HUMAN PAPILLOMAVIRUS - THE MOST SIGNIFICANT RISK DETERMINANT OF CERVICAL INTRAEPITHELIAL NEOPLASIA

Sexual behavior has been consistently identified as a major risk facto r for cervical cancer. Population-based studies have demonstrated that risk related to sexual activity is mediated by human papillomavirus ( HPV) infection. We conducted a case-control study of 199 cases with lo w-grade squamous intraepithelial lesions or high-grade squamous intrae pithelial lesions as defined by cytology and 1000 control women select ed from an ongoing prospective cohort study in Copenhagen, Denmark. Fu rthermore, 131 women with equivocal smears (atypical squamous cells of undetermined significance) were examined as a separate borderline cas e group. At enrollment, all women had a personal interview and a gynec ological examination including cervical swabs for HPV testing and a Pa p smear. HPV testing was performed using a combination of general prim er 5/6-mediated and type-specific polymerase-chain-reaction-based meth ods. Cervical HPV infection was by far the most significant risk facto r for cervical squamous intraepithelial lesions. The relationship with HPV was observed for all grades, while strength of association was gr eater for more severe lesions. The importance of the previously identi fied epidemiological risk factors for cervical neoplasia was also demo nstrated. However, most of the effect of these factors could be explai ned by taking HPV infection into account, except for schooling and smo king. Non-use of barrier contraceptives and smoking were the only sign ificant risk factors in HPV-positive women. In HPV-negative women, a r esidual effect existed for different measures of sexual activity, and use of oral contraceptives and smoking constituted significant risk de terminants. Overall, 66% of cases could be attributed to HPV; however, if the results were restricted to histologically confirmed high-grade lesions, the proportion of cases that could be attributed to HPV infe ction increased to 80%. (C) 1996 Wiley-Liss, Inc.