THE PRESENCE OF PERSISTENT HIGH-RISK HPV GENOTYPES IN DYSPLASTIC CERVICAL LESIONS IS ASSOCIATED WITH PROGRESSIVE DISEASE - NATURAL-HISTORY UP TO 36 MONTHS

To evaluate the clinical significance of HPV genotyping for the predic tion of progressive cervical intraepithelial neoplasia (CIN) in women with cytomorphologically abnormal smears, a prospective, blind, non-in tervention study was performed. A total of 342 patients screened with cytomorphologically abnormal cervical smears were monitored every 3-4 months by cervical cytology, colposcopy and HPV testing using PCR. Wom en with progressive CIN disease were defined as patients developing le sions with a colposcopic impression of CIN III over more than 2 quadra nts or resulting in a cytological smear equivalent to Pap 5. These pat ients were subsequently treated according to standard procedures. If a ny doubt arose about the true status of the patients (n = 75) these pa tients were censored and biopsied. The mean follow-up time was 16.5 mo nths (range 3-36 months). Nineteen women showed progressive CIN diseas e and all appeared to be continuously HPV-positive from the start of t he study. At biopsy, all these patients were histologically classified as CIN III. Seventeen of these women were positive for high-risk HPV types. Two cases were classified as still unidentified HPV. No progres sion was seen in the absence of HPV DNA or in the presence of low-risk HPV types. In life-table analysis the cumulative rate of progressive, histologically verified CIN disease was 17% after 36 months. Further analyses showed that other risk factors such as age, sexarche, number of sexual partners or smoking hardly influenced the effect of HPV on p rogression. The results show that the continuous presence of high-risk HPV types in women with cytomorphologically abnormal smears is a stro ng marker for progressive CIN disease. (C) 1995 Wiley-Liss, Inc.