A PROSPECTIVE-STUDY ON THE RISK OF CERVICAL INTRAEPITHELIAL NEOPLASIAAMONG HEALTHY-SUBJECTS WITH SERUM ANTIBODIES TO HPV COMPARED WITH HPVDNA IN CERVICAL SMEARS

To estimate the risk of developing cervical intra-epithelial neoplasia (CIN) among women exposed to human papillomavirus (HPV) type 16, we p erformed a prospective study in a population-based cohort of more than 15,000 women followed for 34.9 months. Seventy-four women developed C IN during follow-up and were matched for age, time of sampling and are a of residence with 148 women who remained CIN-free during follow-up. The blood samples taken at enrollment were tested for serum antibodies to HPV types 16, 18 and 33 capsids. Cervical smears or biopsies were analyzed for the presence of HPV DNA by nested PCR using HPV general p rimers and by HPV 16- and 18-type-specific PCR. HPV serology and HPV-P CR were in good agreement, particularly when the blood sample and the Pap smear were taken less than 6 months apart. HPV DNA was found in 88 % of cases and 4% of controls, whereas HPV 16 DNA was present in 44% o f cases and in 1 of 142 controls. HPV-16-seropositive women had a 3-fo ld increased risk of developing CIN. The risk was highest among women younger than 35 years of age, of whom an estimated 3.4% of HPV-16-sero positive and 0.5% of seronegative women developed CIN, Since the risk associated with HPV-16 seropositivity (a measure of past or present in fection) was 35-fold lower than that of HPV DNA (present infection), m ost infections appear to be eliminated before CIN develops. In conclus ion, HPV 16 infection does confer an excess risk of CIN development, a nd HPV DNA detection has a high predictive value for the presence of h igh-grade CIN. (C) 1996 Wiley-Liss, Inc.