The objectives of this study were to confirm the hypothesis that invasive carcinoma of the uterine cervix and the precursors of that condition are most often caused by human papilloma virus (HPV) infections, and to determine whether or not other risk factors are involved in the neoplastic process. For this purpose, four concurrent case-control studies were carried out. Two included cases of invasive cervical cancer and population-based controls. The other two included cases of in situ carcinoma and controls. Research was carried out in nine provinces of Spain and in Cali, Colombia. The identification of cases took place between June 1985 and June 1988. The studies included 436 incident cases of invasive carcinoma and 387 controls, selected at random from the corresponding populations, and 525 cases of in situ carcinoma and 512 controls paired by age, place of recruitment, and date that cytological specimens were taken from the women participating in cytological screening programs. Exposure to HPV was detected through hybridization tests after amplification by polymerase chain reaction (PCR) in exfoliated cervical cells from cases and controls. Exposure to HPV was the principal risk factor in the four studies. For invasive carcinoma, the relative risk and 95% confidence interval were 46.2 (18.5-115.1) in Spain and 15.6 (6.9-34.7) in Colombia. For in situ carcinoma, the figures were 56.9 (24.8-130.6) in Spain and 15.5 (8.2-29.4) in Colombia. This strong association was specific for types 16, 18, 31, 33, and 35 as well as still-unclassified HPV types.(ABSTRACT TRUNCATED AT 250 WORDS)