IMMUNOLOGICAL DIAGNOSIS AND MONITORING OF CERVICAL CANCERS USING IN-VITRO TRANSLATED HPV PROTEINS

E6 and E7 proteins, the transforming proteins of oncogenic HPVs, are known to be associated with the occurrence of cervical cancer. In radioimmunoprecipitation assays in which in vitro-transcripted and translated HPV-16 E6 and E7 proteins were used, patients with HPV-16-associated invasive cervical cancer (group I) had greater seroreactivity than patients in most of the other groups, including patients with invasive cervical cancer who were infected with other types of HPVs (group II), cervical cancer patients with nondetectable HPVs (group III), patients with HPV16-associated cervical intraepithelial neoplasia (group IV), and unaffected normal controls with noncervical lesions (group V) (P < 0.05). The sera of patients in group I, when compared with the sera of other groups, were significantly reactive with one and/or two proteins (P < 0.05). Antibodies to HPV-16 E6 and E7 proteins were detected in patients with invasive cancer more than in those with CIN. The positive rates for E6 protein were 4.2% (1/24), 43.8% (7/16), 57.1% (8/14), 100% (5/5), and 100% (1/1), and the positive rates of E7 protein were 4.2% (1/24), 12.5% (2/16), 35.7% (5/14), 60% (3/5), and 100% (1/1) from CINs through stages I, Ila, IIb, and III of HPV-16-associated cervical cancers, respectively. The positive rates for E6 and E7 proteins were significantly increased with the advancing of the clinical stages of cervical cancer (P < 0.05 for E6 and E7). To examine the change in antibody titers of HPV-16 E7 protein during diagnosis, treatment, and follow-up, we tested serial serum samples from 14 patients of group I. The antibody titers were correlated to the clinical course of disease in some cases. The positive levels of E7 antibody were decreased when the treatment was effective, but in 1 patient who had shown recurrence or progression, positive seroreactivity was maintained. Antibodies to HPV-16 E6 and E7 proteins might be effective virus-specific and disease state-specific markers of HPV-16-associated cervical cancer. (C) 1995 Academic Press, Inc.