In 1993 the authors began an epidemiologic cohort study of the natural history of human Papillomavirus (HPV) infection and cervical neoplasia in a population of low income women in Sao Paulo, Brazil, one of the highest risk areas worldwide for cervical cancer. This study was designed to answer questions that have not yet been addressed in epidemiologic investigations of this neoplastic disease. Although few would dispute that HPV infection is an important cause of cervical cancer, most of the epidemiologic data have come from retrospective studies, which do not provide information on the dynamics of cervical HPV infection in the same individual. The Brazilian cohort study is testing the hypothesis that persistent infections with oncogenic HPV types are more likely to be the true precursor events leading to cervical carcinogenesis. Persistence of infections is being documented on the basis of molecular variants of HPV, which provides a much finer level of detail than simple HPV typing and may unveil in addition to persistence per se other prognostic markers of progression across the spectrum of cervical lesions. The study will accrue 2000 female subjects through February 1996. Subjects are being followed up over a 5 year period in scheduled returns every 4 months, in the first year, and once yearly thereafter, for a total of 8 visits as follows: initial, 4, 8, 12, 24, 36, 48, and 60 months. In each of these visits, subjects are submitted to a questionnaire-based interview, have a cervical specimen taken for Pap cytology and HPV testing, and a blood sample drawn for serologic testing for HPV antibodies. A cervicography is performed once in the first year and at 24 and 48 months. Considering the public health and economic importance of cervical cancer screening and given the current impetus within the federal government to examine the utility of HPV testing in augmenting existing screening programs, the investigators argue that there is a clear need for long-ranging multidisciplinary studies of the natural history of this malignant disease. In brief, this ongoing investigation will further understanding of the etiopathogenesis of cervical neoplasia by tackling the following specific objectives: (1) to study the prevalence and incidence of transient and persistent cervical HPV infection in asymptomatic women; (2) to verify the hypothesis that persistent HPV infection increases risk of low grade and high grade cervical lesions; (3) to search for epidemiologic determinants of persistent cervical HPV infection; (4) to search for specific molecular variants of oncogenic types of HPV that may be associated with an increased risk of cervical neoplasia; (5) to verify the hypothesis that measures of viral burden in the cervix may be correlated with persistent infections and with low and high grade lesions; and (6) to study the humoral immune response to capsid antigens of HPV as a possible marker of persistence of cervical HPV infection and of likelihood of progression in lesion severity.
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