RESUMO
BACKGROUND AND OBJECTIVES: Strong epidemiologic evidence indicates that human papillomavirus (HPV) is the main etiologic factor of cervical cancer. A few cohort studies suggest that most HPV infections are transient in young women and that persistent HPV infections are more common in older women. Little is known about the determinants of persistent HPV infections. The present study was aimed at increasing our knowledge about these determinants. GOALS: To identify risk factors for genital HPV DNA detection among cytologically normal middle-aged women. STUDY DESIGN: Eight hundred ten women who participated as control subjects in three case-control studies on cervical cancer in Spain, Colombia, and Brazil were included in this study. After an interview, women underwent a gynecologic examination with collection of exfoliated cells for a Papanicolaou smear and HPV DNA detection. Human papilloma virus DNA was detected by polymerase chain reaction (PCR)-based hybridization techniques. RESULTS: The HPV positivity rate was 10.5% in the whole population, but was higher in the areas with high incidence of cervical cancer (17% in Brazil and 13% in Colombia) than in Spain (4.9%), which is a low-risk area for cervical cancer. Age was related to the prevalence of HPV DNA in Brazil, but not in Spain and Colombia. In univariate analyses in all three countries, the prevalence of HPV DNA was positively associated with the number of lifetime sexual partners and inversely associated with the levels of family income and with age at first sexual intercourse. There was four times increase in the odds ratio (OR) of HPV infection in women who had six or more lifetime sexual partners compared with those with one or less. The use of any kind of contraceptive tended to decrease the OR for HPV detection. Their ORs ranged from 0.44 (barrier methods) to 0.48 (oral contraceptives). In Spain and Colombia, antibodies against Chlamydia trachomatis were positively associated with the prevalence of HPV DNA. In a final multivariate model, the positive associations with lifetime number of sexual partners, socioeconomic status, and C. trachomatis persisted. CONCLUSIONS: These results support the sexual transmission of HPV and suggest that socioeconomic status and antibodies to C. trachomatis are independent predictors of HPV detection in middle-aged cytologically normal women.
Assuntos
Papillomaviridae , Infecções por Papillomavirus/epidemiologia , Infecções Tumorais por Vírus/epidemiologia , Adulto , Fatores Etários , Brasil/epidemiologia , Infecções por Chlamydia/complicações , Chlamydia trachomatis , Colômbia/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Reação em Cadeia da Polimerase , Prevalência , História Reprodutiva , Fatores de Risco , Estudos Soroepidemiológicos , Comportamento Sexual , Fatores Socioeconômicos , Espanha/epidemiologiaRESUMO
Data from four case-control studies on invasive cervical cancer and on cervical intraepithelial neoplasia grade III (CIN III) that were concurrently conducted in Spain and Colombia were used to look for factors that might favor the progression from CIN III to the invasive stage. These studies were compared in two ways; a case-case comparison and an estimation of the ratio of odds ratios with the use of of special logistic regression model that took into account the different design of each study and possible confounding factors. Variables studied were human papillomavirus status, viral load, viral types, sexual behavior, sexually transmitted diseases, reproductive patterns, oral contraceptives, and smoking. Both CIN III and invasive cervical cancer have a very similar profile of risk factors and none of them was different in a consistent way to suggest a role in the progression from CIN III to invasive cervical cancer. Some methodological problems such as cohort-specific differences and some selection biases could be adjusted for with a careful statistical analysis. Other problems derived from the cross-sectional nature of the design are unavoidable and should be considered in the interpretation of the results.
Assuntos
Transformação Celular Neoplásica/patologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Estudos de Casos e Controles , Colômbia/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Paridade , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Comportamento Sexual , Infecções Sexualmente Transmissíveis/complicações , Fatores Socioeconômicos , Espanha/epidemiologia , Neoplasias do Colo do Útero/etiologiaRESUMO
Two case-control studies, including 449 histologically confirmed cases of cervical intra-epithelial neoplasia (CIN) III and 425 controls, and 2 studies on invasive cervical cancer, involving 316 histologically confirmed cases and 330 population controls, were conducted in Colombia and Spain to assess the role of herpes simplex virus type 2 (HSV-2) in cervical neoplasia. Antibodies to this virus were also measured in the sera of 931 husbands of cases and controls. A serological assay using type-specific antigens, glycoprotein C for type I (gC-I) and glycoprotein G for type 2 (gG-2) was employed. Immunoglobulin-G (IgG) sub-classes, IgG1 and IgG3, were measured in women positive for HSV-2 antibodies. No increase in risk of CIN III or invasive cancer was found in women whose sera or whose husbands' sera were positive to HSV-2. However, compared with women negative to HSV-2, the risk of CIN III progressively increased with increasing levels of IgG1. The trend was statistically significant in Colombia. There was also a statistically significant increasing trend in risk of invasive cancer with levels of IgG1 in Spain. The levels of IgG3 and its ratio to IgG1, which may indicate recurrent infections, were not associated with the risk of either type of cancer. When the association with IgG1 was analyzed by human papillomavirus (HPV) DNA status, as determined by polymerase chain reaction, the trend was clearer in women whose HPV status was not determined or in those with negative HPV DNA. These results suggest that the role of HSV-2 is merely marginal and do not support the hypothesis that recurrent HSV-2 infections are of importance for cervical neoplasia.
Assuntos
Herpesvirus Humano 2/patogenicidade , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Fatores Etários , Anticorpos Antivirais/sangue , Estudos de Casos e Controles , Sondas de DNA de HPV , Feminino , Herpes Genital/complicações , Herpesvirus Humano 2/imunologia , Humanos , Imunoglobulina G/sangue , Modelos Logísticos , Masculino , Razão de Chances , Paridade , Recidiva , Fatores de Risco , Neoplasias do Colo do Útero/imunologia , Displasia do Colo do Útero/imunologiaRESUMO
Case-control studies of cervical intra-epithelial neoplasia grade III (CIN III) and of invasive cervical cancer were carried out in Spain and Colombia to assess the relationship between cervical cancer and 6 common sexually transmitted agents (STAs). The CIN-III studies included 525 cases and 512 controls matched for age and for the place of recruitment; the invasive-cancer studies included 373 histologically confirmed cases of squamous-cell carcinoma and 387 age-stratified controls selected randomly from the populations that generated the cases. Antibodies to Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, herpes simplex virus type II (HSV-2) and cytomegalovirus (CMV) were tested in 88% of the women. Cervical scrapes were examined for HPV DNA in 63% of the women using a polymerase-chain-reaction assay (PCR). Among controls, the highest antibody prevalence was to CMV (96.5%), followed by HSV-2 (31.4%) and C. trachomatis (23.3%). For all STAs, the sero-prevalence was markedly higher in Colombia than in Spain both for cases and for controls. After adjustment for the presence of HPV DNA, C. trachomatis was the only STA associated with CIN III in both countries; Spain and Colombia. In both countries, the risk of CIN III increased with increasing of C. trachomatis antibody titers. Among Spanish women, an increase in risk of invasive carcinoma was found for those with antibodies to N. gonorrhoeae; those with antibodies to HSV-2 and those with antibodies to C. trachomatis. These associations were present only in HPV-DNA-negative women. Among HPV-DNA-positive women, none of the STAs considered were associated with cervical neoplasia. Our findings could be interpreted as indicating that past infections with HSV-2, N. gonorrhoeae and C. trachomatis are surrogate markers of HPV, but because HPV DNA may have escaped detection, we cannot exclude that these STAs are also of separate etiological significance.
Assuntos
Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis , Gonorreia/epidemiologia , Comportamento Sexual , Infecções Sexualmente Transmissíveis/epidemiologia , Sífilis/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Estudos de Casos e Controles , Infecções por Chlamydia/complicações , Infecções por Chlamydia/diagnóstico , Colômbia/epidemiologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Feminino , Gonorreia/complicações , Gonorreia/diagnóstico , Herpes Simples/complicações , Herpes Simples/diagnóstico , Herpes Simples/epidemiologia , Humanos , Invasividade Neoplásica , Reação em Cadeia da Polimerase , Prevalência , Trabalho Sexual , Infecções Sexualmente Transmissíveis/complicações , Infecções Sexualmente Transmissíveis/diagnóstico , Espanha/epidemiologia , Sífilis/complicações , Sífilis/diagnóstico , Neoplasias do Colo do Útero/complicaçõesRESUMO
The objectives of this study were to confirm the hypothesis that invasive carcinoma of the uterine cervix and the precursors of that condition are most often caused by human papilloma virus (HPV) infections, and to determine whether or not other risk factors are involved in the neoplastic process. For this purpose, four concurrent case-control studies were carried out. Two included cases of invasive cervical cancer and population-based controls. The other two included cases of in situ carcinoma and controls. Research was carried out in nine provinces of Spain and in Cali, Colombia. The identification of cases took place between June 1985 and June 1988. The studies included 436 incident cases of invasive carcinoma and 387 controls, selected at random from the corresponding populations, and 525 cases of in situ carcinoma and 512 controls paired by age, place of recruitment, and date that cytological specimens were taken from the women participating in cytological screening programs. Exposure to HPV was detected through hybridization tests after amplification by polymerase chain reaction (PCR) in exfoliated cervical cells from cases and controls. Exposure to HPV was the principal risk factor in the four studies. For invasive carcinoma, the relative risk and 95% confidence interval were 46.2 (18.5-115.1) in Spain and 15.6 (6.9-34.7) in Colombia. For in situ carcinoma, the figures were 56.9 (24.8-130.6) in Spain and 15.5 (8.2-29.4) in Colombia. This strong association was specific for types 16, 18, 31, 33, and 35 as well as still-unclassified HPV types.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções Tumorais por Vírus/complicações , Neoplasias do Colo do Útero/microbiologia , Carcinoma in Situ/epidemiologia , Carcinoma in Situ/microbiologia , Estudos de Casos e Controles , Colômbia , Feminino , Humanos , Invasividade Neoplásica , Fatores de Risco , Espanha , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologiaRESUMO
A case-control study of 525 cases of cervical intraepithelial neoplasia grade III (CIN III) and 512 controls was conducted in Spain and Colombia between 1985 and 1988 to assess the role of human papillomavirus (HPV) in the etiology of CIN III. HPV DNA in cytological scrapes from the cervix was assessed by Virapap and by polymerase chain reaction (PCR) based on the L1 consensus primers. A subsample of 268 specimens was also tested for HPV DNA using Southern hybridization. In Spain, the PCR-based prevalences of HPV DNA were 70.7% among cases and 4.7% among controls. Odds ratio (OR) and 95% confidence interval (numbers in parentheses) for HPV DNA were 56.9 (24.8-130.6). In Columbia HPV DNA was detected by PCR in 63.2% of the cases and in 10.5% of the controls. The OR was 15.5 (8.2-29.4). The estimated fractions of CIN III attributable to HPV were 72.4% in Spain and 60.3% in Colombia. HPV 16 was the predominant viral type and showed the strongest association with CIN III; in Spain the OR was 295.5 (44.8-1946.4) and in Colombia the OR was 27.1 (10.6-69.5). HPV DNA of unknown type was frequent in HPV-positive cases (18.3% in Spain and 38.0% in Colombia) and controls (66.7% in Spain and 47.4% in Colombia). The comparison of results from Virapap and PCR indicated that PCR is the method of choice for epidemiological studies. These data strongly support the hypothesis of the viral origin of CIN III, the common etiology of CIN III and invasive cervical cancer, and the causal nature of the association between HPV and CIN III.
Assuntos
Carcinoma in Situ/epidemiologia , Carcinoma in Situ/microbiologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções Tumorais por Vírus/epidemiologia , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/microbiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/microbiologia , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Colômbia/epidemiologia , Fatores de Confusão Epidemiológicos , DNA Viral/análise , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Hibridização de Ácido Nucleico , Papillomaviridae/classificação , Papillomaviridae/genética , Reação em Cadeia da Polimerase , Prevalência , Fatores de Risco , Espanha/epidemiologiaRESUMO
Los objetivos del estudio fueron verificar la hipótesis según la cual el carcinoma invasor del cuello uterino y sus precursores son causados la mayor parte de las veces por infecciones debidas al virus del papiloma humano (VPH), y si otros factores de riesgo intervienen en el proceso neoplásico. Para ello, se realizaron cuatro estudios concurrentes de casos y controles. Dos de ellos incluyeron casos de carcinoma invasor y controles de base poblacional. Los dos restantes incluyeron casos y controles de carcinoma in situ. La investigación se realizó en nueve provincias de España y en Cali, Colombia. La identificación de casos tuvo lugar entre junio de 1985 y junio de 1988. Se incluyeron 436 casos incidentes de carcinoma invasor y 387 controles, seleccionados al azar de las poblaciones correspondientes, y 525 casos de carcinoma in situ y 512 controles apareados por edad, centro de reclutamiento y fecha de toma citológica entre mujeres participantes en programas de tamizaje citológico. La exposición al VPH se detectó mediante pruebas de hibridación tras amplificación por la reacción en cadena de la polimerasa en células cervicales exfoliadas de casos y controles. La exposición al VPH fue el factor de riesgo principal en los cuatro estudios
Assuntos
Neoplasias do Colo do Útero , Estudos de Casos e Controles , Colômbia , EspanhaRESUMO
A population-based case-control study of cervical cancer was conducted in Spain and Colombia to assess the relationship between cervical cancer and exposure to human papillomavirus (HPV), selected aspects of sexual and reproductive behaviour, use of oral contraceptives, screening practices and smoking. The study included 436 cases of histologically confirmed squamous-cell carcinoma and 387 age-stratified controls randomly selected from the general population that generated the cases. The presence of HPV DNA in cervical scrapes was assessed by PCR-based methods and was the strongest risk factor (OR = 23.8; 13.4-42.0). Risk estimates for any other factor were only slightly modified after adjusting for HPV status. Among women found positive for HPV DNA, only the use of oral contraceptives was a risk factor for cervical cancer (OR = 6.5; 1.3-31.4 for ever vs. never use). Patients with cervical cancer who were HPV DNA-negative retained most of the established epidemiological features of this disease. This suggests that some instances of HPV infection went undetected or that other sexually transmitted factor(s) contribute to the causation of cervical cancer. Early age at first intercourse (OR = 4.3; 2.1-9.0 for age < 16 vs. 24+) and early age at first birth (OR = 5.0; 1.8-14.2 for age < 16 vs. 24+) were associated with increased risk of cervical cancer; these effects were independent of one another. Low educational level was a risk factor (OR = 2.5; 1.6-3.9). Number of sexual partners was in our study a surrogate for HPV infection. Smoking and parity after age 24 were weakly and inconsistently associated with the risk of cervical cancer. Previous screening (OR = 0.7; 0.5-1.0) and ever having undergone a Caesarean section (OR = 0.4; 0.2-0.8) were protective factors.
PIP: Findings are presented from a population-based case-control study of cervical cancer conducted in Spain and Colombia to assess the relationship between cervical cancer and exposure to human papillomavirus (HPV), selected aspects of sexual and reproductive behavior, the use of oral contraceptives, screening practices, and smoking. 436 cases of histologically confirmed squamous-cell carcinoma and 387 age-stratified controls randomly selected from the general population which generated the cases participated in the study. Cases in Colombia were of mean age 46.5 years compared to 52.2 years in Spain. The presence of HPV DNA in cervical scrapes was assessed by PCR-based methods and was the most significant risk factor, with at least 70% of cervical cancer cases associated with the viral infection. Risk estimates for other factors were only slightly modified after adjusting for HPV status. Among women found positive for HPV DNA, only the use of oral contraceptives was a risk factor for cervical cancer, with patients with cervical cancer who were HPV DNA-negative retaining most of the established epidemiological features of the disease. This latter finding suggests that some cases of HPV infection were undetected or that other sexually transmitted factors contribute to the causation of cervical cancer. Early age at first intercourse and early age at first birth were independently associated with an increased risk of cervical cancer. Low educational level was a risk factor and the number of sex partners was a surrogate for HPV infection. Smoking and parity after age 24 were weakly and inconsistently associated with the risk of cervical cancer. Previous screening and ever having undergone a Caesarean section were protective factors.
Assuntos
Neoplasias do Colo do Útero/etiologia , Fatores Etários , Estudos de Casos e Controles , Colômbia , Anticoncepcionais Orais/efeitos adversos , DNA Viral/análise , Feminino , Humanos , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Paridade , Fatores de Risco , Parceiros Sexuais , Fumar , Fatores Socioeconômicos , Espanha , Infecções Tumorais por Vírus/complicaçõesRESUMO
The case of a 71-year-old patient who had respiratory disorders for more than 11 years is reported. Direct microscopy was negative in 4 sputum samples and finally, on five occasions, the culture gave rise to a strain biochemically labeled as Mycobacterium scrofulaceum. The case corresponded to a mycobacteriosis.