Phase 1 study of HPV16-specific immunotherapy with E6E7 fusion protein and ISCOMATRIX (TM) adjuvant in women with cervical intraepithelial neoplasia

Purpose: Persistent infection of cervical epithelium with high risk human papillomavirus (HPV) results in cervical intraepithelial neoplasia (CIN) from which squamous cancer of the cervix can arise. A study was undertaken to evaluate the safety and immunogenicity of an HPV 16 immunotherapeutic consisting of a mixture of HPV16 E6E7 fusion protein and ISCOMATRIX(TM) adjuvant (HPV16 Immunotherapeutic) for patients with CIN. Experimental design: Patients with CIN (n = 3 1) were recruited to a randomised blinded placebo controlled dose ranging study of immunotherapy. Results: Immunotherapy was well tolerated. Immunised subjects developed HPV16 E6E7 specific immunity. Antibody, delayed type hypersensitivity, in vitro cytokine release, and CD8 T cell responses to E6 and E7 proteins were each significantly greater in the immunised subjects than in placebo recipients. Loss of HPV16 DNA from the cervix was observed in some vaccine and placebo recipients. Conclusions : The HPV16 Immunotherapeutic comprising HPV16E6E7 fusion protein and ISCOMATRIX(TM) adjuvant is safe and induces vaccine antigen specific cell mediated immunity. (C) 2004 Elsevier Ltd. All rights reserved.

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

Background: Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials. Methods and Findings: Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93-1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93-1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82-1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76-1.10]). Conclusions: In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).

The epidemiology of basal cell carcinoma

Basal cell carcinoma (BCC) is a skin cancer of particular importance to the Australian community. Its rate of occurrence is highest in Queensland, where 1% to 2% of people are newly affected annually. This is an order of magnitude higher than corresponding incidence estimates in European and North American populations. Individuals with a sun-sensitive complexion are particularly susceptible because sun exposure is the single most important causative agent, as shown by the anatomic distribution of BCC which is in general consistent with the levels of sun exposure across body sites. A distinguishing feature of BCC is the occurrence of multiple primary tumours within individuals, synchronously or over time, and their diagnosis and treatment costs contribute substantially to the major public health burden caused by BCC. A primary knowledge gap about BCC pathogenesis however was an understanding of the true frequency of multiple BCC occurrences and their body distribution, and why a proportion of people do develop more than one BCC in their life. This research project sought to address this gap under an overarching research aim to better understand the detailed epidemiology of BCC with the ultimate goal of reducing the burden of this skin cancer through prevention. The particular aim was to document prospectively the rate of BCC occurrence and its associations with constitutional and environmental (solar) factors, all the while paying special attention to persons affected by more than one BCC. The study built on previous findings and recent developments in the field but set out to confirm and extend these and propose more adequate theories about the complex epidemiology of this cancer. Addressing these goals required a new approach to researching basal cell carcinoma, due to the need to account for the phenomenon of multiple incident BCCs per person. This was enabled by a 20 year community-based study of skin cancer in Australians that provided the methodological foundation for this thesis. Study participants were originally randomly selected in 1986 from the electoral register of all adult residents of the subtropical township of Nambour in Queensland, Australia. On various occasions during the study, participants were fully examined by dermatologists who documented cumulative photodamage as well as skin cancers. Participants completed standard questionnaires about skin cancer-related factors, and consented to have any diagnosed skin cancers notified to the investigators by regional pathology laboratories in Queensland. These methods allowed 100% ascertainment of histologically confirmed BCCs in this study population. 1339 participants had complete follow-up to the end of 2007. Statistical analyses in this thesis were carried out using SAS and SUDAAN statistical software packages. Modelling methods, including multivariate logistic regressions, allowed for repeated measures in terms of multiple BCCs per person. This innovative approach gave new findings on two levels, presented in five chapters as scientific papers: 1. Incidence of basal cell carcinoma multiplicity and detailed anatomic distribution: longitudinal study of an Australian population The incidence of people affected multiple times by BCC was 705 per 100,000 person years compared to an incidence rate of people singly affected of 935 per 100,000 person years. Among multiply and singly affected persons alike, site-specific BCC incidence rates were far highest on facial subsites, followed by upper limbs, trunk, and then lower limbs 2. Melanocytic nevi and basal cell carcinoma: is there an association? BCC risk was significantly increased in those with forearm nevi (Odds Ratios (OR) 1.43, 95% Confidence Intervals (CI) 1.09-1.89) compared to people without forearm nevi, especially among those who spent their time mainly outdoors (OR 1.6, 95%CI 1.1-2.3) compared to those who spent their time mainly indoors. Nevi on the back were not associated with BCC. 3. Clinical signs of photodamage are associated with basal cell carcinoma multiplicity and site: a 16-year longitudinal study Over a 16-year follow-up period, 58% of people affected by BCC developed more than one BCC. Among these people 60% developed BCCs across different anatomic sites. Participants with high numbers of solar keratoses, compared to people without solar keratoses, were most likely to experience the highest BCC counts overall (OR 3.3, 95%CI 1.4-13.5). Occurrences of BCC on the trunk (OR 3.3, 95%CI 1.4-7.6) and on the limbs (OR 3.7, 95%CI 2.0-7.0) were strongly associated with high numbers of solar keratoses on these sites. 4. Occurrence and determinants of basal cell carcinoma by histological subtype in an Australian community Among 1202 BCCs, 77% had a single growth pattern and 23% were of mixed histological composition. Among all BCCs the nodular followed by the superficial growth patterns were commonest. Risk of nodular and superficial BCCs on the head was raised if 5 or more solar keratoses were present on the face (OR 1.8, 95%CI 1.2-2.7 and OR 4.5, 95%CI 2.1-9.7 respectively) and similarly on the trunk in the presence of multiple solar keratoses on the trunk (OR 4.2, 95%CI 1.5-11.9 and OR 2.2, 95%CI 1.1-4.4 respectively). 5. Basal cell carcinoma and measures of cumulative sun exposure: an Australian longitudinal community-based study Dermal elastosis was more likely to be seen adjacent to head and neck BCCs than trunk BCCs (p=0.01). Severity of dermal elastosis increased on each site with increasing clinical signs of cutaneous sun damage on that site. BCCs that occurred without perilesional elastosis per se, were always found in an anatomic region with signs of photodamage. This thesis thus has identified the magnitude of the burden of multiple BCCs. It does not support the view that people affected by more than one BCC represent a distinct group of people who are prone to BCCs on certain body sites. The results also demonstrate that BCCs regardless of site, histology or order of occurrence are strongly associated with cumulative sun exposure causing photodamage to the skin, and hence challenge the view that BCCs occurring on body sites with typically low opportunities for sun exposure or of the superficial growth pattern are different in their association with the sun from those on typically sun-exposed sites, or nodular BCCs, respectively. Through dissemination in the scientific and medical literature, and to the community at large, these findings can ultimately assist in the primary and secondary prevention of BCC, perhaps especially in high-risk populations.

Occupational and non-occupational risk factors in bladder cancer patients in an industrialized area located in former East-Germany [Berufliche und außerberufliche Risikofaktoren für das Harnblasenkarzinom in einem ehemaligen Industriegebiet der neuen Bundesländer]

Purpose: Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e.g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1-2 carbon atoms) were investigated. Material and Methods: At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR. Results: Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1 %) was ordinary; the percentage of slow acetylators (59.6%) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8%) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative). Conclusions: The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis. [Article in German]

Cancer survivors at work : Work-related problems and factors associated with their employment, work ability and social support from the work community

Due to the improved prognosis of many forms of cancer, an increasing number of cancer survivors are willing to return to work after their treatment. It is generally believed, however, that people with cancer are either unemployed, stay at home, or retire more often than people without cancer. This study investigated the problems that cancer survivors experience on the labour market, as well as the disease-related, sociodemographic and psychosocial factors at work that are associated with the employment and work ability of cancer survivors. The impact of cancer on employment was studied combining the data of Finnish Cancer Registry and census data of the years 1985, 1990, 1995 or 1997 of Statistics Finland. There were two data sets containing 46 312 and 12 542 people with cancer. The results showed that cancer survivors were slightly less often employed than their referents. Two to three years after the diagnosis the employment rate of the cancer survivors was 9% lower than that of their referents (64% vs. 73%), whereas the employment rate was the same before the diagnosis (78%). The employment rate varied greatly according to the cancer type and education. The probability of being employed was greater in the lower than in the higher educational groups. People with cancer were less often employed than people without cancer mainly because of their higher retirement rate (34% vs. 27%). As well as employment, retirement varied by cancer type. The risk of retirement was twofold for people having cancer of the nervous system or people with leukaemia compared to their referents, whereas people with skin cancer, for example, did not have an increased risk of retirement. The aim of the questionnaire study was to investigate whether the work ability of cancer survivors differs from that of people without cancer and whether cancer had impaired their work ability. There were 591 cancer survivors and 757 referents in the data. Even though current work ability of cancer survivors did not differ between the survivors and their referents, 26% of cancer survivors reported that their physical work ability, and 19% that their mental work ability had deteriorated due to cancer. The survivors who had other diseases or had had chemotherapy, most often reported impaired work ability, whereas survivors with a strong commitment to their work organization, or a good social climate at work, reported impairment less frequently. The aim of the other questionnaire study containing 640 people with the history of cancer was to examine extent of social support that cancer survivors needed, and had received from their work community. The cancer survivors had received most support from their co-workers, and they hoped for more support especially from the occupational health care personnel (39% of women and 29% of men). More support was especially needed by men who had lymphoma, had received chemotherapy or had a low education level. The results of this study show that the majority of the survivors are able to return to work. There is, however, a group of cancer survivors who leave work life early, have impaired work ability due to their illness, and suffer from lack of support from their work place and the occupational health services. Treatment-related, as well as sociodemographic factors play an important role in survivors' work-related problems, and presumably their possibilities to continue working.

Prevalencia de la infección por papilomavirus humano en una población de baja incidencia de cancer de cuello uterino

182 p.

Avaliações econômicas do uso da vacina contra o Papilomavírus Humano (HPV) em meninas adolescentes: uma revisão sistemática

O câncer de colo do útero persiste como um importante problema de saúde em todo o mundo, em particular nos países em desenvolvimento. Duas vacinas contra o papilomavirus humano (HPV) encontram-se atualmente disponíveis e aprovadas para uso em meninas adolescentes, antes do início da vida sexual: uma bivalente, contra os sorotipos 16 e 18 e outra quadrivalente, contra os sorotipos 6, 11, 16 e 18. Estes imunobiológicos têm por objetivo induzir uma imunidade contra o papilomavírus e, desta forma, atuar na prevenção primária do câncer do colo de útero. As avaliações econômicas podem ser um elemento que auxiliem nos processos de tomada de decisão sobre a incorporação da vacina em programas de imunização nacionais. Estas avaliações foram o objeto central deste trabalho, que teve como objetivo sintetizar as evidências procedentes de uma revisão sistemática da literatura de estudos de avaliação econômica da utilização da vacina contra o HPV em meninas adolescentes e pré-adolescentes. Foi realizada uma busca na literatura nas bases MEDLINE (via Pubmed), LILACS (via Bireme) e National Health Service Economic Evaluation Database (NHS EED) ate junho de 2010. Dois avaliadores, de forma independente, selecionaram estudos de avaliação econômica completa, que tivessem como foco a imunização para HPV em mulheres com as vacinas comercialmente disponíveis direcionada à população adolescente. Após a busca, 188 títulos foram identificados; destes, 39 estudos preencheram os critérios de elegibilidade e foram incluídos na revisão. Por tratar-se de uma revisão de avaliações econômicas, não foi realizada uma medida de síntese dos valores de relação incremental entre custos e efetividade. Os 39 artigos incluídos envolveram 51 avaliações econômicas em 26 países. Predominaram estudos de custo-utilidade (51%). Do ponto de vista da perspectiva da análise, predominou o dos sistemas de saúde (76,4%). A maioria dos trabalhos (94,9%) elegeu meninas, com idade entre 9 e 12 anos, como sua população alvo e desenvolveu simulações considerando imunidade para toda a vida (84,6%). Os modelos utilizados nos estudos foram do tipo Markov em 25 análises, de transmissão dinâmica em 11 e híbridos em 3. As análises de sensibilidade revelaram um conjunto de elementos de incerteza, uma parte significativa dos quais relacionados a aspectos vacinais: custos da vacina, duração da imunidade, necessidade de doses de reforço, eficácia vacinal e cobertura do programa. Estes elementos configuram uma área de especial atenção para futuros modelos que venham a ser desenvolvidos no Brasil para análises econômicas da vacinação contra o HPV.

Distribuição geográfica das unidades laboratoriais, cobertura de exames e performance da rede de laboratórios que realiza rastreamento do câncer de colo de útero, segundo municípios do Estado do Rio de Janeiro.

O câncer de colo de útero é o terceiro tipo de neoplasia mais comum em mulheres no estado do Rio de Janeiro, perdendo apenas para câncer de mama e pulmão. Não há informação disponível sobre a qualidade dos exames utilizados para prevenção do câncer do colo do útero nos municípios fluminenses. O trabalho teve como objetivo avaliar a distribuição geográfica das unidades laboratoriais e a cobertura de exames e a performance da rede de laboratórios de citopatologia do estado do Rio de Janeiro, segundo regiões mesopolitanas e municípios, no que diz respeito aos exames citopatológicos realizados no âmbito do SUS, considerando a qualidade, a normalização dos procedimentos e a gestão do laboratório e propor melhorias. A pesquisa usa um desenho de estudo do tipo transversal incluindo dados relativos ao funcionamento dos laboratórios que fazem exame papanicolaou no âmbito do SUS no estado do Rio de Janeiro. Trata-se de um estudo com dados secundários, já coletados para atender a ação de avaliação dos laboratórios de citopatologia no âmbito do SUS, nesse trabalho também é usada a abordagem ecológica para estimar a cobertura dos exames em relação à população-alvo do programa de rastreamento de câncer de colo de útero. A rede de laboratórios de citopatologia do estado do Rio de Janeiro não teve desempenho satisfatório. As regiões que tiveram laboratórios com melhor desempenho foram Baia da Ilha Grande e Baixada Litorânea e aquelas com laboratórios de pior desempenho foram Médio Paraíba e Noroeste. Os critérios avaliados com melhor desempenho foram da dimensão qualidade e o mais fraco desempenho foi observado para os critérios da dimensão normalização. A dimensão de gestão de laboratórios teve desempenho regular. Um relevante achado desse estudo foi a insuficiente qualidade da leitura de lâminas, inclusive procedimentos de releitura, que pode ser explicado pela suposta falta de capacitação dos profissionais em todo o processo exigido desde a identificação, fixação, e formas de encaminhamento do material até a chegada aos laboratórios. Com relação à cobertura, alguns municípios se aproximam do parâmetro (0,30) porém, embora este dado revele a capacidade da rede estadual do rio de Janeiro de ofertar exames, é preciso que ele seja analisado em conjunto com as situações de citologia anterior e tempo da citologia anterior para verificação da periodicidade da oferta e o melhor dimensionamento do alcance da população alvo assim como a abrangência da rede laboratorial de cada município. Conclusão: Os dados mostram repetição desnecessária de exames citopatológicos, o que implica custos injustificados e uma situação ainda mais deficitária de alcance das ações do que tem revelado o indicador razão. Ocorrendo principalmente em regiões com predominância de laboratórios privados. A expansão da cobertura com base na periodicidade recomendada do exame é relevante no quadro estadual encontrado e deve vir associada a iniciativas que garantam a qualidade no processo de coleta e análise do material, bem como a adequada capacitação dos profissionais para adoção de condutas recomendadas para as lesões identificadas.

Magnitude da mortalidade por câncer do colo do útero no Brasil, 1996-2005

O presente estudo teve, por objetivo, corrigir a magnitude dos óbitos registrados por câncer do colo do útero no Brasil, e analisar a magnitude da mortalidade por este câncer e sua associação com indicadores sociais, nos estados da região Nordeste, Brasil, no período compreendido entre 1996 a 2005. Para a correção do sub-registro, foram utilizados os fatores criados pelo Projeto Carga Global de Doença no Brasil-1998. Metodologia de redistribuição proporcional foi utilizada para redistribuir as categorias de diagnósticos desconhecidas, incompletas ou mal definidas de óbitos identificadas no sistema de informação sobre mortalidade, exceto os dados ausentes de idade, corrigidos através de imputação. As correções foram aplicadas para cada Unidade Federativa do pais, segundo sexo e grupo etário, e os resultados apresentados para o Brasil e cada grande região e suas respectivas áreas geográficas (capital, demais municípios das regiões metropolitanas e interior). Tendências temporais de mortalidade foram analisadas através de regressão linear simples para cada estado da região Nordeste. Índice de variação percentual foi utilizado para determinar a variabilidade da magnitude das taxas, antes e após a correção dos óbitos. Através de regressão linear, foram analisados o comportamento da correção, e as correlações entre os indicadores socioeconômicos e as taxas de mortalidade por câncer do colo de útero sem e com correção. Após as correções, as taxas de mortalidade por câncer do colo do útero no Brasil mostraram um acréscimo percentual 103,4%, com variação de 35%, para as capitais da região Sul, a 339%, para o interior da região Nordeste. Foram encontradas correlações positivas entre alguns indicadores socioeconômicos e taxas sem correção, e correlações negativa entre esses mesmos indicadores e taxas corrigidas. Com outros indicadores socioeconômicos, observou-se o inverso dessa situação. Os resultados da correção apresentaram consistência em termos geográficos e em relação aos achados da literatura, permitindo concluir que a metodologia proposta foi adequada para corrigir a magnitude das taxas de mortalidade por câncer do colo do útero no país. Se analises comparativas sobre as condições socioeconômicas e o comportamento deste câncer forem estimadas sem quaisquer conhecimentos acerca da cobertura e qualidade de registro dos óbitos, pode-se incorrer a conclusões equivocadas. Considerando a magnitude corrigida da mortalidade por câncer do colo do útero, podemos afirmar que o problema desta doença na região Nordeste e no país, e mais grave do que o observado nos informes oficiais. Contudo, os resultados apontam que os programas de controle e detecção precoce desenvolvidos no país já mostram resultados positivos.

Dimensões relacionadas ao diagnóstico tardio do câncer do colo do útero: um estudo exploratório no Hospital do Câncer II / INCA

O objetivo deste estudo é o de conhecer e analisar a atenção em saúde de mulheres trabalhadoras com câncer do colo do útero avançado em tratamento no Hospital do Câncer II, no município do Rio de Janeiro. O estudo voltou-se para decifrar os diferentes momentos das trajetórias de vida e de trabalho dessas mulheres e relacioná-los com a procura dos serviços de saúde, estabelecendo relações com o acesso e a atenção à saúde. Constitui-se em um estudo exploratório, de natureza qualitativa, assentado em entrevistas e revisão teórico-bibliográfica. O aprofundamento teórico-empírico acerca deste tema buscou problematizar um objeto de estudo essencialmente relevante para o universo feminino, tendo em vista as altas taxas de incidência e mortalidade deste tipo de câncer no Brasil e no mundo sendo considerado, portanto, um problema de Saúde Pública. Os resultados apontam que o desconhecimento sobre o HPV e sobre a importância da realização do exame preventivo ainda é significativo entre as mulheres entrevistadas, o que aponta para a necessidade em priorizar o acesso à informação e a educação em saúde para o alcance de avanços no diagnóstico precoce. Também foram identificados como obstáculos na atenção em saúde, a sobrecarga de afazeres no cotidiano das mulheres, tendo em vista suas condições de vida e de trabalho e as dificuldades no acesso aos serviços de saúde.

Implementação de um sistema de rastreio do cancro do colo do útero com base na detecção do vírus HPV

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Human Papillomavirus and Oral Cancer: the International Agency for Research on Cancer Multicenter Study

Background: Human papillomavirus (HPV), the causal agent of cervical cancer, appears to be involved in the etiology of cancer of the oral cavity and oropharynx. To investigate these associations, we conducted a multicenter case-control study of cancer of the oral cavity and oropharynx in nine countries. Methods: We recruited 1670 case patients (1415 with cancer of the oral cavity and 255 with cancer of the oropharynx) and 1732 control subjects and obtained an interview, oral exfoliated cells, and blood from all participants and fresh biopsy specimens from case patients. HPV DNA was detected by polymerase chain reaction (PCR). Antibodies against HPV16 L1, E6, and E7 proteins in plasma were detected with enzyme-linked immunosorbent assays. Multivariable models were used for case-control and case-case comparisons. Results: HPV DNA was detected in biopsy specimens of 3.9% (95% confidence interval [CI]=2.5% to 5.3%) of 766 cancers of the oral cavity with valid PCR results and 18.3% (95% CI=12.0% to 24.7%) of 142 cancers of the oropharynx (oropharynx and tonsil combined) with valid PCR results. HPV DNA in cancer biopsy specimens was detected less frequently among tobacco smokers and paan chewers and more frequently among subjects who reported more than one sexual partner or who practiced oral sex. HPV16 DNA was found in 94.7% of HPV DNA-positive case patients. HPV DNA in exfoliated cells was not associated with cancer risk or with HPV DNA detection in biopsy specimens. Antibodies against HPV16 L1 were associated with risk for cancers of the oral cavity (odds ratio [OR]=1.5, 95% CI=1.1 to 2.1) and the oropharynx (OR=3.5, 95% CI=2.1 to 5.9). Antibodies against HPV16 E6 or E7 were also associated with risk for cancers of the oral cavity (OR=2.9, 95% CI=1.7 to 4.8) and the oropharynx (OR=9.2, 95% CI=4.8 to 17.7). Conclusions: HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity. The most common HPV type in genital cancers (HPV16) was also the most common in these tumors. The mechanism of transmission of HPV to the oral cavity warrants further investigation.

Risk of Malignant Progression in Barrett’s Esophagus Patients: Results from a Large Population-Based Study

Background: Barrett's esophagus (BE) is a premalignant lesion that predisposes to esophageal adenocarcinoma. However, the reported incidence of esophageal adenocarcinoma in patients with BE varies widely. We examined the risk of malignant progression in patients with BE using data from the Northern Ireland Barrett's esophagus Register (NIBR), one of the largest population-based registries of BE worldwide, which includes every adult diagnosed with BE in Northern Ireland between 1993 and 2005.

Subjects and Methods: We followed 8522 patients with BE, defined as columnar lined epithelium of the esophagus with or without specialized intestinal metaplasia (SIM), until the end of 2008. Patients with incident adenocarcinomas of the esophagus or gastric cardia or with high-grade dysplasia of the esophagus were identified by matching the NIBR with the Northern Ireland Cancer Registry, and deaths were identified by matching with records from the Registrar General's Office. Incidence of cancer outcomes or high-grade dysplasia was calculated as events per 100 person-years (% per year) of follow-up, and Cox proportional hazard models were used to determine incidence by age, sex, length of BE segment, presence of SIM, macroscopic BE, or low-grade dysplasia. All P values were from two-sided tests.

Results: After a mean of 7.0 years of follow-up, 79 patients were diagnosed with esophageal cancer, 16 with cancer of the gastric cardia, and 36 with high-grade dysplasia. In the entire cohort, incidence of esophageal or gastric cardia cancer or high-grade dysplasia combined was 0.22% per year (95% confidence interval [CI] = 0.19% to 0.26%). SIM was found in 46.0% of patients. In patients with SIM, the combined incidence was 0.38% per year (95% CI = 0.31 to 0.46%). The risk of cancer was statistically significantly elevated in patients with vs without SIM at index biopsy (0.38% per year vs 0.07% per year; hazard ratio [HR] = 3.54, 95% CI = 2.09 to 6.00, P <. 001), in men compared with women (0.28% per year vs 0.13% per year; HR = 2.11, 95% CI = 1.41 to 3.16, P <. 001), and in patients with low-grade dysplasia compared with no dysplasia (1.40% per year vs 0.17% per year; HR = 5.67, 95% CI = 3.77 to 8.53, P <. 001).

Conclusion: We found the risk of malignant progression among patients with BE to be lower than previously reported, suggesting that currently recommended surveillance strategies may not be cost-effective. © The Author 2011. Published by Oxford University Press. All rights reserved.

Early diagnosis improves survival in kidney cancer

Kidney cancers account for 2-3% of all adult malignancies in the UK. Men are predominantly affected by renal cancer with an average age at diagnosis of 64 years. Renal (or clear) cell carcinoma (RCC) accounts for 90% of kidney cancers. Early diagnosis improves survival with five-year survival rates for renal cancer of 70-94% for localised tumours in the UK. RCC should be suspected in the presence of localising symptoms such as flank pain, a loin mass or haematuria; constitutional upset including weight loss, pyrexia and/or night sweats; or with unexplained laboratory tests. Smoking, obesity and hypertension are the most important and most common risk factors. Environmental exposure to asbestos, cadmium and trichloroethylene are less common risk factors. Patients on chronic dialysis and renal transplant recipients are at increased risk of RCC in their native kidneys. If kidney cancer is suspected on history, physical examination or initial screening tests then a red flag ultrasound examination of the renal tracts should be requested. Dipstick urinalysis is of great value as asymptomatic haematuria may be the only abnormal test in the presence of non-specific symptoms such as weight loss or loin pain. Visible or non-visible haematuria, in the absence of proteinuria, suggests an underlying structural abnormality is present in the kidneys, ureters or bladder. Surgical removal of RCCs, where feasible, may result in cure in up to 40-60% of cases. Individuals too frail for major surgery may benefit from thermal ablation and cryotherapy. Agents that target the VEGF and mTOR pathways are considered first line in the treatment of metastatic RCC. Sunitinib, recommended by NICE, is administered orally and acts by inhibiting the VEGF receptor.