Human Papillomavirus-Related Serological Markers of Invasive Cervical Carcinoma in Brazil

Masked sera from 194 cases and 217 controls participating in a case-control study of cervical cancer in Brazil were examined for antibodies to human papillomavirus (HPV) 16 E6 and E7 by radioimmunoprecipitation assay. Radiolabeled full-length E6 and E7 proteins expressed by in vitro transcription and translation in rabbit reticulocyte lysate were used as antigens. The antibody prevalences in cases and controls were: 54.1% versus 6% for E6; 30.4% versus 4.6% for E7; 63.4% versus 10.1% for either E6 or E7; and 21.1% versus 0.5% for both E6 and E7. The corresponding odds ratios were 35 ([95% confidence interval (CI)], 15-83), 10 (95% CI, 4-25), 28 (95% CI, 13-61) and 87 (95% CI, 10-736). The most marked contrast between cases and controls was observed for sera with high antibody titers (cpm > 6000) with an odds ratio of 239 (95% CI, 29-1946) for E6 or E7. Seroreactivity in cases was partially type specific; women who had HPV-16 DNA in the genital tract had higher antibody prevalence rates than those who were negative for HPV DNA. Reactivity to the E6 protein was associated with the stage of disease; the antibody prevalence was 62.7% in cases with stages II—IV and 31.0% in cases with stage I (P< 0.005). HPV-16 serology and HPV polymerase chain reaction were compared as markers for invasive cervical cancer. The sensitivity and specificity estimates were: 63.4% and 89.9% for HPV-16 serology; 53.8% and 94.9% for HPV-16 DNA; 84.4% and 82.7% for any HPV DNA; and 90.7% and 75.5% for a combination of HPV-16 serology and any HPV DNA. The specificity for high E6 or E7 titers was 99.5%. The HPV-16 E6 and E7 serological assays confirm the association of HP Vs with cervical cancer previously established by HPV DNA assays. The serological assays may be useful as an adjunct to pathological diagnosis and potentially of value for clinical management of HPV-associated cervical cancers.