HPV vaccines: separating myths from reality

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Up-regulation of 14-3-3sigma (Stratifin) is associated with high-grade CIN and high-risk human papillomavirus (HPV) at baseline but does not predict outcomes of HR-HPV infections or incident CIN in the LAMS study

To assess whether the potentially high-risk (HR) human papillomavirus (HPV)-related up-regulation of 14-3-3sigma (stratifin) has implications in the outcome of HPV infections or cervical intraepithelial neoplasia (CIN) lesions, cervical biopsy specimens from 225 women in the Latin American Screening Study were analyzed for 14-3-3sigma expression using immunohistochemical analysis. We assessed its associations with CIN grade and HR HPV at baseline and value in predicting outcomes of HR-HPV infections and the development of incident CIN 1+ and CIN 2+. Expression of 14-3-3sigma increased in parallel with the lesion grade. Up-regulation was also significantly related to HR-HPV detection (P = .004; odds ratio, 2.71; 95% confidence interval, 1.37-5.35) and showed a linear relationship to HR-HPV loads (P = .003). 14-3-3sigma expression was of no value in predicting the outcomes (incident, persistent, clearance) of HR-HPV infections or incident CIN 1+ and CIN 2+. 14-3-3sigma is not inactivated in cervical carcinoma and CIN but is up-regulated on transition from CIN 2 to CIN 3. Its normal functions in controlling G(1)/S and G(2)/M checkpoints are being bypassed by HR HPV.LAMS, Latin American Screening Study, funded by European Commission, INCO-DEV contract ICA4-CT-2001-10013

Prevalência do HPV em mulheres rastreadas para o câncer cervical

OBJECTIVE: To assess the prevalence of high-risk genital human papillomavirus (HPV) infection by age group and risk factors associated. METHODS: Cross-sectional study in a sample of 2,300 women (15-65 years old) who self-referred to cervical cancer screening in Sao Paulo and Campinas, Southeastern Brazil, between February 2002 and March 2003. An epidemiological questionnaire was applied and cervical specimens were obtained for cytology and hybrid capture II test (HCII) for HPV detection. Statistical analysis included Pearson Chi-square and unconditional multiple logistic regression model (forward likelihood ratio). RESULTS: High-risk genital HPV infection prevalence in this sample was 17.8% and age distribution was as follows: 27.1% (OBJETIVO: Analisar a prevalência da infecção genital por papilomavírus humano (HPV) de alto risco por faixa etária e fatores associados. MÉTODOS: Estudo transversal com amostra de 2.300 mulheres (15-65 anos) que buscaram rastreamento para o câncer cervical entre fevereiro de 2002 e março de 2003 em São Paulo e Campinas, estado de São Paulo. Aplicou-se questionário epidemiológico e realizou-se coleta cervical para citologia oncológica e teste de captura híbrida II. As análises estatísticas empregadas foram teste de qui-quadrado de Pearson e análise multivariada pelo método forward likelihood ratio. RESULTADOS: A prevalência total da infecção genital por HPV de alto risco foi de 17,8%, distribuída nas faixas etárias: 27,1%

Incidence and Duration of Type-Specific Human Papillomavirus Infection in High-Risk HPV-Naïve Women: Results from the Control Arm of a Phase II HPV-16/18 Vaccine Trial

OBJECTIVES: Persistence of human papillomaviruses (HPVs) is necessary for cervical carcinogenesis. We evaluated incidence and duration of type-specific HPV infections and the influence of age and number of sexual partners. METHODS: Data were obtained from 553 women (15-25 years), who were seronegative and DNA-negative for high-risk HPV (HR-HPV) types and were enrolled in the placebo arm of a randomised trial of the HPV-16/18 vaccine (NCT00689741/NCT00120848). They were followed for 6.3 years. Cervicovaginal samples were self-collected at 3-month intervals for up to 27 months, and cervical samples were collected by clinicians at 6-month intervals until study end. Samples were tested for HPV types using a broad-spectrum PCR assay. Incidence rate ratios (RRs) and 95% CIs were used to estimate the association among age, sexual habits and HPV acquisition. RESULTS: Incidence rates (95% CI) using cervical samples were 11.8 (10.4 to 13.4) and 5.6 (4.7 to 6.6) per 1000 women-months for HR-HPVs and low-risk HPVs (LR-HPVs), respectively. Equivalent rates in combined cervicovaginal and cervical samples were 17.2 (15.4 to 19.2) and 6.9 (5.9 to 8.0), respectively. 54 per cent of HR-HPV types from combined cervicovaginal and cervical samples persisted for 1 year compared with 32.3% for LR-HPV types. The risk of acquiring any HPV infection was higher among women aged(RR=1.33, 95% CI 1.1 to 1.7) and women having \u3e1 sexual partner (RR=1.83, 95% CI 1.4 to 2.4) at baseline. CONCLUSIONS: HR-HPV infections were more common and lasted longer on average than LR-HPV infections. HPV acquisition was more common in younger women with multiple sexual partners

Analise dos criterios histologicos utilizados para diagnostico de lesão induzida por HPV e sua relação com a reatividade do DNA-HPV por captura de hibridos e por hibridização in situ

Orientadores: Sophie F. Mauricette Derchain, Venancio Avancini F. AlvesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasDoutorad

Fatores associados a neoplasia intraepitelial cervical grau 2 e 3 em mulheres com alterações da colpocitologia e da colposcopia sugestivas de infecção por papiloma virus humano

Orientadores: Sophie Françoise Mauricette Derchain, Kazue Panetta, Venancio Avancini Ferreira AlvesDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Os objetivos deste estudo foram avaliar a prevalência de NIC 2 e 3 em mulheres sexualmente ativas, com alterações compatíveis com infecção por HPV na colpocitologia e na colposcopia, verificando a distribuição das mulheres segundo o diagnóstico histopatológico de cervicite, NIC 1 e NIC 2 e 3, com relação a cor, escolaridade, estado conjugal, número de parceiros, idade ao início da atividade sexual, uso de anticoncepcional hormonal, paridade e idade. Investigou-se, também, a associação entre o hábito de fumar, as infecções vaginais, o pH vaginal, o tipo DNA viral diagnosticado pela captura de híbridos e os resultados da colpocitologia, com as lesões cervicais determinadas pela biópsia. É um estudo observacional de corte transversal, realizado com 100 mulheres de 20 a 35 anos de idade, atendidas no Serviço de Patologia Cervical do Hospital Maternidade "Leonor Mendes de Barros" e do "Centro de Atenção Integral à Saúde da Mulher". Para análise bivariada e múltipla utilizaram-se os métodos de Qui-quadrado, o teste exato de Fisher e a regressão logística, com limite de confiança de 95%. A prevalência de NIC 2 e 3 foi de 23%. Os grupos de cervicite, NIC 1 e NIC 2 e 3 foram semelhantes em relação a cor, escolaridade, estado conjugal, número de parceiros, idade ao início da atividade sexual, uso de anticoncepcional hormonal e paridade. O aumento da idade e o hábito de fumar estiveram significativamente associados com a gravidade da lesão cery ica I. A prevalência de Gardnerella vaginalis foi significativamente maior nas pacientes com NIC 2 e 3. O Mobiluncus sp, Trichomonas vaginalis e a Chlamydia trachomatis apresentaram uma distribuição semelhantes nos três grupos. Entretanto, a Candida sp apresentou uma tendência a ser mais freqüente nas pacientes com cervicite e NIC 1. Houve uma associação significativa entre NIC 2 e 3 e a detecção de DNA-HPV de alto risco oncológico. Concluímos que, nesta amostra de mulheres com alterações compatíveis com infecção por HPV na colpocitologia e colposcopia, a idade acima de 25 anos, o I hábito de fumar, a presença de Gardnerella vaginalis e a presença de HPV de alto risco oncológico, estiveram altamente associados com NIC 2 e 3Abstract: The target of this study was to evaluate the NIC 2 and 3 prevalence in sexually active women, with colpocitology and colposcopy showing changes compatible with HPV infection. It was verified the distribution of women according toe histopathologic diagnostic of cervicite, NIC 1 and NIC 2 and 3, with respect to color, schooling, marital status, number of sexual partners, age of first sexual intercourse, oral contraceptive use, parity and age. Also, It was investigated the relationship between smoking habit, vaginal infections, vaginal pH, viral DNA type diagnostic by hybrid capture.. and the colpocitology results, with the cervical lesions showed by biopsy. This is a cross sectional observation study carried out on 100 women, between 20 and 35 years of age, attended in the cervical pathology department of "Hospital Leonor Mendes de Barrosl" and "Centro qe Atenção Jntegral à Saúde da Mulher - CAISM." The data analysis was done with Chi-Square, Fisher test and logistical regression, with 95% confidence interval. he NIC 2 and 3 prevalence was 23%. The cervicite, NIC 1, NIC 2 and 3 groups' were similar in respect to color, schooling, marital status, number of sexual partners, age of first sexual intercourse, oral contraceptive use and parity. However, the increase in age and the smoking habit was significantly associated with the severity of cervical lesion. The Gardnerella vaginalis prevalence was significantly higher in patients with NIC 2 and 3. The Mobiluncus sp, Trichomonas vaginalis and Chllamydia trachomatis showed similar distribution in the three groups. However, the Candida sp showed a tendency to be more frequent in patients with cervicite and NIC 1. The association between NIC 2 and 3 and the detection of high risk DNA-HPV was significant. We concluded that, in this group of 100 women with changes in colpocitology I and colposcopy compatible with HPV infection, the age above 25, the smoking I habit, the presence of Gardnerella vaginalis and the presence of HPV of high oncological risk, was strongly associated with NIC 2 and 3MestradoTocoginecologiaMestre em Medicin

Uterine artery embolization for the treatment of symptomatic myomas in Brazilian women

CONTEXT: Uterine myomas are benign tumors that mostly occur in women of reproductive age at a frequency ranging from 20 to 25%. The symptoms are increased menstrual flow, pain and compressive signs. New treatments have been proposed and uterine artery embolization is one of them. OBJECTIVE: To evaluate the effects of treatment by embolization of the uterine artery, in women with symptomatic myomas. Uterine and dominant myoma volumes and the major symptoms were evaluated before treatment and 12 weeks later. TYPE OF STUDY: Open clinical trial. SETTING: A tertiary-care women's hospital. PARTICIPANTS: The study was conducted on 32 women with symptomatic single or multiple myomas of the uterine body, seen at the outpatient unit from May 2000 to September 2001. MAIN MEASUREMENTS: The patients were submitted to gynecological examination and abdominal and endovaginal pelvic ultrasonography, and the examinations were repeated 12 weeks after the first procedure. Uterine artery embolization using PVA (polyvinyl alcohol) particles of 355-700 µ was performed by catheterization of the right femoral artery in 30 women and by bilateral catheterization in two. RESULTS: Before embolization, the mean uterine volume of the 32 women was 455 cm³ and the mean volume of the dominant myoma was 150 cm³. Twelve weeks after embolization, the mean uterine volume was 256 cm³ and the mean volume of the dominant myoma was 91 cm³, with p < 0.01 in both cases. Twelve weeks after the treatment, all the women answered a questionnaire, which showed that 71% had improvement in menstrual regularity, 90% decreased menstrual volume and 81% shortened menstrual duration. The most frequent immediate post-procedure symptoms, established as complications, were pain (100%) and fatigue (34%). One woman had myoma degeneration and was submitted to myomectomy. CONCLUSION: The significant reduction in uterine and dominant myoma volume confirms the validity of the treatment of symptomatic myomas by the technique of uterine artery embolization in Brazilian women. There was significant reduction in menstrual flow and duration, as well as better cycle regularity in the women studied. The few adverse effects observed in the sample studied mainly involved pain immediately after embolization