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

E6 and E7 proteins, the transforming proteins of oncogenic HPVs, are k nown to be associated with the occurrence of cervical cancer. In radio immunoprecipitation assays in which in vitro-transcripted and translat ed HPV-16 E6 and E7 proteins were used, patients with HPV-16-associate d invasive cervical cancer (group I) had greater seroreactivity than p atients 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), patient s 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 prote ins (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 posi tive 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 wer e 4.2% (1/24), 12.5% (2/16), 35.7% (5/14), 60% (3/5), and 100% (1/1) f rom CINs through stages I, Ila, IIb, and III of HPV-16-associated cerv ical 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 diseas e in some cases. The positive levels of E7 antibody were decreased whe n the treatment was effective, but in 1 patient who had shown recurren ce or progression, positive seroreactivity was maintained. Antibodies to HPV-16 E6 and E7 proteins might be effective virus-specific and dis ease state-specific markers of HPV-16-associated cervical cancer. (C) 1995 Academic Press, Inc.