferentes estágios de evolução. Conclusão: Nossos achados parecem reforçar a hipótese de que as manifestações mucocutâneas da síndrome de Cowden representam, na realidade, verrugas virais. Estudos adicionais são necessários para explicar porque esta síndrome, causada por uma mutação de um gene supressor tumoral, poderia causar propensão a verrugas / Background: Cowden disease is a multisystemic cancer predisposition disorder, inherited in a autosomal dominant pattern. Cutaneous and visceral lesions are either malignant tumors or are believed to represent hamartomatous growths. Mucocutaneos lesions are present on almost 100% of affected individuals. Nonetheless, some authors consider that the mucocutaneous manifestations of Cowden disease are, in reality, viral warts at distinct steps of evolution. There are only a few studies regarding the oral manifestation of Cowden disease. Objectives: To study the oral manifestation of Cowden disease in nine patients clinically and histopathologically. Methods: The oral mucosal aspects of nine patients with clinical diagnosis of Cowden disease were studied by reviewing medical charts, photographs and biopsies in their different aspects. Results: All biopsied lesions depicted histopathological aspects suggestive of viral warts at distinct steps of development. Conclusion: Our findings seem to reinforce the poorly understood hypothesis that the mucocutaneous manifestations of Cowden disease are in reality viral warts. Additional studies are needed to explain why a syndrome caused by the mutation of a tumor suppression gene may cause propensity to warts

Thesis (M.A.) / INTRODUCTION: Cervical cancer exists as the second most common cancer among women world wide, and in numerous countries is the leading type of female cancer. Specifically, Zambia has one of the highest mortality rates and cervical cancer incidence rates. The goal of this study is to analyze the published literature on preventative techniques for cervical cancer in resource-deprived areas of sub-Saharan Africa by focusing on the correlation between the Human Papilloma Virus (HPV), Acquired Immunodeficiency Syndrome (AIDS), and cervical cancer; the accuracy and feasibility of “screen and treat” clinics; and socio-economic and geographical barriers. RESULTS: Correlations exists between the prevalence of HIV, HPV, and cervical cancer in sub-Saharan Africa, and a clear association exists between HPV and cervical cancer. The deliverance of HPV vaccines as well as educational programs has helped to improve this medical problem. Main screening methods for cervical cancer include the Pap smear, naked eye visual inspection of the cervix after the application of either diluted acetic acid (VIA), Lugol’s iodine (VILI), or with a magnifying device (VIAM), colposcopy, and tests for HPV markers. Studies indicate that the VILI screening test has the highest level of sensitivity with the LEEP method also of importance. The procedure is relatively low cost and is easy to implement when excising lesions. Major risk factors and determinants of cervical cancer can help to explain the underlying barriers of access to care. Women’s misconceptions regarding cervical cancer, gender inequality in African nations, socio-economic status, and foreign aid all play major roles the cervical cancer screening process. A lack of proper education, especially among women in sub-Sahara Africa, has led to misconceptions about the causes of cervical cancer. Studies have found that some women associated cervical cancer with prostitution, a Satanic curse, and other bad behavior. Gender inequality also plays a significant role since the Zambia government had reported that a husband would have absolute rights over children and reproductive rights over his wife once he had made payments for a bride. Geographical barriers also exist as the terrain in Zambia is swamp-like and heavy flooding throughout the year is common. After flooding occurs, communities become physically separated. Furthermore, there are correlations between high incidence rates of cervical cancer and high poverty as it has been shown that the largest number of people living on less than $1.25 dollars per day is that of sub-Saharan Africa. DISCUSSION: Studies have indicated that virtually all of cases of cervical cancer are caused by HPV, implying that HPV testing and detection would largely prevent the progression of lesions. Ultimately, this would reduce the high incidence rate of cervical cancer in Zambia and in other Sub-Saharan African countries. In areas where cytology programs are either non-existent or not efficient, HPV testing approaches should be evaluated and implemented, and they should be based off of the HIV/AIDS infrastructure that has already been established. In regards to the screening approaches, VIAM and VIA are the only two tests that are also practical, affordable, and available. Affordability is the major concern when implementing screening programs in sub-Saharan Africa; for this reason, either VIAM and VIA would arguably be the best options as long as they were effective. VIA would be considered the most appropriate method in terms of screening procedures as the method has the advantage of giving immediate results that can be applied to large populations. Lastly, the lack of proper education, including sex education, has in part led to drastic misconceptions about the causes of cervical cancer. Women hold negative beliefs about cervical cancer since they associate it with being unclean and view it as a reflection of bad behavior. Geographical barriers also play a role; the physical inaccessibility of the clinic discourages women to come to the clinic for screenings. Home visits by physicians and/or the utilization of community health workers may help to eliminate this particular barrier of access. This strategy would be especially beneficial to residents of rural areas since they are more likely to live farther away from institutionalized clinics and screen and treat facilities and are also more likely to be in a state of extreme poverty.