Antibodies against high-risk human papillomavirus proteins as markers for invasive cervical cancer.

Different human papillomavirus (HPV) genes are expressed during the various phases of the HPV life cycle and may elicit immune responses in the process towards malignancy. To evaluate their association with cervical cancer, antibodies against proteins from HPV16 (L1, E1, E2, E4, E6 and E7) and HPV18/31/33/35/45/52/58 (L1, E6 and E7) were measured in serum of 307 invasive cervical cancer cases and 327 controls from Algeria and India. Antibody response was evaluated using a glutathione S-transferase-based multiplex serology assay and HPV DNA detected from exfoliated cervical cells using a GP5+/6+-mediated PCR assay. Among HPV16 DNA-positive cases, seroprevalence of HPV16 antibodies ranged from 16% for HPV16 E1 to 50% for HPV16 E6 and all were significantly higher than controls. Seroprevalence of E6, E7 and L1 antibodies for HPV18 and for at least one of HPV31/33/35/45/52/58 were also higher in cases positive for DNA of the corresponding type (50% and 30% for E6 of HPV18 and HPV31/33/35/45/52/58 combined, respectively). E6 and E7 antibodies were rarely found in controls, but cross-reactivity was evident among cancer cases positive for DNA of closely phylogenetically-related HPV types. E6 or E7 antibodies against any of the eight HPV types were detected in 66.1% of all cervical cancer cases, as compared to 10.1% of controls. E6, and to a lesser extent E7, antibodies appear to be specific markers of HPV-related malignancy. However, even among cases positive for the same type of HPV DNA, approximately one-third of cervical cancer cases show no detectable immune response to either E6 or E7.

Combes JD ，Pawlita M ，Waterboer T ，Hammouda D ，Rajkumar T ，Vanhems P ，Snijders P ，Herrero R ，Franceschi S ，Clifford G ... -  《-》

Antibodies against oncoproteins E6 and E7 of human papillomavirus types 16 and 18 in cervical-carcinoma patients from Russia.

Zumbach K ，Kisseljov F ，Sacharova O ，Shaichaev G ，Semjonova L ，Pavlova L ，Pawlita M ... -  《INTERNATIONAL JOURNAL OF CANCER》

Profiling of serum antibodies against human papillomavirus antigens in Korean women with cervical intraepithelial neoplasia and cervical cancer.

Sero-epidemiological studies of human papillomavirus (HPV) have been undertaken over the last two decades. In this study, the prevalences of nine serum antibodies (anti-E6, E7 and L1 antibodies of HPV types 16, 18, and 58) were evaluated in normal (control) Korean women and women with cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III, and cervical cancer. The frequencies of all types of anti-HPV antibodies were higher in the CIN stages and cervical cancer than in normal women, and those of anti-HPV16 E6 and E7, anti-HPV18 E6 and E7, and anti-HPV58 E7 antibodies were higher in the cervical cancer group than in the CIN stages. The frequencies of antibodies against HPV16, 18, and 58 E7 tended to increase with increasing severity of cervical lesions. However, there were few differences in the frequencies of antibodies against the L1 antigens of HPV16, 18 and 58 in cervical cancer versus CIN stages. The anti-HPV antibodies were detected in 26.5% of normal, 46.3% of CIN I, 62.5% of CIN II, 51.6% of CIN III, and 75% of cancers when any of the nine antigens was used as a criterion. Correlations between HPV DNA positivity and seropositivity for anti-HPV E6, E7, or L1 antibodies were found only in HPV16 DNA-positive cervical cancers for anti-HPV16 E6 and L1 antibodies. In addition, strong positive correlations in seropositivity were found between anti-HPV16 E7 and anti-HPV58 E7 antibodies, and between anti-HPV18 E6 and anti-HPV58 E6 antibodies. These findings should advance global profiling of the seroprevalences of antibodies against HPV antigens.

Jin Y ，Choi JW ，Kim HJ ，Eddouzi J ，Kim SC ，Ju W ，Kim YH ，Kim HJ ... -  《Cancer Medicine》

Antibodies against human papillomavirus (HPV) type 16 and 18 E2, E6 and E7 proteins in sera: correlation with presence of papillomavirus DNA.

Human papillomavirus (HPV) infection is associated with cervical cancer. The E2 and E1 papillomavirus proteins are expressed at the early stage of infection and regulate DNA replication. The E2 protein activates and represses transcription from different HPVs promoters. At some stage when viral DNA gets integrated into the cellular genome, the E2 gene is disrupted or inactivated. This event leads to a derepression of the E6 and E7 viral oncogenes. These viral proteins are required normally for the maintenance of the malignant phenotype. Therefore, the E2, E6, and E7 proteins are present in all patients infected by papillomavirus. In this study, the association of antibody levels against E2, E6, and E7 proteins of HPV types 16, 18, and 6 was determined in relation to the presence of HPV DNA at the initial stages of HPV infection. Serum samples from 172 women with HPV infection, determined by Papanicolau (Pap) smears and colposcopy, were tested. Elevated antibody titers against E2 protein from the HPV 6 and HPV 16 were detected in 46.42 and 66.96% of the patients, respectively. Antibodies against the E7 and E6 proteins of HPV 16 were found in 51.78 and 36.60% of the patients, respectively. Antibodies against the E6 and E7 proteins of HPV 18 were 35 and 45%, respectively. A statistical difference was found for antibody titers against the E2, E6, and E7 proteins between patients with papillomavirus DNA and controls cases who had no cytological abnormalities and no HPV DNA. Sera titers were 1/500 for patients HPV positive and 1/50 for control individuals. Antibodies titers against E6 and E7 proteins were also examined in patients at 6 and 24 months after cryosurgery. In these patients, a slight decrease in the antibody level against the E2, E6, and E7 proteins was found. No correlation was found between age and number of sexual partners, with serum positivity to the E2, E6, and E7 papillomavirus proteins. These data suggest that antibodies against the E2, E6, and E7 proteins are good candidates for use as markers for monitoring cervical HPV infections.

Rosales R ，López-Contreras M ，Cortes RR 《JOURNAL OF MEDICAL VIROLOGY》

HPV-16-related proteins as the serologic markers in cervical neoplasia.

Park JS ，Park DC ，Kim CJ ，Ahn HK ，Um SJ ，Park SN ，Kim SJ ，Namkoong SE ... -  《GYNECOLOGIC ONCOLOGY》