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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.