RESUMO
BACKGROUND: Previous analyses from a randomized trial in women aged 24-45 have shown the quadrivalent HPV vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN) and external genital lesions (EGL) related to HPV 6/11/16/18 through 4 years. In this report we present long term follow-up data on the efficacy, safety and immunogenicity of the quadrivalent HPV vaccine in adult women. METHODS: Follow-up data are from a study being conducted in 5 sites in Colombia designed to evaluate the long-term immunogenicity, effectiveness, and safety of the qHPV vaccine in women who were vaccinated at 24 to 45 years of age (in the original vaccine group during the base study [nâ=â684]) or 29 to 50 years of age (in the original placebo group during the base study [nâ=â651]). This analysis summarizes data collected as of the year 6 post-vaccination visit relative to day 1 of the base study (median follow-up of 6.26 years) from both the original base study and the Colombian follow-up. RESULTS: There were no cases of HPV 6/11/16/18-related CIN or EGL during the extended follow-up phase in the per-protocol population. Immunogenicity persists against vaccine-related HPV types, and no evidence of HPV type replacement has been observed. No new serious adverse experiences have been reported. CONCLUSIONS: Vaccination with qHPV vaccine provides generally safe and effective protection from HPV 6-, 11-, 16-, and 18-related genital warts and cervical dysplasia through 6 years following administration to 24-45 year-old women. TRIAL REGISTRATION: Clinicaltrials.govNCT00090220.
Assuntos
Vacinas contra Papillomavirus/uso terapêutico , Adulto , Colômbia , Condiloma Acuminado/prevenção & controle , Método Duplo-Cego , Feminino , Seguimentos , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Papillomavirus Humano 11/imunologia , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Papillomavirus Humano 6/imunologia , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/efeitos adversos , Vacinas contra Papillomavirus/imunologia , Gravidez , Segurança , Resultado do Tratamento , Neoplasias do Colo do Útero/prevenção & controle , Adulto Jovem , Displasia do Colo do Útero/prevenção & controleRESUMO
BACKGROUND: We assessed if risk of developing cervical intraepithelial neoplasia grade 2/3 (CIN2/3) or adenocarcinoma in situ (AIS) is associated with a short interval between menarche and first sexual intercourse (FSI). METHODS: A total of 1009 Colombian and 1012 Finnish females, aged 16-23, who were enrolled in the phase 3 trials of a quadrivalent human papillomavirus (HPV) 6/11/16/18 vaccine had nonmissing data for age of menarche and FSI. The impact of menarche interval on the odds of developing CIN2-3/AIS was evaluated in placebo recipients who were DNA negative to HPV 6/11/16/18/31/33/35/39/45/51/52/56/58/59 and seronegative to HPV 6/11/16/18 at day 1, and had a normal Pap result at day 1 and month 7, thus approximating sexually naive adolescents (n = 504). RESULTS: The mean age of menarche and FSI was 12.4 and 16.0 years, respectively. Among the women approximating sexually naive adolescents, 18 developed CIN2-3/AIS. Compared with women who postponed FSI beyond 3 years of menarche, those with FSI within 3 years of menarche had a greater risk of cytologic abnormalities (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.02-2.68; P = .04) and CIN2-3/AIS (OR, 3.56; 95% CI, 1.02-12.47; P = .05). CONCLUSIONS: A short interval between menarche and FSI was a risk factor for cytologic abnormalities and high-grade cervical disease. These data emphasize the importance of primary prevention through education and vaccination. CLINICAL TRIALS REGISTRATION: NCT00092521 and NCT00092534.
Assuntos
Coito , Menarca , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Comportamento Sexual , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/virologia , Adolescente , Adulto , Ensaios Clínicos Fase III como Assunto , Colômbia/epidemiologia , Feminino , Finlândia/epidemiologia , Humanos , Medição de Risco , Fatores de Tempo , Adulto Jovem , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/virologiaRESUMO
BACKGROUND: Prophylactic vaccination with a quadrivalent HPV (types 6, 11, 16, 18) vaccine (qHPV) has been shown to prevent infection with HPV 6/11/16/18 and associated disease in women and more recently, in men. Here we report on the safety and reactogenicity of the qHPV vaccine in males. A total of 4,065 healthy males aged 16-26 years were enrolled into a randomized, placebo-controlled, double-blind trial. Subjects were randomized 1:1 to receive qHPV vaccine or placebo at day 1, month 2, and month 6. Safety and tolerability were assessed via the collection of reported adverse experiences (AEs). All serious AEs (vaccine- or procedure-related or not) and all deaths occurring during the study were recorded. Safety analyses were conducted in all subjects who received at least one dose of vaccine or placebo. The proportion of subjects who reported at least one injection-site AE was higher in the qHPV vaccine group versus the placebo group (60.1% vs 53.7%, respectively), however most of these AEs were mild/moderate in intensity. The incidence of at least one systemic AE was comparable between the vaccine and placebo groups (31.7% vs 31.4%, respectively). There were no vaccine-related serious AEs or deaths. The occurrence of AEs did not increase with each successive injection, and among trial participants who were seropositive for at least one vaccine HPV type at enrollment, the profile of adverse events was similar to that of the entire study cohort. The qHPV vaccine was generally well tolerated in males aged 16-26 years and had a favorable safety profile.
Assuntos
Vacinas contra Papillomavirus , Vacinação/efeitos adversos , Adolescente , Adulto , Método Duplo-Cego , Feminino , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Papillomavirus Humano 11/imunologia , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Papillomavirus Humano 6/imunologia , Humanos , Masculino , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/efeitos adversos , Vacinas contra Papillomavirus/imunologia , Segurança , Adulto JovemRESUMO
BACKGROUND: The impact of the prophylactic vaccine against human papillomavirus (HPV) types 6, 11, 16, and 18 (HPV6/11/16/18) on all HPV-associated genital disease was investigated in a population that approximates sexually naive women in that they were "negative to 14 HPV types" and in a mixed population of HPV-exposed and -unexposed women (intention-to-treat group). METHODS: This analysis studied 17 622 women aged 15-26 years who were enrolled in one of two randomized, placebo-controlled, efficacy trials for the HPV6/11/16/18 vaccine (first patient on December 28, 2001, and studies completed July 31, 2007). Vaccine or placebo was given at day 1, month 2, and month 6. All women underwent cervicovaginal sampling and Papanicolaou (Pap) testing at day 1 and every 6-12 months thereafter. Outcomes were any cervical intraepithelial neoplasia; any external anogenital and vaginal lesions; Pap test abnormalities; and procedures such as colposcopy and definitive therapy. Absolute rates are expressed as women with endpoint per 100 person-years at risk. RESULTS: The average follow-up was 3.6 years (maximum of 4.9 years). In the population that was negative to 14 HPV types, vaccination was up to 100% effective in reducing the risk of HPV16/18-related high-grade cervical, vulvar, and vaginal lesions and of HPV6/11-related genital warts. In the intention-to-treat group, vaccination also statistically significantly reduced the risk of any high-grade cervical lesions (19.0% reduction; rate vaccine = 1.43, rate placebo = 1.76, difference = 0.33, 95% confidence interval [CI] = 0.13 to 0.54), vulvar and vaginal lesions (50.7% reduction; rate vaccine = 0.10, rate placebo = 0.20, difference = 0.10, 95% CI = 0.04 to 0.16), genital warts (62.0% reduction; rate vaccine = 0.44, rate placebo = 1.17, difference = 0.72, 95% CI = 0.58 to 0.87), Pap abnormalities (11.3% reduction; rate vaccine = 10.36, rate placebo = 11.68, difference = 1.32, 95% CI = 0.74 to 1.90), and cervical definitive therapy (23.0% reduction; rate vaccine = 1.97, rate placebo = 2.56, difference = 0.59, 95% CI = 0.35 to 0.83), irrespective of causal HPV type. CONCLUSIONS: High-coverage HPV vaccination programs among adolescents and young women may result in a rapid reduction of genital warts, cervical cytological abnormalities, and diagnostic and therapeutic procedures. In the longer term, substantial reductions in the rates of cervical, vulvar, and vaginal cancers may follow.
Assuntos
Alphapapillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/farmacologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Infecções Tumorais por Vírus/prevenção & controle , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Feminino , Doenças dos Genitais Femininos/prevenção & controle , Doenças dos Genitais Femininos/virologia , Saúde Global , Papillomavirus Humano 11/imunologia , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Papillomavirus Humano 6/imunologia , Humanos , Estimativa de Kaplan-Meier , Teste de Papanicolaou , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/virologia , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/virologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adulto Jovem , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/virologiaRESUMO
BACKGROUND AND AIMS: Recognition of human papillomavirus (HPV) as a necessary cause of cervical cancer (CC) led to new perspectives for its control and the demonstration of an effective primary prevention strategy through vaccination. We undertook this study to evaluate the safety, efficacy and immunogenicity of a quadrivalent HPV6/11/16/18 vaccine in Mexican women. METHODS: A total of 679 Mexican women between 18 and 23 years old participated in two Phase III double-blind, randomized, placebo-controlled clinical trials of a quadrivalent HPV 6/11/16/18 vaccine. Women were enrolled who tested negative for pregnancy and reported having four or less sexual partners during their lifetime. Vaccine or placebo was administered at day 1, month 2 and month 6. RESULTS: Among Mexican women who were naïve to the respective vaccine type at enrollment, the quadrivalent vaccine was highly efficacious, preventing 100% of HPV6/11/16/18-related cervical intraepithelial neoplasia grade 2/3, adenocarcinoma in situ, condyloma and vaginal intraepithelial neoplasia. Statistical significance was not reached for every endpoint due to the limited sample size. Vaccination was generally well tolerated and immunogenic. DISCUSSION: To widely administer the vaccine, collaborative efforts should be coordinated among public, private and local community sectors. In light of the scarce knowledge of many health professionals with respect to the primary prevention of CC, it will be necessary to educate health providers on the advantages and specific recommendations of HPV vaccines and secondary prevention. Decision making should be based on scientific evidence, allowing health professionals to provide an organized social response that supports the universal right to health.
Assuntos
Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Adenocarcinoma/prevenção & controle , Adolescente , Método Duplo-Cego , Feminino , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Humanos , México , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/imunologia , Saúde Pública , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Adulto Jovem , Displasia do Colo do Útero/prevenção & controleRESUMO
BACKGROUND: Although the peak incidence of human papillomavirus (HPV) infection occurs in most populations within 5-10 years of first sexual experience, all women remain at risk for acquisition of HPV infections. We tested the safety, immunogenicity, and efficacy of the quadrivalent HPV (types 6, 11, 16, 18) L1 virus-like-particle vaccine in women aged 24-45 years. METHODS: Women aged 24-45 years with no history of genital warts or cervical disease were enrolled from community health centres, academic health centres, and primary health-care providers into an ongoing multicentre, parallel, randomised, placebo-controlled, double-blind study. Participants were allocated by computer-generated schedule to receive quadrivalent HPV vaccine (n=1911) or placebo (n=1908) at day 1, and months 2 and 6. All study site investigators and personnel, study participants, monitors, and central laboratory personnel were blinded to treatment allocation. Coprimary efficacy endpoints were 6 months' or more duration of infection and cervical and external genital disease due to HPV 6, 11, 16, 18; and due to HPV 16 and 18 alone. Primary efficacy analyses were done in a per-protocol population, but intention-to-treat analyses were also undertaken. This study is registered with ClinicalTrials.gov, number NCT00090220. FINDINGS: 1910 women received at least one dose of vaccine and 1907 at least one dose of placebo. In the per-protocol population, efficacy against the first coprimary endpoint (disease or infection related to HPV 6, 11, 16, and 18) was 90.5% (95% CI 73.7-97.5, four of 1615 cases in the vaccine group vs 41/1607 in the placebo group) and 83.1% (50.6-95.8, four of 1601 cases vs 23/1579 cases) against the second coprimary endpoint (disease or infection related to HPV 16 and 18 alone). In the intention-to-treat population, efficacy against the first coprimary endpoint was 30.9% (95% CI 11.1-46.5, 108/1886 cases vs 154/1883 cases) and against the second coprimary endpoint was 22.6% (-2.9 to 41.9, 90/1886 cases vs 115/1883 cases), since infection and disease were present at baseline. We recorded no vaccine-related serious adverse events. INTERPRETATION: The quadrivalent HPV vaccine is efficacious in women aged 24-45 years not infected with the relevant HPV types at enrolment. FUNDING: Merck (USA).
Assuntos
Alphapapillomavirus , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Segurança , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Fatores Etários , Colômbia/epidemiologia , Método Duplo-Cego , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18 , Humanos , Incidência , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas contra Papillomavirus/efeitos adversos , Filipinas/epidemiologia , Tailândia/epidemiologia , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Vacinação/efeitos adversos , Vacinação/métodosRESUMO
OBJECTIVE: The purpose of this study was to inform policy regarding human papillomavirus (HPV) vaccination in North America. We measured the clinical impact of HPV-6/-11/-16/-18 vaccination in North American women. STUDY DESIGN: The study enrolled 21,954 women, the majority aged 16-25, across 5 studies of a quadrivalent HPV vaccine or its HPV-16 vaccine prototype. The North American subjects (n = 5996) were pooled from these trials, and the prevalence of HPV-6/-11/-16/-18 exposure was measured. The impact of vaccination on the burden of anogenital HPV lesions in an intention-to-treat population (regardless of enrollment HPV status) was calculated. RESULTS: At enrollment, the median age was 20 years; 13% of the women had had a Papanicolaou test abnormality, and 76% of the women had negative tests results for all 4 vaccine HPV types. With approximately 3 years of follow-up evaluations in the intention-to-treat population (regardless of enrollment HPV status), vaccination reduced the rate of HPV-16- and -18-related precancers and HPV-6/-11/-16/-18-related genital lesions by 66.4% (95% CI, 42.7%-81.1%) and 57.7% (95% CI, 27.3%-76.3%), respectively. CONCLUSION: The administration of HPV vaccine to sexually active North American women reduced the burden of HPV-6/-11/-16/-18-related disease. Catch-up vaccination programs in this population are warranted.