Analysis on long-term trends of cervical cancer mortality and years of life lost in Tianjin, 1999-2015 / 中华流行病学杂志

Objective To analyze the mortality and years of life lost (YLL) trends of cervical cancer in Tianjin,and provide references for the research and prevention programs of cervical cancer.Methods Mortality rate,standard mortality rate,cumulative rate (0-74 years-old) and truncated rate (35-64 years-old) of cervical cancer from 1999 to 2015 were calculated.The annual percentage change of the mortality rate and YLL rate were analyzed by using Joinpoint regression analysis,and the trend in different age-groups were analyzed.Results From 1999 to 2015,1 741 cases died of cervical cancer in Tianjin,the average crude mortality rate was 2.15/100 000.The average age-standardized rate of (ASR) China and ASR world were 1.47/100 000 and 1.50/100 000 respectively.The average YLL was 3 347.97 person-years.Deaths occurred in those aged 0-34 years,35-64 years and 65 years and over accounted for 3.10％,57.84％ and 39.06％ of the total,respectively.The mortality rate of cervical cancer in urban area was higher than that in rural area,with a ratio of 1.37 ∶ 1 between urban area and rural area.The age-specific mortality rate of cervical cancer during 1999-2015 increased with age.Two peaks of mortality rate were observed in those aged 50 years and aged 75 years,during 2014-2015.From 1999 to 2011,the mortality rate of cervical cancer was stable (APC =-0.2％,P=0.80),but there was a rapid increase from 2011 to 2015 (APC=21.6％,P＜0.01).But group aged 20-49 years,it showed an upward trend from 1999 to 2015 (APC=6.9％,P＜0.01).For group aged 50-69 years,it showed a downward trend from 1999 to 2007 (APC=-9.2％,P＜0.01),and an upward trend from 2007 to 2015 (APC=14.5％,P＜0.01).For group aged 70 years and over,it showed a downward trend from 1999 to 2009 (APC=-10.2％,P＜0.01),but the difference in the mortality were not significant from 2009 to 2015 (APC=7.8％,P=0.10).Since 2008,the YLL rate of cervical cancer in group aged 50-70 years had exceeded that in group aged ＞70 years and the gap gradually widened.Conclusions There had been a rapid increase trend of cervical cancer mortality since 2011 in Tianjin.Women aged 50-70 years were the main group of life loss.

Analysis on long-term trends of cervical cancer mortality and years of life lost in Tianjin, 1999-2015 / 中华流行病学杂志

Objective To analyze the mortality and years of life lost (YLL) trends of cervical cancer in Tianjin,and provide references for the research and prevention programs of cervical cancer.Methods Mortality rate,standard mortality rate,cumulative rate (0-74 years-old) and truncated rate (35-64 years-old) of cervical cancer from 1999 to 2015 were calculated.The annual percentage change of the mortality rate and YLL rate were analyzed by using Joinpoint regression analysis,and the trend in different age-groups were analyzed.Results From 1999 to 2015,1 741 cases died of cervical cancer in Tianjin,the average crude mortality rate was 2.15/100 000.The average age-standardized rate of (ASR) China and ASR world were 1.47/100 000 and 1.50/100 000 respectively.The average YLL was 3 347.97 person-years.Deaths occurred in those aged 0-34 years,35-64 years and 65 years and over accounted for 3.10％,57.84％ and 39.06％ of the total,respectively.The mortality rate of cervical cancer in urban area was higher than that in rural area,with a ratio of 1.37 ∶ 1 between urban area and rural area.The age-specific mortality rate of cervical cancer during 1999-2015 increased with age.Two peaks of mortality rate were observed in those aged 50 years and aged 75 years,during 2014-2015.From 1999 to 2011,the mortality rate of cervical cancer was stable (APC =-0.2％,P=0.80),but there was a rapid increase from 2011 to 2015 (APC=21.6％,P＜0.01).But group aged 20-49 years,it showed an upward trend from 1999 to 2015 (APC=6.9％,P＜0.01).For group aged 50-69 years,it showed a downward trend from 1999 to 2007 (APC=-9.2％,P＜0.01),and an upward trend from 2007 to 2015 (APC=14.5％,P＜0.01).For group aged 70 years and over,it showed a downward trend from 1999 to 2009 (APC=-10.2％,P＜0.01),but the difference in the mortality were not significant from 2009 to 2015 (APC=7.8％,P=0.10).Since 2008,the YLL rate of cervical cancer in group aged 50-70 years had exceeded that in group aged ＞70 years and the gap gradually widened.Conclusions There had been a rapid increase trend of cervical cancer mortality since 2011 in Tianjin.Women aged 50-70 years were the main group of life loss.

Cervical cytology, HPV DNA and mRNA - a comparative study in 162 patients / Citologia cervicovaginal, DNA HPV e RNAm - estudo comparativo em 162 pacientes

In contrast to the general improvement of the socioeconomic status of the Brazilian population, pathologies that are characteristic of poor health assistance persist. Among those, cervical cancer (CC) is emblematic; it still presents a persistently high incidence. Objective: to compare the performance of cervical cytology to HPV DNA and mRNA detection methods in 162 patients undergoing routine gynecological clinical practice. Methods:a total of 162 patients attended during routine gynecological examination in a private clinic in Florianópolis, Santa Catarina, Brazil, had cervical samplescollected and processed for cytopathological and molecular tests, conventional PCR and NASBA. Positive samples positive for HPV DNA were submittedto Type-Specific PCR (TS-HPV PCR). Patients with altered smears were submitted to colposcopy and biopsy. Results: among the 162 samples, 19.8%(32/162) had altered smears, being 4/32 classified as ASC-H, 9/32 as ASC-US, 9/32 as LSIL and 10/32 as HSIL. Biopsies revealed nine cases of CIN I,nine CIN II and one CIN III, while seven were negative for cervical neoplasia. Overall, HPV DNA was detected in 38.3% (62/162) of the samples and HPV E6/E7 mRNA expression was found in 13.6% (22/162). Using TS-HPV PCR, HPV 16 was the most frequent type, found in 8% of the samples (5/62).Considering CIN2+ the gold-standard, cytology had 38.5% of specificity. Sensitivity and specificity of HPV-DNA PCR and NASBA were, respectively,100% and 60%; 18.7% and 68.7%. Conclusion: mRNA E6/E7 expression was not a highly specific or sensitive marker for prevalent cervical disease while HPV DNA may be used for cervical cancer screening only in conjunction to more specific adjuvant tests.

Em contraste com a melhora geral da situação socioeconômica da população brasileira, patologias que são características de uma deficiente assistência à saúde persistem. Entre elas, o câncer cervical (CC) é emblemático, ainda apresentando uma persistente alta incidência. Objetivo: avaliaro desempenho da citologia e de métodos de detecção de DNA e RNAm de HPV em 162 pacientes submetidas a prática clínica ginecológica de rotina.Métodos: cento e sessenta e duas pacientes atendidas em uma clínica particular de Florianópolis, Santa Catarina, Brasil, tiveram amostras cervicais coletadas e processadas para estudo citopatológico e molecular; PCR convencional e NASBA. Amostras positivas para o DNA do HPV foram submetidas àPCR tipo-específica (PCR HPV-TE). Resultados: entre as 162 amostras, 19,8% (32/162) apresentaram esfregaços alterados, sendo 4/32 classificadas comoASC-H, 9/32 como ASC-US, 9/32 como LSIL e 10/32 como HSIL. Biópsias revelaram nove casos de NIC I, nove casos de NIC II e um caso de NIC III. ODNA do HPV foi detectado em 38,3% (62/162) das amostras. Expressão de E6/E7 (RNAm) foi encontrada em 13,6% (22/162) das amostras. Utilizando a PCR tipo-específica (HPV-TE), o HPV 16 foi o tipo mais frequente, encontrado em 8% (5/62) das amostras HPV+. Considerando NIC 2+ o padrão-ouro,a especificidade da citologia foi de apenas 38,5%, enquanto a sensibilidade e a especificidade da PCR DNA e RNAm foram, respectivamente, 100% e 60%;18,7% e 68,7%. Conclusão: a expressão de E6/E7 RNAm não se mostrou um marcador altamente específico ou sensível para doença cervical prevalente,enquanto o DNA HPV pode ser utilizado para rastreamento apenas em conjunto com testes adjuvantes mais específicos.

Caracterização de metaloproteinases de matriz e reck em queratinócitos primários que expressam oncoproteínas do papilomavírus humano (HPV) / Characterization of matrix metalloproteinases and reck in primary keratinocytes that express human papillomavirus (HPV) oncoproteins

Os tumores da cérvice-uterina, que representam uma das principais doenças ginecológicas em mulheres na idade reprodutiva em todo o mundo, estão etiologicamente associados com a infecção pelo papilomavírus humano (HPV). A progressão de uma lesão intraepitelial escamosa de baixo-grau (LSIL) a um carcinoma invasivo de cérvix uterina está acompanhada da degradação da matriz extracelular (MEC) devido à ação progressiva das metaloproteinases de matriz (MMP-2, MMP-9 e MMP-14) no processo de invasão e metástase. Entretanto, o balanço entre as MMPs e seus reguladores como RECK e TIMPs é necessário para controlar esta invasão. O objetivo deste projeto consiste em avaliar a atividade e a expressão das metaloproteinases 2, 9, e 14, e caracterizar a expressão do gene supressor de metástase RECK e do inibidor tecidual de metaloproteinases (TIMP-2), em modelo de queratinócitos humanos infectados com retrovírus recombinantes que expressam os oncogenes E6 e/ou E7 de HPV 16, em culturas cultivadas em monocamada e organotípicas. Para isso, utilizamos ensaios de real-time PCR, zimografia, western blot, imunocitoquímica, ensaio de ELISA e imunohistoquímica. Em culturas em monocamada observamos que as células que expressam as oncoproteínas E6E7 de HPV16 apresentaram menores níveis protéicos de RECK e TIMP-2 em relação ao controle pXLSN. Quando analisamos as culturas organotípicas, também observamos esta diminuição dos níveis de RNAm e protéicos de RECK em rafts que expressam E6E7, acompanhado pelo aumento da atividade de MMP-9, em relação ao controle. Também observamos que o tratamento das culturas com a citocina TNF aumenta a expressão gênica, protéica e atividade de MMP-9 em todas as linhagens analisadas. Além disso, os oncogenes E6 e/ou E7 não afetam a expressão e/ou atividade de MMP-2, MT1-MMP. Nossos dados demonstraram que a expressão das oncoproteínas E6E7 de HPV16 estão relacionadas com o desequilíbrio entre MMPS e seus inibidores, sugerindo que em uma fase pré-invasiva do...

Cervical cancer is etiologically associated with to high-risk human papillomavirus (HPV) infection. It has been observed that matrix metalloproteinases (MMPs) -2, -9, and MT1-MMP are required for basement membrane degradation during cervical carcinoma progression. Moreover, a counterbalancing among MMPs and their regulators, such as TIMPs and RECK, is necessary to modulate invasion. In order to study the effect of HPV oncogenes on MMPs expression, primary human keratinocytes (PHKs) were infected with recombinant retroviruses expressing wild-type HPV16 E6 and/or E7 oncogenes and were used to seed monolayers and organotypic cultures. Quantitative real-time PCR (Q-PCR), western blot, zimography, immunocitochemistry, ELISA assay and immunohistochemistry were used to determine the expression level and activity of MMP-2, MMP-9, MT1-MMP and their inhibitors RECK and TIMP-2. We observed that cultures expressing E6E7 presented lower RECK and TIMP-2 protein levels than control keratinocytes. In addition, rafts cultures presented the same lower RECK levels additionally presenting higher MMP-9 activity than control. Furthermore, we observed that expression of E6 and/or E7 proteins do not affect MMP-2 and MT1-MMP protein levels and/or activity. We also observed that TNF treatment enhance the MMP-9 gene and protein expression and activity in all studied cell lines. Taken together, our results demonstrate that HPV16E6E7 expression is related with the unbalance between MMPs and their inhibitors, suggesting that in the initial steps of HPV-related cervical disease, not only MMPs but also RECK and TIMP-2 are critical for tumor progression.

A proteína p16 é uma novo marcador para progressão neoplásica no colo uterino? / Is the protein p16 a new mark for neoplastic progression in the cervix?

A pesquisa para Papilomavírus humano (HPV) de alto risco é um importante instrumento no rastreamento do carcinoma cervical, juntamente com a citologia cérvico-vaginal. No entanto, existe uma necessidade de validação de marcadores moleculares para aumentar a especificidade desses testes para detecção de lesões intraepiteliais que podem progredir. A proteína p16 atua como supressora de tumor por bloquear as CDK4 e CDK6 mediadas pela fosforilação da pRb, resultando na inibição da transcrição E2F dependente e, consequente inibição da progressão do ciclo celular. Pesquisas utilizando teste imunohistoquímico para p16 tem mostrado sua positividade em praticamente 100% dos casos de HSIL, carcinomas escamosos e adenocarcinomas in situ, além de auxiliar nos nos casos de LSIL associados com HPV de alto risco, onde poderá estar sobre-expressa. A análise imunocitoquímica p16 pode também ser uma ferramenta útil nos casos em que a citologia é incapaz de distinguir HSIL de alterações inflamatórias, reativas ou mesmo de epitélio normal. A p16 pode ser um marcador molecular útil em casos de histologia e/ou citologia inconclusivos, estratificando pacientes de alto risco.

Radiation treatment of 60 patients with cervical lymph node metastatic squamous cell carcinoma from an unknown primary site / 中华放射肿瘤学杂志

Objective To evaluate the prognosis for patients with squamous cell carcinoma of cervical lymph node metastases from an unknown primary site who had different clinical stages and were irradiated to different fields. Methods The clinical date of 60 patients with cervical lymph node metastatic squamous cell carcinoma from an unknown primary site(no including patients with supraclavicular node metastases) were retrospectively analyzed. Results The overall 5-year survival rates(OSR) was 68.5%, the OSR of patients with N 1,N 2 and N 3 stage were 100%, 68.0% and 40.9% respectively(? 2=7.29,P=0.026). The OSR of patients with one lateral neck, whole neck and large fields irradiation were 66.5%, 74.5% and 54.6% respectively(? 2=1.38,P =0.501). The Cox proportional hazard model showed that clinical stages of cervical lymph node had an significant effect in patients survival(P=0.032). The 5-year local control rates(LCR) 65.6%, the LCR of patients with N 1,N 2 and N 3 stage were 100%, 63.2% and 34.6% respectively(? 2=5.51, P=0.064). The LCR of patients with one lateral neck, whole neck and large fields irradiation were 87.6%, 51.0% and 72.7% respectively(? 2=2.55, P =0.279). The 5-year subsequent appearance rates of occult primary cancer(SAR) was 21.2%, the SAR of patients irradiated by small(one lateral neck or whole neck) and large fields were 23.3% and 12.5% respectively(? 2=0.52, P =0.469). Conclusions The clinical stages of cervical lymph node is an important prognostic factor for survival and the local control rates has a decreasing trend as the stage increases. The subsequent appearance rates of occult primary cancer of patients irradiated by small fields has a higher trend than its of patients irradiated by large fields, but the control rates and survival rates have no significant difference in different fields irradiated.