HPV-16-RELATED PROTEINS AS THE SEROLOGIC MARKERS IN CERVICAL NEOPLASIA

Objective. Recently, a variety of HPV-related proteins have been synth esized and their utility as diagnostic and prognostic markers in cervi cal cancers needs to be assessed, The ability to generate preparative amounts of HPV-16 L1/L2 VLPs and E6, E7 proteins may have implications for the development of a serologic assay to detect anti-HPV-16 virion immune responses. The purpose of the study is to improve the way of p roper management of the cervical cancer by investigating the utility o f the recently developed HPV-16 L1/L2 VLPs, HPV-16 E6, E7 proteins as the clinical serologic markers through antibody reactions by compariso n with those of SCCA and CEA which have been used as tumor markers for cervical cancer. Methods. The serologic responses in Korean women wit h cervical neoplasia by ELISA using HPV-16 L1/L2 VLPs and radioimmunop recipitation assay (RIPA) using in vitro translated HPV-16 E6, E7 prot eins were investigated, PCR using E6 type-specific primers for HPV-16/ 18 was used to determine the presence and type of HPV infection (norma l controls, 15 cases; preinvasive lesions, 28 cases; invasive cervical cancers, 124 cases). Results. The sera of 34% (42/124) of cervical ca ncers were positive for SCCA and the sera of 18% (22/124) of cervical cancers were positive for CEA, The positivity of SCCA was increased wi th advancing clinical stages, but the antibody levels were not correla ted with clinical stage of disease. The sera of 7% (1/15) of normal co ntrols, 39% (11/28) of preinvasive lesions, and 56% (70/124) of patien ts with cervical cancer were ELISA positive for HPV-16 L1/L2 VLPs (P < 0.05), The sera of 7% (2/28) of preinvasive lesions and 51% (63/124) of cervical cancers were positive for in vitro translated HPV-16 E6 pr otein (P < 0.05) and the sera of 11% (3/28) of preinvasive lesions and 33% (41/124) of cervical cancers were positive for in vitro translate d HPV-16 E7 protein (P < 0.05), The antibody levels to HPV-16 E7 prote in were correlated to clinical stage and tumor burden in a significant number of cervical cancers. Conclusions. These data suggest that a co nsiderable number of patients with cervical neoplasia generated positi ve antibody response to L1/L2 VLPs and in vitro translated E6, E7 prot eins of HPV-16, These HPV-16-associated proteins might be disease-spec ific markers which could be useful in an adjunctive diagnostic assay a nd a seroepidemiologic study of HPV-related cervical neoplasia. In par ticular, the monitoring of antibody to HPV-16 E7 protein seems to be v aluable in the proper management of cervical cancers for specific tumo r markers. (C) 1998 Academic Press.