It is the objective of the proposed investigation to determine the causal role of HPV types 16 and 18, as well as other relevant types in the etiology of human cervical cancer either alone or in combination with other known or suspected risk factors. Some 10,600 women aged 20-29 years will be selected at random among residents of these age groups in the municipality of Copenhagen, Denmark. They will be invited personally to participate in the study comprising the collection of information on potential risk factors by questionnaire, and an initial gynecological screening. Cells will be collected from the portio and endocervical canal, a cervical-vaginal smear will be taken, and 10 ml of blood will be drawn. Cervical epithelial cells will be stored as well as serum at - 80 degrees C. All cervical smears will be subjected immediately to diagnosis of cervical neoplasia. The women enrolled in the study will be followed up by computerized record linkage with the Danish Central Population Register, the National Death Register, the National Danish Cancer Register, and the pathology registers. By this procedure cases of cervical neoplasia as well as women with persisting normal smears will be identified; women will be invited for a rescreen, including the collection of cervical epithelial cells for HPV hybridization three years after the initial screening. During a three year follow-up period an estimated 101 cases of severe dysplasia and carcinoma in situ will develop among women with a normal smear at the initial screening period. Five controls with a normal smear will be individually matched to these cases. For cases and controls, typespecific diagnostics of HPV in the initial scrape will be performed by Vira-Pap and Vira-Type; and possibly using PCR-technique. HSV-II antibodies in the sera will be diagnosed by ELISA-technique. Analysis will be performed as a matched case-control nested within the cohort.
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