RESUMO
Increased understanding of human papillomavirus (HPV) infection as the central cause of cervical cancer has permitted the development of improved screening techniques. To evaluate their usefulness, we evaluated the performance of multiple screening methods concurrently in a large population-based cohort of >8500 nonvirginal women without hysterectomies, whom we followed prospectively in a high-risk region of Latin America. Using Youden's index as a measure of the trade-off between sensitivity and specificity, we estimated the performances of a visual screening method (cervicography), conventional cytology, liquid-based cytology (ThinPrep), and DNA testing for 13 oncogenic HPV types. The reference standard of disease was neoplasia > or = cervical intraepithelial neoplasia grade 3 (CIN 3), defined as histologically confirmed CIN 3 detected within 2 years of enrollment (n=90) or invasive cancer detected within 7 years (n=20). We analyzed each technique alone and in paired combinations (n=112 possible strategies), and evaluated the significance of differences between strategies using a paired Z test that equally weighted sensitivity and specificity. As a single test, either liquid-based cytology or HPV DNA testing was significantly more accurate than conventional cytology or cervicography. Paired tests incorporating either liquid-based cytology or HPV DNA testing were not substantially more accurate than either of those two test strategies alone. However, a possibly useful synergy was observed between the conventional smear and cervicography. Consideration of age or behavioral risk profiles did not alter any of these conclusions. Overall, we conclude that highly accurate screening for cervical cancer and CIN 3 is now technically feasible. The remaining vital issue is to extend improved cervical cancer prevention programs to resource-poor regions.
Assuntos
Programas de Rastreamento/métodos , Papillomaviridae , Infecções Tumorais por Vírus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Idoso , Estudos de Coortes , Costa Rica , DNA Viral/análise , Feminino , Humanos , Programas de Rastreamento/economia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade , Infecções Tumorais por Vírus/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/epidemiologiaRESUMO
To comprehensively explore the relationship between human leukocyte antigen (HLA) class I alleles and cervical neoplasia, a subset of participants from 3 large US and Costa Rican cervix studies were typed for HLA class I alleles. Study subjects were women with cervical cancer or high-grade squamous epithelial lesions (HSILs; n=365) or low-grade squamous epithelial lesions (LSILs; n=275) or who were cytologically normal (control subjects; n=681). Allele-disease associations were assessed by logistic regression analysis. Consistent associations across all studies were observed for HLA-CW*0202 with a combined odds ratio of 0.53 (95% confidence interval [CI], 0.29-0.89) for cancer or HSILs and 0.58 (95% CI, 0.37-1.04) for LSILs, compared with control subjects and adjusted for study. This finding supports the hypothesis that a single allele may be sufficient to confer protection against cervical neoplasia. Given the relationship between HLA-C and its receptors on natural killer (NK) cells, a role is proposed for NK function in human papillomavirus infection and cervical neoplasia.
Assuntos
Alelos , Carcinoma de Células Escamosas/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Neoplasias do Colo do Útero/imunologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/virologia , Estudos de Coortes , Costa Rica , DNA Viral/química , DNA Viral/genética , Feminino , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Modelos Logísticos , Oregon , Papillomaviridae/genética , Papillomaviridae/imunologia , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/imunologia , Reação em Cadeia da Polimerase , Infecções Tumorais por Vírus/genética , Infecções Tumorais por Vírus/imunologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologiaAssuntos
Genes MHC Classe I/genética , Predisposição Genética para Doença , Infecções por Papillomavirus/complicações , Infecções Tumorais por Vírus/complicações , Neoplasias do Colo do Útero/genética , Adulto , Estudos de Coortes , Costa Rica/epidemiologia , DNA Viral/análise , Feminino , Humanos , Perda de Heterozigosidade , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/prevenção & controle , Reação em Cadeia da Polimerase , Fatores de Risco , Infecções Tumorais por Vírus/prevenção & controle , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/prevenção & controleRESUMO
En el presente trabajo se describe la fase de reclutamiento de un estudio poblacional sobre la historia natural de las neoplasias de cuello uterino en Guanacaste, provincia rural costarricense donde las tasas de cáncer cervicouterino invasor son invariablemente altas. Las metas principales del estudio son investigar el papel que desempeñan la infección por el virus del papiloma humano (VPH) y sus cofactores en la etiología de las neoplasias cervicouterinas de alto grado, y evaluar las nuevas tecnologías empleadas en el tamizaje del cáncer cervical. Para empezar se seleccionó una muestra aleatoria de segmentos censuales y, con la ayuda de trabajadores de acción comunitaria del Ministerio de Salud de Costa Rica, se hizo un recuento de todas las habitantes de 18 años de edad o mayores. De las 10 738 mujeres que cumplían con los requisitos para participar, 10 049 (93,6%) fueron entrevistadas después de haber dado su consentimiento informado por escrito. Después de la entrevista sobre los factores de riesgo del cáncer cervicouterino, se hizo un examen pélvico a las mujeres que dijeron haber tenido actividad sexual. El examen pélvico incluyó la determinación del pH vaginal y la obtención de células para análisis citológico mediante tres técnicas distintas. También se obtuvieron células cervicales para determinar la presencia y cantidad de ADN de 16 tipos de VPH diferentes y se tomaron dos fotografías del cérvix que fueron interpretadas en un local distinto por un experto en colposcopia. Por último, se sacaron muestras de sangre para hacer ensayos inmunológicos y determinaciones de micronutrientes. Las mujeres con un diagnóstico citológico anormal o un cervigrama positivo, más una muestra del grupo en general, fueron remitidas para hacerles colposcopia y se tomaron biopsias cuando se observaron lesiones. El tamizaje con fines de reclutamiento servirá de base para un estudio de prevalencia de casos y controles, y las integrantes de la cohorte sin enfermedad avanzada tendrán un seguimiento activo a intervalos mínimos de un año, con el propósito de estudiar la historia natural de la infección por VPH y los orígenes de las lesiones escamosas intraepiteliales de alto grado. Se describe en detalle la operación de campo y se hace especial alusión a la realización de estudios de este tipo en países en desarrollo. También se presentan datos descriptivos sobre la prevalencia de la enfermedad y la exposición a diversos factores de riesgo
This paper reports on the enrollment phase of a population-based natural history study of cervical neoplasia in Guanacaste, a rural province of Costa Rica with consistently high rates of invasive cervical cancer. The main goals of the study are to investigate the role of human papillomavirus (HPV) infection and its co-factors in the etiology of high-grade cervical neoplasia, and to evaluate new cervical cancer screening technologies. To begin, a random sample of censal segments was selected and enumeration of all resident women 18 years of age and over was conducted with the aid of outreach workers of the Costa Rican Ministry of Health. Of the 10 738 women who were eligible to participate, 10 049 (93.6%) were interviewed after giving written informed consent. After the interview on cervical cancer risk factors was administered, a pelvic examination was performed on those women who reported previous sexual activity. The pelvic examination included a vaginal pH determination and collection of cervical cells for cytologic diagnosis using three different techniques. Additional cervical cells were collected for determination of the presence and amount of DNA from 16 different types of HPV, and two photographic images of the cervix were taken and interpreted offsite by an expert colposcopist. Finally, blood samples were collected for immunologic and micronutrient assays. Women with any abnormal cytologic diagnosis or a positive Cervigram, as well as a sample of the whole group, were referred for colposcopy, and biopsies were taken when lesions were observed. The enrollment screening will serve as the basis for a prevalent case-control study, and the members of the cohort free from serious disease will be followed actively, at intervals of no more than a year, to study the natural history of HPV infection and the origins of high-grade squamous intraepithelial lesions (HSIL). Details of the field operation are outlined, with particular reference to the realization of this kind of study in developing countries. Descriptive data on the prevalence of disease and exposure to various risk factors are also presented.