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Background and Objectives: Strong epidemiologic evidence indicates that human papillomavirus (HPV) is the main etiologic factor of cervical cancer. A few cohort studies suggest that most HPV infections are transient in young women and that persistent HPV infections are more common in older women. Little is known about the determinants of persistent HPV infections. The present study was aimed at increasing our knowledge about these determinants., Goals: To identify risk factors for genital HPV DNA detection among cytologically normal middle-aged women., Study Design: Eight hundred ten women who participated as control subjects in three case-control studies on cervical cancer in Spain, Colombia, and Brazil were included in this study. After an interview, women underwent a gynecologic examination with collection of exfoliated cells for a Papanicolaou smear and HPV DNA detection. Human papilloma virus DNA was detected by polymerase chain reaction (PCR)-based hybridization techniques., Results: The HPV positivity rate was 10.5% in the whole population, but was higher in the areas with high incidence of cervical cancer (17% in Brazil and 13% in Colombia) than in Spain (4.9%), which is a low-risk area for cervical cancer. Age was related to the prevalence of HPV DNA in Brazil, but not in Spain and Colombia. In univariate analyses in all three countries, the prevalence of HPV DNA was positively associated with the number of lifetime sexual partners and inversely associated with the levels of family income and with age at first sexual intercourse. There was four times increase in the odds ratio (OR) of HPV infection in women who had six or more lifetime sexual partners compared with those with one or less. The use of any kind of contraceptive tended to decrease the OR for HPV detection. Their ORs ranged from 0.44 (barrier methods) to 0.48 (oral contraceptives). In Spain and Colombia, antibodies against Chlamydia trachomatis were positively associated with the prevalence of HPV DNA. In a final multivariate model, the positive associations with lifetime number of sexual partners, socioeconomic status, and C. trachomatis persisted., Conclusions: These results support the sexual transmission of HPV and suggest that socioeconomic status and antibodies to C. trachomatis are independent predictors of HPV detection in middle-aged cytologically normal women.

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)

To evaluate the association between human papillomavirus (HPV) and cervical cancer, we performed a population-based case-control study in Columbia and Spain, the former country having an incidence rate of cervical cancer about 8 times higher than the latter. It included 436 cases of histologically confirmed invasive cervical cancer and 387 randomly selected population controls. Information on demographic variables, sexual behaviour and other risk factors was obtained by interview. HPV-DNA was measured in cervical-swab specimens with 3 hybridization assays: ViraPap, Southern hybridization (SH) and polymerase chain reaction (PCR). The presence of HPV-DNA and detection of types 16, 18, 31, 33 and 35 were strongly associated with cervical cancer in each country regardless of the assay used. For both countries combined the adjusted odds ratios and 95% confidence intervals were: ViraPap OR = 25.9 (10.0-66.7); SH OR = 6.8 (3.4-13.4); and PCR OR = 28.8 (15.7-52.6). HPV-16 was the most common type detected in both cases and controls. Our results indicate that there is a very strong association between HPV 16, 18, 31, 33 and 35 and invasive cervical cancer and that this association is probably causal.

In order to provide a reliable diagnosis for the presence and type of human papillomavirus (HPV) DNA in a case-control study of cervical cancer in Colombia and Spain, 926 cervical scrapes from female subjects were examined by ViraPap (VP) and Southern hybridization (SH), and 510 of these (263 cases and 247 controls) were also tested by polymerase chain reaction (PCR) using the HPV L1 consensus primers. HPV DNA prevalence was much higher in cases than in controls by each of the three tests. There was complete agreement between the results of the three tests for 64.9% of the 510 specimens; 53.5% were negative and 11.4% were positive (regardless of type) by all tests. An additional 29.0% of the specimens were positive by PCR: 19.4% by PCR alone, 6.7% by PCR and VP, and 2.9% by PCR and SH. SH and/or VP gave positive results for 6.0% of the specimens for which the PCR finding was negative: 2.7% by SH alone, 2.5% by VP alone, and 0.8% by both VP and SH. When specimens which were positive by VP alone or only by SH at low-stringency conditions were excluded, PCR confirmed all but four specimens which were positive by other tests. The concordance between type-specific diagnosis by SH and PCR was 86% when HPVs were typed in both tests. HPV-16 accounted for over 80% of the typed HPVs in each test. The presence of blood in case specimens did not appear to inhibit HPV positivity by VP or by PCR at the dilution tested. Low amounts of cellular DNA of specimens resulted in some underestimation of HPV positivity by VP and SH but not by PCR. Compared with that of PCR, the sensitivities for case specimens were 38% by SH and 50% by VP; the sensitivity for control specimens, although it could not be measured precisely because there were few positive specimens, appeared to be lower than for case specimens. It was concluded that PCR-based tests are best suited for epidemiological investigation of HPVs.