Five human papillomaviruses (HPV), HPV types 6, 11, 16, 18 and 31, infect the genital tract. Examination of genital tract tumors for vital DNA sequences has shown that HPV-6 and HPV-11 are recovered most often from benign lesions and HPV-16 and HPV-18 most often from premalignant and malignant tissues. The proposed investigation will compare, prospectively, the risks of genital tract infection with different HPV genotypes. One population will consist of 400 newly diagnosed, consecutive patients attending The Johns Hopkins Hospital Colposcopy Clinics. They will be monitored virologically for 3-5 years. The infecting viral genotype will be identified by Southern transfer hybridization of DNA extracted from cervical scrapings. The identity of the genotype will not be known to the clinicians. The patients will receive regular treatment on the basis of colposcopic, cytologic and histologic follow-up according to The Johns Hopkins protocol. Correlation of virologic and clinical data will be made to describe the spectrum of pathologic abnormalities and the outcome of infection (return to normal cytology, persistent abnormal cytology, need for conization, etc.), associated with each genotype. Sera will be collected from patients for future immunological studies of antibody response to documented infections. Additionally, advantage will be taken of the recently developed in situ hybridization test to identify HPV genotypes in paraffin sections of cervical biopsies of about 2,000 participants in previous prospective studies of cervical abnormalities in Chile and New Zealand. These patients have been monitored carefully for 5-30 years and the outcome of disease is already known for many of them. Disease progression, including invasive cancer, has been seen in a number of these participants, in both studies. Identification of infecting HPV genotypes in the first biopsies of all study participants, and the correlation of virologic data with the already collected clinical and pathologic information, will reveal the spectrum of disease associated with each genotype and allow a comparison of the genotypes with respect to the risk of disease progression. The etiologic association of specific genotypes to cervical cancer will be strengthened if similar trends are seen in each of three geographic locations. The study will aid in evaluating the etiologic role of specific HPVs in cervical cancer and may help in the development of strategies for treatment and prevention.
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