Rosires Pereira de Andrade

Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial

BACKGROUND A randomised double-blind placebo-controlled phase II study was done to assess the efficacy of a prophylactic quadrivalent vaccine targeting the human papillomavirus (HPV) types associated with 70% of cervical cancers (types 16 and 18) and with 90% of genital warts (types 6 and 11). METHODS 277 young women (mean age 20.2 years [SD 1.7]) were randomly assigned to quadrivalent HPV (20 microg type 6, 40 microg type 11, 40 microg type 16, and 20 microg type 18) L1 virus-like-particle (VLP) vaccine and 275 (mean age 20.0 years [1.7]) to one of two placebo preparations at day 1, month 2, and month 6. For 36 months, participants underwent regular gynaecological examinations, cervicovaginal sampling for HPV DNA, testing for serum antibodies to HPV, and Pap testing. The primary endpoint was the combined incidence of infection with HPV 6, 11, 16, or 18, or cervical or external genital disease (ie, persistent HPV infection, HPV detection at the last recorded visit, cervical intraepithelial neoplasia, cervical cancer, or external genital lesions caused by the HPV types in the vaccine). Main analyses were done per protocol. FINDINGS Combined incidence of persistent infection or disease with HPV 6, 11, 16, or 18 fell by 90% (95% CI 71-97, p<0.0001) in those assigned vaccine compared with those assigned placebo. INTERPRETATION A vaccine targeting HPV types 6, 11, 16, 18 could substantially reduce the acquisition of infection and clinical disease caused by common HPV types.

High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up

Human papillomavirus (HPV) causes cervical, vulvar, and vaginal cancers, precancerous dysplasia, and genital warts. We report data for the longest efficacy evaluation to date of a prophylactic HPV vaccine. In total, 552 women (16–23 years) were enrolled in a randomised, placebo-controlled study of a quadrivalent HPV 6/11/16/18 L1 virus-like-particle vaccine with vaccination at months 0, 2, and 6. At regular intervals through 3 years, subjects underwent gynaecologic examination, cervicovaginal sampling for HPV DNA, serum anti-HPV testing, and Pap testing, with follow-up biopsy as indicated. A subset of 241 subjects underwent two further years of follow-up. At 5 years post enrolment, the combined incidence of HPV 6/11/16/18-related persistent infection or disease was reduced in vaccine-recipients by 96% (two cases vaccine versus 46 placebo). There were no cases of HPV 6/11/16/18-related precancerous cervical dysplasia or genital warts in vaccine recipients, and six cases in placebo recipients (efficacy=100%; 95% CI:12–100%). Through 5 years, vaccine-induced anti-HPV geometric mean titres remained at or above those following natural infection. In conclusion, a prophylactic quadrivalent HPV vaccine was effective through 5 years for prevention of persistent infection and disease caused by HPV 6/11/16/18. This duration supports vaccination of adolescents and young adults, which is expected to greatly reduce the burden of cervical and genital cancers, precancerous dysplasia, and genital warts.

Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16–26 years: a randomised, double-blind trial

BACKGROUND Primary analyses of a study in young women aged 16-26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years. METHODS We undertook this randomised, double-blind, efficacy, immunogenicity, and safety study of the 9vHPV vaccine study at 105 study sites in 18 countries. Women aged 16-26 years old who were healthy, with no history of abnormal cervical cytology, no previous abnormal cervical biopsy results, and no more than four lifetime sexual partners were randomly assigned (1:1) by central randomisation and block sizes of 2 and 2 to receive three intramuscular injections over 6 months of 9vHPV or qHPV (control) vaccine. All participants, study investigators, and study site personnel, laboratory staff, members of the sponsors study team, and members of the adjudication pathology panel were masked to vaccination groups. The primary outcomes were incidence of high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, invasive cervical carcinoma), vulvar disease (vulvar intraepithelial neoplasia grade 2/3, vulvar cancer), and vaginal disease (vaginal intraepithelial neoplasia grade 2/3, vaginal cancer) related to HPV 31, 33, 45, 52, and 58 and non-inferiority (excluding a decrease of 1·5 times) of anti-HPV 6, 11, 16, and 18 geometric mean titres (GMT). Tissue samples were adjudicated for histopathology diagnosis and tested for HPV DNA. Serum antibody responses were assessed by competitive Luminex immunoassay. The primary evaluation of efficacy was a superiority analysis in the per-protocol efficacy population, supportive efficacy was analysed in the modified intention-to-treat population, and the primary evaluation of immunogenicity was a non-inferiority analysis. The trial is registered with ClinicalTrials.gov, number NCT00543543. FINDINGS Between Sept 26, 2007, and Dec 18, 2009, we recruited and randomly assigned 14 215 participants to receive 9vHPV (n=7106) or qHPV (n=7109) vaccine. In the per-protocol population, the incidence of high-grade cervical, vulvar and vaginal disease related to HPV 31, 33, 45, 52, and 58 was 0·5 cases per 10 000 person-years in the 9vHPV and 19·0 cases per 10 000 person-years in the qHPV groups, representing 97·4% efficacy (95% CI 85·0-99·9). HPV 6, 11, 16, and 18 GMTs were non-inferior in the 9vHPV versus qHPV group from month 1 to 3 years after vaccination. No clinically meaningful differences in serious adverse events were noted between the study groups. 11 participants died during the study follow-up period (six in the 9vHPV vaccine group and five in the qHPV vaccine group); none of the deaths were considered vaccine-related. INTERPRETATION The 9vHPV vaccine prevents infection, cytological abnormalities, high-grade lesions, and cervical procedures related to HPV 31, 33, 45, 52, and 58. Both the 9vHPV vaccine and qHPV vaccine had a similar immunogenicity profile with respect to HPV 6, 11, 16, and 18. Vaccine efficacy was sustained for up to 6 years. The 9vHPV vaccine could potentially provide broader coverage and prevent 90% of cervical cancer cases worldwide. FUNDING Merck & Co, Inc.

Prevalência da infecção por Chlamydia Trachomatis e Neisseria Gonorrhoea em mulheres jovens sexualmente ativas em uma cidade do Sul do Brasil

PURPOSE to determine the prevalence of Chlamydia and gonorrhea in a sample of women from Curitiba. METHODS this was a cross-sectional study with a sample of sexually active non-pregnant women aged between 16 and 23 years-old, with an intact uterus, with up to four sexual partners, without evidence of fever or purulent cervicitis, submitted to pelvic examination and PCR-based urine- testing for Chlamydia and gonorrhea. Exclusion criteria included: vaccination for HPV, vaccination history for the past 21 days, previous abnormal cytology, history of genital warts, splenectomy, immune disorders, and use of immunosuppressive drugs. An interview regarding sociodemographic and obstetric data and gynecological risk behavior for sexual transmitted diseases was applied. For statistical analysis, we used the χ(2) or Fishers exact test to assess the association between variables. RESULTS the prevalence of Chlamydia and gonorrhea infection in the study group was 10.7 and 1.5%, respectively, and the rate of coinfection was 0.9%. No correlation was found between the age range of the volunteers, the onset of sexual activity, the number of sexual partners and of new sexual partners in the last six months, and the presence of Chlamydia or gonorrhea. In women who had vaginal discharge or ectropion, the prevalence of Chlamydia infection was two times higher than in those without such signs. CONCLUSIONS the results of this study were similar to national studies using PCR in urine samples for the detection of Chlamydia and gonorrhea in samples of non-pregnant women of the same age groups and with the same background. Since the volunteers with more than four sexual partners and those who had purulent endocervicitis were excluded, it is believed that the prevalence of Chlamydia and gonorrhea infection could have been greater in this population.

Características Demográficas e Intervalo para Atendimento em Mulheres Vítimas de Violência Sexual

Purpose: to investigate the social and demographic characteristics of women victims of sexual abuse; to evaluate their sexual experience before the abuse; to investigate the use of contraceptive methods at the time of the violence, and to observe the interval between the occurrence of the abuse and the search for a hospital attendance. Methods: 117 encoded records were evaluated, of a total of 134, obtained regarding the attendance of women victims of sexual abuse at the Maternity of the Hospital de Clinicas, in Curitiba, in the period between August, 1998 and June, 2000. Results: the age of the women varied from 5 to 49 years and half of them were young, with 19 years at the most. The majority of them were graduates or attending high school, 41 (41,0%) were students and 82 (82,0%) were single. The sexual experience analysis showed that one third (32,4%) was virgin. Among the women who reported sexual experience, 35 (47,9 %) were using a contraceptive method when they suffered abuse. There was a range from 2 hours to 2 months since the occurrence of the sexual violence until the search for attendance. Conclusions: the number of women victims of sexual abuse showed the importance of specialized attendance and also the necessity of a multidisciplinary attendance, since among the victims there are children who need special attention. The period of time between the sexual abuse and the search for hospital attendance was large, showing that there should be more information available to the population in relation to the prevention of unwanted pregnancy and sexually transmitted diseases, including HIV infection.

Morbidade e mortalidade neonatais relacionadas à idade materna igual ou superior a 35 anos, segundo a paridade

OBJETIVO: avaliar a morbidade e a mortalidade neonatais relacionadas a idade materna igual ou superior a 35 anos. METODOS: de 2.377 nascimentos em um ano, 316 (13,6%) eram de gestantes com idade igual ou superior a 35 anos. As gestantes selecionadas foram comparadas com mulheres entre 20 a 29 anos, randomicamente selecionadas entre 1170 delas (49,2%). Foram incluidas gestantes com idade gestacional acima de 22 semanas e recem nascido (RN) acima de 500 g. Foram excluidos 14 gemelares. Para avaliar a morbidade e a mortalidade foram consideradas as seguintes variaveis: indice de Apgar, peso ao nascer, malformacoes congenitas, adequacao do peso ao nascer e a mortalidade neonatal ate a alta hospitalar. RESULTADOS: quando avaliadas em conjunto nuliparas e multiparas, as gestantes com idade igual ou superior a 35 anos apresentaram uma proporcao significativamente maior de resultados perinatais desfavoraveis, o que nao se manteve quando foram excluidas as nuliparas. Multiparas com idade igual ou superior a 35 anos apresentaram maior proporcao de indice de Apgar baixo no 1o minuto: 21,3 e 13,1% (p = 0,015); RN pequeno para a idade gestacional: 15,2 e 6,7% (p < 0,02); RN grande para a idade gestacional: 5,7 e 0,0% (p < 0,02); baixo peso ao nascer: 23,8 e 14,5% (p < 0,01) e prematuridade: 16,7 e 6,7% (p < 0,005), respectivamente. Nao foram encontradas diferencas significativas para o indice Apgar baixo no 5o minuto, malformacoes congenitas, condicoes do recem-nascido no momento da alta hospitalar e mortalidade neonatal. CONCLUSOES: ocorreu um aumento da morbidade neonatal nas gestantes com idade igual ou superior a 35 anos, porem sem aumento da mortalidade neonatal.

Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women

Background A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. Methods Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16–26 years, and an immunogenicity and safety study in girls and boys aged 9–15 years. Participants (N=5312) received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs) were also monitored in all participants. Results The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6). Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99%) 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. Conclusions The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden.