Worldwide there is a strong relation between the presence of human papillomavirus (HPV) and the development of cervical cancer. This study investigated the prevalence and genotype of HPV in women with normal smears, women with premalignant lesions and women with cervical cancer in Antwerp, Belgium. Type-specific polymerase chain reaction (PCR) for HPV types 16 and 18 and general primer PCR (GP5+/6+) was performed on DNA extracted from paraffin-embedded tissue from women with lesions or fresh material from controls. HPV was detected in 11% of controls, 61% of women with atypia, 77% of women with CIN lesions and 88% of women with cervical carcinoma (chi2 trend, 273, p<0.001). The odds ratio for high-risk HPV types was 9.3 for atypia (95%CI. 4.3-19.8), 33.6 for CIN lesions (95%CI, 19.3-58.6) and 78.8 for cervical cancer (95%CI, 39.2-158.3). In total, 19 different HPV genotypes were detected, including five low risk HPV types. Seven of the 14 high-risk HPV types were detected in cervical cancer patients. Based on our study it is suggested that a prophylactic vaccine based on a cocktail of a limited number of high-risk HPV types should be considered in order to protect most women from developing cervical cancer.