RESUMEN

Background: COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the prevalence and the risk factors for preeclampsia in hospitalized pregnant women with COVID-19. As well as comparing maternal and perinatal outcomes in hospitalized pregnant women with COVID-19 and preeclampsia with those without preeclampsia. Methods: Prospective cohort study of 100 hospitalized pregnant women from two tertiary hospitals, diagnosed with COVID-19, and divided into two groups: PE+ group (pregnant women with COVID-19 and preeclampsia) and PE- group (pregnant women with COVID-19 without preeclampsia). These pregnant women had prevalence, risk factors, maternal and perinatal data analyzed. Results: The prevalence of preeclampsia was 11%. Severe COVID-19 was the main risk factor for preeclampsia (OR = 8.18 [CI 1.53-43.52]), as well as fetal growth restriction was the main perinatal outcome (OR = 8.90 [CI 1.52-38.4]). Comorbidities were more frequent in the PE+ group (63.6% vs 31.5%, p = 0.03), as well as prematurity (81.8% vs 41.6%, p = 0.02), low birth weight (63.6% vs 24.7%, p = 0.01), and the need for neonatal intensive care admission of the newborn (63.6% vs 27.0%, p = 0.03). Pregnant women with PE had twice as long a length of stay in the intensive care unit (RR = 2.35 [CI 1.34-4.14]). Although maternal mortality was more frequent among pregnant women with PE, it was not statistically significant. Conclusions: Prevalence of preeclampsia in hospitalized pregnant women with COVID-19 was 11%. Severe COVID-19 was the main risk factor for preeclampsia and associated comorbidities increased the risk for developing preeclampsia. Long length of stay in the intensive care unit was the main maternal outcome and fetal growth restriction was the main perinatal outcome of preeclampsia.

Asunto(s)

COVID-19 , Preeclampsia , Complicaciones Infecciosas del Embarazo , Resultado del Embarazo , SARS-CoV-2 , Centros de Atención Terciaria , Humanos , Embarazo , Femenino , Preeclampsia/epidemiología , COVID-19/epidemiología , COVID-19/mortalidad , Brasil/epidemiología , Estudios Prospectivos , Adulto , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/virología , Factores de Riesgo , Resultado del Embarazo/epidemiología , Prevalencia , Recién Nacido , Retardo del Crecimiento Fetal/epidemiología , Retardo del Crecimiento Fetal/virología , Comorbilidad

RESUMEN

OBJECTIVE: To compare the diagnosis of bacterial vaginosis (BV) by Nugent scoring criteria (Nugent-BV) and the diagnosis of BV and/or aerobic vaginitis (AV) using Donders criteria (Donders-BV/AV) for identifying Molecular-BV detected by bacterial 16s rRNA profiling. METHODS: We enrolled 512 women of reproductive age in Brazil with data available on Nugent and Donders microscopic analysis and 16S rRNA sequencing. We constructed receiver operating characteristic (ROC) curves of Nugent-BV and Donders-BV/AV and calculated their area under the curves (AUCs) and 95% confidence interval (CI) for matching Molecular-BV. RESULTS: A total of 155 (28.7%) participants were positive for Nugent-BV. Donders-BV and -AV were detected in 90 (17.6%) and 75 (14.6%) participants, respectively, while 28 (5.5%) had concurrent Donders-BV and -AV. Molecular-BV was identified in 139 (27.1%) participants. Analysis of ROC curves showed that diagnosis of Nugent-BV more accurately aligned with presence of Molecular-BV (AUC: 0.88, 95% CI: 0.84-0.91) when compared to Donders-AV/BV (AUC: 0.84; CI: 0.80-0.87) (P = 0.005). CONCLUSION: The use of Nugent-BV is more representative of Molecular-BV than Donders-AV/BV.

Asunto(s)

Microbiota , Vaginitis , Vaginosis Bacteriana , Femenino , Humanos , Microbiota/genética , ARN Ribosómico 16S/genética , Vagina/microbiología , Vaginitis/diagnóstico , Vaginosis Bacteriana/diagnóstico , Vaginosis Bacteriana/microbiología

RESUMEN

BACKGROUND: Global variation in human papillomavirus (HPV) prevalence and persistence may be explained by differences in risk factors, such as sexual activity, oral contraceptive use, and behavioral factors. We evaluated determinants of acquisition and clearance of HPV infection among young women previously unexposed to HPV. METHODS: Five hundred thirty-four women aged 15 to 25 years who were cytology and HPV DNA negative, and seronegative for anti-HPV-16/18 antibodies, were recruited (July 2000-September 2001) from study centers in Brazil, the United States, and Canada (NCT00689741/NCT00120848). They were followed up for 76 months. Cervical samples were HPV genotyped via polymerase chain reaction. We used multivariable (forward stepwise, P = 0.15) Cox proportional hazards regression to estimate rate ratios (RR) and 95% confidence intervals (CI), separately according to length of follow-up time. RESULTS: On short-term follow-up (0-27 months), 257 (48%; 8535.80 person-months; incidence rate = 30.11; 95% CI, 26.64-34.02) incident HPV infections were detected. Marital status, lifetime number of sex partners, history of any sexually transmitted disease, and occasional use of oral contraceptives were strongly associated with acquisition of any HPV. Having 2 or more lifetime sex partners (RR, 2.03; 95% CI, 1.37-3.02) and a history of any sexually transmitted disease (RR, 1.98; 95% CI, 1.19-3.29) were the most important determinants of high-risk HPV (hrHPV) incidence. During the entire follow-up (0-76 months), an increased hrHPV clearance was found among women in North America (RR, 1.38; 95% CI, 1.08-1.78) and black women (RR, 1.64; 95% CI, 1.04-2.60). Greater number of lifetime partners was associated with reduced clearance rates for any HPV (RR, 0.65; 95% CI, 0.43-0.98). CONCLUSIONS: We identified variation in risk of HPV acquisition and clearance among women unexposed to HPV at baseline.

Asunto(s)

Cuello del Útero/virología , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Adolescente , Adulto , Brasil , Canadá , Estudios de Cohortes , Método Doble Ciego , Femenino , Genotipo , Humanos , Incidencia , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , Prevalencia , Factores de Riesgo , Conducta Sexual/estadística & datos numéricos , Parejas Sexuales , Estados Unidos , Adulto Joven

RESUMEN

OBJECTIVE: The present study aimed to evaluate the association between altered methylation and histologically confirmed high grade cervical intraepithelial neoplasia (hgCIN). METHODS: Methylation levels in selected host (CADM1, MAL, DAPK1) and HPV (L1_I, L1_II, L2) genes were measured by pyrosequencing in DNA samples obtained from 543 women recruited in Curitiba (Brazil), 249 with hgCIN and 294 without cervical lesions. Association of methylation status with hgCIN was estimated by Odds Ratio (OR) with 95% confidence interval (CI). RESULTS: The mean methylation level increased with severity of the lesion in the host and viral genes (p-trend < 0.05), with the exception of L1_II region (p-trend = 0.075). Positive association was found between methylation levels for host genes and CIN2 and CIN3 lesions respectively [CADM1: OR 4.17 (95%CI 2.03-8.56) and OR 9.54 (95%CI 4.80-18.97); MAL: OR 5.98 (95%CI 2.26-15.78) and OR 22.66 (95%CI 9.21-55.76); DAPK1: OR 3.37 (95%CI 0.93-12.13) and OR 6.74 (95%CI 1.92-23.64)]. Stronger risk estimates were found for viral genes [L1_I: OR 10.74 (95%CI 2.66-43.31) and OR 15.00 (95%CI 3.00-74.98); L1_II: OR 73.18 (95%CI 4.07-1315.94) and OR 32.50 (95%CI 3.86-273.65); L2: OR 4.73 (95%CI 1.55-14.44) and OR 10.62 (95%CI 2.60-43.39)]. The cumulative effect of the increasing number of host and viral methylated genes was associated with the risk of CIN2 and CIN3 lesions (p-trend < 0.001). CONCLUSIONS: Our results, empowered by a wide cervical sample series with a large number of hgCIN, supported the role of methylation as marker of aggressiveness.

Asunto(s)

Metilación de ADN , Papillomaviridae/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/virología , Adulto , Estudios de Casos y Controles , Molécula 1 de Adhesión Celular/genética , Proteínas Quinasas Asociadas a Muerte Celular/genética , Femenino , Humanos , Proteínas Proteolipídicas Asociadas a Mielina y Linfocito/genética , Clasificación del Tumor , Infecciones por Papillomavirus/genética , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/patología

RESUMEN

Human T-cell lymphotropic virus types 1/2 (HTLV-1/2) are transmitted through sexual intercourse, transfusion of blood components, and vertical transmission, predominantly through breastfeeding. Six hundred forty-three pregnant women from a high-risk prenatal care unit at a general hospital were tested by serological tests using chemiluminescence (CMIA) for screening, followed by a molecular confirmatory test. Four patients (0.6%) tested positive for HTLV-1/2 by CMIA, two samples (0.3%) for each patient were confirmed as having HTLV-1 or HTLV-2 by PCR. The results show the importance of inclusion of HTLV-1/2 screening for pregnant women in high-risk prenatal care and the need for a molecular biological method to confirm HTLV-1/2 infection.

Asunto(s)

Infecciones por HTLV-I/diagnóstico , Infecciones por HTLV-II/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Reacción en Cadena de la Polimerasa/métodos , Complicaciones Infecciosas del Embarazo/diagnóstico , Adolescente , Adulto , Estudios Transversales , Femenino , Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-II/epidemiología , Humanos , Tamizaje Masivo/métodos , Persona de Mediana Edad , Embarazo , Prevalencia , Pruebas Serológicas/métodos , Adulto Joven

RESUMEN

Cervical cancer is an important health issue in Latin America. Although HPV infections can have spontaneous clearance, persistence of high-risk (HR) HPV is a risk factor for cervical cancer among women and it is even higher in HIV-infected women. To determine the prevalence of HR-HPV and risk factors among HIV-infected women attending reference services for HIV/AIDS in different regions of Brazil. Cross-sectional study conducted among HIV-infected women attended at referral care centers for HIV/AIDS in nine states of Brazil. Women from 18 to 49 years that accept to participate and were not pregnant at the time of the approach were recruited for the study. The HPV screening was realized using qPCR in closed system, in vitro Diagnostic, COBAS® -HPV Roche. The cytology results were available by the Bethesda System. A total of 802(89.1%) from the selected women agreed to participate in the study. Median age was 39(Inter quartile range [IQR34-46]) years and median education was 9(IQR6-11) years. General prevalence of HR-HPV was 28.4%(228/802). HPV-16 prevalence rate was 8.1%(65/802), HPV-18 was 3.7%(30/802) and other types of HR-HPV were 23.6% (189/802). Risk factors for HR-HPV infection in the multivariate logistic regression analysis were: age ranging from 18 to 34 years (OR = 1.43[95%CI:1.18-1.75]), illicit drugs use (OR = 1.61[95%CI:1.10-2.42]) and abnormal cervical cytology (OR = 1.56[95%CI:1.34-1.81]). Results showed a prevalence rate of 28.4% of HR-HPV infection in women living with HIV in Brazil. These infections were significantly associated with having less than 35 years old, illicit drug use and abnormal cervical cytology.

Asunto(s)

Coinfección , Infecciones por VIH/complicaciones , Infecciones por Papillomavirus/complicaciones , Adulto , Brasil/epidemiología , Estudios Transversales , Femenino , Genotipo , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , VIH-1/fisiología , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 16/fisiología , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/aislamiento & purificación , Papillomavirus Humano 18/fisiología , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Embarazo , Prevalencia , Factores de Riesgo , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/virología , Adulto Joven

RESUMEN

Background: Current HPV vaccines do not protect against all oncogenic HPV types. Following vaccination, type replacement may occur, especially if different HPV types competitively interact during natural infection. Because of their common route of transmission, it is difficult to assess type interactions in observational studies. Our aim was to evaluate type replacement in the setting of HPV vaccine randomized controlled trials (RCTs). Methods: Data were pooled from the Costa Rica Vaccine Trial (CVT; NCT00128661) and PATRICIA trial (NCT001226810)-two large-scale, double-blind RCTs of the HPV-16/18 AS04-adjuvanted vaccine-to compare cumulative incidence of nonprotected HPV infections across trial arms after four years. Negative rate difference estimates (rate in control minus vaccine arm) were interpreted as evidence of replacement if the associated 95% confidence interval excluded zero. All statistical tests were two-sided. Results: After applying relevant exclusion criteria, 21 596 women were included in our analysis (HPV arm = 10 750; control arm = 10 846). Incidence rates (per 1000 infection-years) were lower in the HPV arm than in the control arm for grouped nonprotected oncogenic types (rate difference = 1.6, 95% confidence interval [CI] = 0.9 to 2.3) and oncogenic/nononcogenic types (rate difference = 0.2, 95% CI = -0.3 to 0.7). Focusing on individual HPV types separately, no deleterious effect was observed. In contrast, a statistically significant protective effect (positive rate difference and 95% CI excluded zero) was observed against oncogenic HPV types 35, 52, 58, and 68/73, as well as nononcogenic types 6 and 70. Conclusion: HPV type replacement does not occur among vaccinated individuals within four years and is unlikely to occur in vaccinated populations.

Asunto(s)

Papillomavirus Humano 16/inmunología , Papillomavirus Humano 18/inmunología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/uso terapéutico , Displasia del Cuello del Útero/prevención & control , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Adulto , Costa Rica , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/virología , Vacunas contra Papillomavirus/inmunología , Resultado del Tratamiento , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/virología , Vacunación/métodos , Adulto Joven , Displasia del Cuello del Útero/inmunología , Displasia del Cuello del Útero/virología

RESUMEN

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 <21 years (RR=1.33, 95% CI 1.1 to 1.7) and women having >1 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. TRIAL REGISTRATION NUMBER: NCT00689741, NCT00120848; Post-results.

Asunto(s)

Papillomaviridae/genética , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Adolescente , Adulto , ADN Viral/análisis , Método Doble Ciego , Femenino , Humanos , Incidencia , Papillomaviridae/aislamiento & purificación , Factores de Riesgo , Parejas Sexuales , Factores de Tiempo , Neoplasias del Cuello Uterino/prevención & control , Adulto Joven

RESUMEN

We evaluated the efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in preventing HPV-related disease after surgery for cervical lesions in a post-hoc analysis of the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681). Healthy women aged 15-25 years were randomized (1:1) to receive vaccine or control at months 0, 1 and 6 and followed for 4 years. Women were enrolled regardless of their baseline HPV DNA status, HPV-16/18 serostatus, or cytology, but excluded if they had previous or planned colposcopy. The primary and secondary endpoints of PATRICIA have been reported previously; the present post-hoc analysis evaluated efficacy in a subset of women who underwent an excisional procedure for cervical lesions after vaccination. The main outcome was the incidence of subsequent HPV-related cervical intraepithelial neoplasia grade 2 or greater (CIN2+) 60 days or more post-surgery. Other outcomes included the incidence of HPV-related CIN1+, and vulvar or vaginal intraepithelial neoplasia (VIN/VaIN) 60 days or more post-surgery. Of the total vaccinated cohort of 18,644 women (vaccine = 9,319; control = 9,325), 454 (vaccine = 190, control = 264) underwent an excisional procedure during the trial. Efficacy 60 days or more post-surgery for a first lesion, irrespective of HPV DNA results, was 88.2% (95% CI: 14.8, 99.7) against CIN2+ and 42.6% (-21.1, 74.1) against CIN1+. No VIN was reported and one woman in each group had VaIN2+ 60 days or more post-surgery. Women who undergo surgical therapy for cervical lesions after vaccination with the HPV-16/18 vaccine may continue to benefit from vaccination, with a reduced risk of developing subsequent CIN2+.

Asunto(s)

Adyuvantes Inmunológicos , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 18/inmunología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/inmunología , Displasia del Cuello del Útero/etiología , Displasia del Cuello del Útero/patología , Adolescente , Adulto , Femenino , Humanos , Clasificación del Tumor , Recurrencia Local de Neoplasia , Evaluación de Resultado en la Atención de Salud , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Vacunación , Adulto Joven , Displasia del Cuello del Útero/cirugía

RESUMEN

HPV-023 (NCT00518336; ClinicalTrial.gov) is a long-term follow-up of an initial double-blind, randomized (1:1), placebo-controlled study (HPV-001, NCT00689741) evaluating the efficacy against human papillomavirus (HPV)-16/18 infection and associated cyto-histopathological abnormalities, persistence of immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine. Among the women, aged 15-25 years, enrolled in HPV-001 and who participated in the follow-up study HPV-007 (NCT00120848), a subset of 437 women from five Brazilian centers participated in this 36-month long-term follow-up (HPV-023) for a total of 113 months (9.4 years). During HPV-023, anti-HPV-16/18 antibodies were measured annually by enzyme-linked immunosorbent assay (ELISA) and pseudovirion-based neutralisation assay (PBNA). Cervical samples were tested for HPV DNA every 6 months, and cyto-pathological examinations were performed annually. During HPV-023, no new HPV-16/18-associated infections and cyto-histopathological abnormalities occurred in the vaccine group. Vaccine efficacy (VE) against HPV-16/18 incident infection was 100% (95%CI: 66.1, 100). Over the 113 months (9.4 years), VE was 95.6% (86.2, 99.1; 3/50 cases in vaccine and placebo groups, respectively) against incident infection, 100% (84·1, 100; 0/21) against 6-month persistent infection (PI); 100% (61·4, 100; 0/10) against 12-month PI; 97·1% (82.5, 99.9; 1/30) against ≥ ASC-US; 95·0% (68.0, 99.9; 1/18) against ≥ LSIL; 100% (45.2, 100; 0/8) against CIN1+; and 100% (-128.1, 100; 0/3) against CIN2+ associated with HPV-16/18. All vaccinees remained seropositive to HPV-16/18, with antibody titers remaining several folds above natural infection levels, as measured by ELISA and PBNA. There were no safety concerns. To date, these data represent the longest follow-up reported for a licensed HPV vaccine.

Asunto(s)

Papillomavirus Humano 16/inmunología , Papillomavirus Humano 18/inmunología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/efectos adversos , Vacunas contra Papillomavirus/inmunología , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Brasil , ADN Viral/análisis , ADN Viral/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Histocitoquímica , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Humanos , Pruebas de Neutralización , Vacunas contra Papillomavirus/administración & dosificación , Resultado del Tratamiento , Frotis Vaginal , Adulto Joven

RESUMEN

BACKGROUND: We examined risk of newly detected human papillomavirus (HPV) infection and cervical abnormalities in relation to HPV type 16/18 antibody levels at enrollment in PATRICIA (Papilloma Trial Against Cancer in Young Adults; NCT00122681). METHODS: Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative vs seropositive women (15-25 years) in the control arm (DNA negative at baseline for the corresponding HPV type [HPV-16: n = 8193; HPV-18: n = 8463]). RESULTS: High titers of naturally acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASCUS+), and cervical intraepithelial neoplasia grades 1/2 or greater (CIN1+, CIN2+). For HPV-18, although seropositivity was associated with lower risk of ASCUS+ and CIN1+, no association between naturally acquired antibodies and infection was demonstrated. Naturally acquired HPV-16 antibody levels of 371 (95% confidence interval [CI], 242-794), 204 (95% CI, 129-480), and 480 (95% CI, 250-5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASCUS+, respectively. CONCLUSIONS: Naturally acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type.

Asunto(s)

Anticuerpos Antivirales/inmunología , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 18/inmunología , Papillomaviridae/inmunología , Infecciones por Papillomavirus/diagnóstico , Adolescente , Adulto , ADN Viral/genética , Método Doble Ciego , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/virología , Factores de Riesgo , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/virología

RESUMEN

BACKGROUND: More information is needed about time between sexual initiation and human papillomavirus (HPV) infection and development of cervical precancer. METHODS: The objectives were to investigate the time between first sexual activity and detection of first cervical HPV infection or development of first cervical intraepithelial neoplasia (CIN), and associated factors in women from the double-blind, multinational, 4-year PATRICIA trial. PATRICIA enroled women aged 15-25 years with no more than 6 lifetime sexual partners. Women were randomized 1:1 to the HPV-16/18 AS04-adjuvanted vaccine or to control, but only women from the control arm who began sexual intercourse during the study or within 6 months before enrolment, and had no HPV infection detected before the recorded date of their first sexual intercourse, were included in the present analysis. The time between onset of sexual activity and detection of the first cervical HPV infection or development of the first CIN lesion was analyzed using Kaplan-Meier and univariate and multivariable Cox proportional-hazards models. RESULTS: A total of 9337 women were enroled in the control arm of PATRICIA of whom 982 fulfilled the required inclusion criteria for analysis. A cumulative total of 28%, 44%, and 62% of the subjects had HPV infection within 12, 24, and 48 months, respectively. The overall incidence rate was 27.08 per 100 person-years. The most common oncogenic types associated with 6-month persistent infection were HPV-16 (incidence rate: 2.74 per 100 person-years), HPV-51 (2.70), HPV-52 (1.66), HPV-66 (1.14), and HPV-18 (1.09). Increased infection risk was associated with more lifetime sexual partners, being single, Chlamydia trachomatis history, and duration of hormone use. CIN1+ and CIN2+ lesions were most commonly associated with HPV-16, with an overall incidence rate of 1.87 and 1.07 per 100 person-years, respectively. Previous cervical HPV infection was most strongly associated with CIN development. CONCLUSIONS: More than 25% of women were infected with HPV within 1 year of beginning sexual activity. Without underestimating the value of vaccination at older ages, our findings emphasize its importance before sexual initiation. TRIAL REGISTRATION: clinicaltrials.gov: NCT00122681 .

Asunto(s)

Infecciones por Papillomavirus/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Conducta Sexual/estadística & datos numéricos , Displasia del Cuello del Útero/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Adolescente , Adulto , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Factores de Riesgo , Parejas Sexuales , España/epidemiología , Factores de Tiempo , Adulto Joven

RESUMEN

BACKGROUND: The control arm of PATRICIA (PApilloma TRIal against Cancer In young Adults, NCT00122681) was used to investigate the risk of progression from cervical HPV infection to cervical intraepithelial neoplasia (CIN) or clearance of infection, and associated determinants. METHODS AND FINDINGS: Women aged 15-25 years were enrolled. A 6-month persistent HPV infection (6MPI) was defined as detection of the same HPV type at two consecutive evaluations over 6 months and clearance as ≥2 type-specific HPV negative samples taken at two consecutive intervals of approximately 6 months following a positive sample. The primary endpoint was CIN grade 2 or greater (CIN2+) associated with the same HPV type as a 6MPI. Secondary endpoints were CIN1+/CIN3+ associated with the same HPV type as a 6MPI; CIN1+/CIN2+/CIN3+ associated with an infection of any duration; and clearance of infection. The analyses included 4825 women with 16,785 infections (3363 women with 6902 6MPIs). Risk of developing a CIN1+/CIN2+/CIN3+ associated with same HPV type as a 6MPI varied with HPV type and was significantly higher for oncogenic versus non-oncogenic types. Hazard ratios for development of CIN2+ were 10.44 (95% CI: 6.96-15.65), 9.65 (5.97-15.60), 5.68 (3.50-9.21), 5.38 (2.87-10.06) and 3.87 (2.38-6.30) for HPV-16, HPV-33, HPV-31, HPV-45 and HPV-18, respectively. HPV-16 or HPV-33 6MPIs had ~25-fold higher risk for progression to CIN3+. Previous or concomitant HPV infection or CIN1+ associated with a different HPV type increased risk. Of the different oncogenic HPV types, HPV-16 and HPV-31 infections were least likely to clear. CONCLUSIONS: Cervical infections with oncogenic HPV types increased the risk of CIN2+ and CIN3+. Previous or concomitant infection or CIN1+ also increased the risk. HPV-16 and HPV-33 have by far the highest risk of progression to CIN3+, and HPV-16 and HPV-31 have the lowest chance of clearance.

Asunto(s)

Alphapapillomavirus , Cuello del Útero/virología , Infecciones por Papillomavirus/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/virología , Adolescente , Adulto , Cuello del Útero/metabolismo , Cuello del Útero/patología , Método Doble Ciego , Femenino , Humanos , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/patología , Factores de Riesgo , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología

RESUMEN

BACKGROUND: Public Health England has reported a decrease of up to 20.8% in new diagnoses of external genital warts (GWs) among women aged <19 years since the national vaccination program with the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine began in 2008. A post hoc analysis of the phase III PATRICIA (PApilloma TRIal against Cancer In young Adults) trial (NCT00122681) was performed to ascertain whether protection against low-risk HPV types was apparent. METHODS: Vaccine efficacy (VE) at 48 months was assessed against 6-month persistent infection (6MPI) with low-risk HPV types in the total vaccinated cohort (TVC) and in the TVC naive (for 25 HPV types tested) populations. RESULTS: In the TVC naive cohort, VE against 6MPI (95% confidence interval) was 34.5% (11.3 to 51.8) for HPV-6/11, 34.9% (9.1 to 53.7) for HPV-6, 30.3% (-45.0 to 67.5) for HPV-11, and 49.5% (21.0 to 68.3) for HPV-74. CONCLUSIONS: The HPV-16/18 AS04-adjuvanted vaccine appears to have moderate efficacy against persistent infections with a number of low-risk HPV types (HPV-6/11/74), which are responsible for the majority of external GWs, and recently, antibody and cell-mediated immune response to HPV-6/11 have been observed. These findings may help to explain the decrease in external GW diagnoses seen in England.

Asunto(s)

Adyuvantes Inmunológicos/administración & dosificación , Hidróxido de Aluminio/administración & dosificación , Condiloma Acuminado/prevención & control , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 18/inmunología , Lípido A/análogos & derivados , Vacunación , Ensayos Clínicos Fase III como Asunto , Condiloma Acuminado/epidemiología , Condiloma Acuminado/inmunología , Método Doble Ciego , Femenino , Papillomavirus Humano 6/inmunología , Humanos , Incidencia , Hallazgos Incidentales , Lípido A/administración & dosificación , Estudios Multicéntricos como Asunto , Vacunas contra Papillomavirus , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento

RESUMEN

PURPOSE: This study proposes to assess MBL serum concentrations in HPV positive women that developed high risk preinvasive lesions, CIN III. MATERIALS AND METHODS: A total of 90 consecutive women (mean age 32.2 years, range 18-45 years) with CIN III lesions confirmed by cone biopsy were enrolled as cases at the gynecology cancer department of the Erasto Gaertner Hospital, a center of reference for cancer treatment in Southern Brazil. All the patients were HPV positive. In addition, 81 healthy women, voluntary blood donors, were enrolled as healthy control subjects (mean age 33.3 years, range 14-71 years) with no evidence of HPV infection, tested by hybrid capture, or CIN lesions, from the same geographic area. RESULTS: The median concentration of MBL in the cases was 912 ng/ml (IQR: 100-5820 ng/ml) and in the controls was 1207.3 ng/ml (IQR 100-4320.6 ng/ml). No statistically significant difference was observed between cases and controls. CONCLUSION: This study reports data on MBL serum concentrations in HPV infected women for the first time. The analysis of our findings did not show a statistically significant difference between MBL serum concentrations in HPV women that developed CIN III lesions and healthy controls.

Asunto(s)

Lectina de Unión a Manosa/sangre , Papillomaviridae , Infecciones por Papillomavirus/sangre , Displasia del Cuello del Útero/sangre , Neoplasias del Cuello Uterino/sangre , Adolescente , Adulto , Anciano , Biopsia , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/complicaciones , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/complicaciones , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virología

RESUMEN

BACKGROUND: The causal association between persistent human papillomavirus (HPV) infection and cervical cancer has been established, but the mechanisms that favor HPV persistence in cervical cells are still unknown. The diminished capability of the immune system to control and resolve HPV infection is one of several hypotheses. The tolerogenic protein HLA-G has shown aberrant expression in a variety of cancers, which has been suggested as a mechanism for tumor escape from immunosurveillance. In the present study we evaluate the role of epigenetic modification (promoter de-methylation) of the HLA-G gene on susceptibility to HPV infection and development of high-grade cervical lesions. METHODS: A case-control study was carried out in Curitiba, Brazil, between February and June 2010. A total of 789 women aged 15-47 years were recruited: 510 controls with normal cervical cytology, and 279 cases with histologically confirmed cervical intraepithelial neoplasia grade 2 (CIN2, N = 150) or grade 3 (CIN3, N = 129). All women were administered a questionnaire by interview, which collected information on demographic and lifestyle factors, and a cervical sample was collected. HPV DNA detection was performed by GP5+/GP6+ primer-mediated PCR. HPV-positive samples were genotyped by multiplex PCR. A pilot analysis of HLA-G promoter methylation was carried out in a subset of the study population (96 cases and 76 controls) by pyrosequencing. HLA-G methylation and HPV infection status of cases and controls were compared, and confounding factors were computed by t Student and non-parametric Wilcoxon tests. Comparison of HLA-G methylation between cases and controls was assessed by the Bonferroni correction. The association of HLA-G methylation with CIN2/3 was evaluated by logistic regression. RESULTS: HPV prevalence was 19.6% in controls and 94.3% in CIN2/3 cases. HPV16, 31, 33, 35 and 18 were the most prevalent types. Methylation analysis of seven CpGs in the HLA-G promoter did not reveal any spontaneous de-methylation events in CIN2/3 cases (mean proportion of methylation: 75.8%) with respect to controls (mean 73.7%; odds ratio 1.01, 95% confidence interval 0.96, 1.07). CONCLUSIONS: This study did not support the hypothesis that spontaneous de-methylation events in the HLA-G promoter play a primary role in promoting escape from immunosurveillance in the development of precancerous cervical lesions.

Asunto(s)

Antígenos HLA-G/genética , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/genética , Displasia del Cuello del Útero/genética , Neoplasias del Cuello Uterino/genética , Adolescente , Adulto , Brasil , Estudios de Casos y Controles , Metilación de ADN , ADN Viral/análisis , Femenino , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Papillomaviridae/genética , Proyectos Piloto , Prevalencia , Regiones Promotoras Genéticas/genética , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/virología

RESUMEN

OBJECTIVE: We evaluated baseline data from the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681) on the association between behavioral risk factors and HPV infection and cervical abnormalities. METHODS: Women completed behavioral questionnaires at baseline. Prevalence of HPV infection and cervical abnormalities (detected by cytological or histological procedures) and association with behavioral risk factors were analyzed by univariate and stepwise multivariable logistic regressions. RESULTS: 16782 women completed questionnaires. Among 16748 women with data for HPV infection, 4059 (24.2%) were infected with any HPV type. Among 16757 women with data for cytological abnormalities, 1626 (9.7%) had a cytological abnormality, of whom 1170 (72.0%) were infected with at least one oncogenic HPV type including HPV-16 (22.7%) and HPV-18 (9.3%). Multivariable analysis (adjusted for age and region, N=14404) showed a significant association between infection with any HPV type and not living with a partner, smoking, age <15 years at first sexual intercourse, higher number of sexual partners during the past 12 months, longer duration of hormonal contraception and history of sexually transmitted infection (STI). For cervical abnormalities, only history of STI (excluding Chlamydia trachomatis) remained significant in the multivariable analysis after adjusting for HPV infection. CONCLUSIONS: Women reporting 3+ sexual partners in the past 12 months had the highest risk of HPV infection at baseline. HPV infection was the main risk factor for cervical abnormalities, and history of STIs excluding Chlamydia trachomatis increased risk to a lesser extent. Although behavioral factors can influence risk, all sexually active women are susceptible to HPV infection.

Asunto(s)

Cuello del Útero/patología , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/etiología , Enfermedades del Cuello del Útero/epidemiología , Enfermedades del Cuello del Útero/etiología , Neoplasias del Cuello Uterino/prevención & control , Adolescente , Adulto , Cuello del Útero/virología , Femenino , Humanos , Modelos Logísticos , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/virología , Vacunas contra Papillomavirus , Prevalencia , Factores de Riesgo , Enfermedades del Cuello del Útero/prevención & control , Enfermedades del Cuello del Útero/virología , Vacunación , Adulto Joven

RESUMEN

Prophylactic human papillomavirus (HPV) vaccines are now available and vaccination programs are being widely implemented, targeting adolescent girls prior to sexual debut. Since the risk of HPV exposure persists throughout a woman's sexual life, the duration of protection provided by vaccination is critical to the overall vaccine effectiveness. We report the long-term efficacy and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine (Cervarix (®) ) up to 8.4 y after the first vaccine dose.   In an initial placebo-controlled study performed in US, Canada and Brazil, women aged 15-25 y with normal cervical cytology, HPV-16/18 seronegative by ELISA, DNA-negative for 14 oncogenic HPV types by PCR, received either the HPV-16/18 vaccine or placebo (n = 1,113). Subjects were followed up to 6.4 y after the first dose (n = 776). We report an additional 2-y follow-up for women enrolled from the Brazilian centers from the initial study (n = 436). During the current follow-up study (HPV-023, NCT00518336), no new infection or lesions associated with HPV-16/18 occurred in the vaccine group. Vaccine efficacy over the entire follow-up (up to 8.4 y) was 95.1% (84.6, 99.0) for incident infection, 100% (79.8, 100) for 6-mo persistent infection, 100% (56.1, 100) for 12-mo persistent infection and 100% (< 0, 100) for CIN2+ associated with HPV-16/18. All women in the vaccine group remained seropositive to both HPV-16/18, with antibody titers for total and neutralizing antibodies remaining several-folds above natural infection levels. The safety profile was clinically acceptable for both vaccine and control groups. This is, to date, the longest follow-up study for a licensed cervical cancer vaccine.

Asunto(s)

Anticuerpos Antivirales/sangre , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Vacunas contra Papillomavirus/inmunología , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Adolescente , Adulto , Brasil , Canadá , Femenino , Estudios de Seguimiento , Humanos , Placebos/administración & dosificación , Embarazo , Factores de Tiempo , Estados Unidos , Adulto Joven

RESUMEN

BACKGROUND: Cervical intraepithelial neoplasia grade 2 or greater (CIN2+) is the surrogate endpoint used in licensure trials of human papillomavirus (HPV) vaccines. Vaccine efficacy against CIN3+, the immediate precursor to invasive cervical cancer, is more difficult to measure because of its lower incidence, but provides the most stringent evidence of potential cancer prevention. We report vaccine efficacy against CIN3+ and adenocarcinoma in situ (AIS) in the end-of-study analysis of PATRICIA (PApilloma TRIal against Cancer In young Adults). METHODS: Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA, irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to receive an HPV-16/18 AS04-adjuvanted vaccine or a control hepatitis A vaccine via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The patients and study investigators were masked to allocated vaccine. The primary endpoint of PATRICIA has been reported previously. In the present end-of-study analysis, we focus on CIN3+ and AIS in the populations of most clinical interest, the total vaccinated cohort (TVC) and the TVC-naive. The TVC comprised all women who received at least one vaccine dose, approximating catch-up populations and including sexually active women (vaccine n=9319; control=9325). The TVC-naive comprised women with no evidence of oncogenic HPV infection at baseline, approximating early adolescent HPV exposure (vaccine n=5824; control=5820). This study is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Vaccine efficacy against CIN3+ associated with HPV-16/18 was 100% (95% CI 85·5-100) in the TVC-naive and 45·7% (22·9-62·2) in the TVC. Vaccine efficacy against all CIN3+ (irrespective of HPV type in the lesion and including lesions with no HPV DNA detected) was 93·2% (78·9-98·7) in the TVC-naive and 45·6% (28·8-58·7) in the TVC. In the TVC-naive, vaccine efficacy against all CIN3+ was higher than 90% in all age groups. In the TVC, vaccine efficacy against all CIN3+ and CIN3+ associated with HPV-16/18 was highest in the 15-17 year age group and progressively decreased in the 18-20 year and 21-25 year age groups. Vaccine efficacy against all AIS was 100% (31·0-100) and 76·9% (16·0-95·8) in the TVC-naive and TVC, respectively. Serious adverse events occurred in 835 (9·0%) and 829 (8·9%) women in the vaccine and control groups, respectively; only ten events (0·1%) and five events (0·1%), respectively, were considered to be related to vaccination. INTERPRETATION: PATRICIA end-of-study results show excellent vaccine efficacy against CIN3+ and AIS irrespective of HPV DNA in the lesion. Population-based vaccination that incorporates the HPV-16/18 vaccine and high coverage of early adolescents might have the potential to substantially reduce the incidence of cervical cancer. FUNDING: GlaxoSmithKline Biologicals.

Asunto(s)

Adenocarcinoma/prevención & control , Adyuvantes Inmunológicos/administración & dosificación , Hidróxido de Aluminio/administración & dosificación , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 18/inmunología , Lípido A/análogos & derivados , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Displasia del Cuello del Útero/prevención & control , Neoplasias del Cuello Uterino/prevención & control , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Adenocarcinoma/virología , Adolescente , Adulto , Factores de Edad , Asia , Australia , ADN Viral/análisis , Método Doble Ciego , Europa (Continente) , Femenino , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Lípido A/administración & dosificación , Clasificación del Tumor , América del Norte , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/virología , América del Sur , Factores de Tiempo , Resultado del Tratamiento , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Adulto Joven , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/virología

RESUMEN

Group B streptococcal (GBS) capsular polysaccharide (CPS)-based conjugate vaccine, which includes types Ia, Ib, II, III, and V, could potentially prevent neonatal, pediatric, adult, and pregnancy-associated diseases. However, since GBS CPS types included in that vaccine are prevalent serotypes found in North America and Europe, it may not provide the necessary protection for individuals in countries in which other capsular types have been found.

Asunto(s)

Polisacáridos Bacterianos/inmunología , Infecciones Estreptocócicas/prevención & control , Vacunas Estreptocócicas/inmunología , Streptococcus agalactiae/clasificación , Femenino , Humanos , Inmunización , Embarazo , Prevalencia , Serotipificación , Infecciones Estreptocócicas/epidemiología , Vacunas Estreptocócicas/administración & dosificación , Streptococcus agalactiae/inmunología , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/inmunología