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Biomedical subjects

L Benitez-Bribiesca

Publications and source records attributed to L Benitez-Bribiesca.

7 recordsLinked to original sources

Antibodies against early proteins of human papillomaviruses as diagnostic markers for invasive cervical cancer.

Cervical cancer is the most prevalent tumor in developing countries and the second most frequent cancer among females worldwide. Specific human papillomaviruses (HPVs) and, most notably, HPV types 16 and 18 are recognized as being causally associated with this malignancy. Antibodies against early HPV proteins E6 and E7 have been found more often in patients with tumors than in controls. Existing peptide enzyme-linked immunosorbent assays (ELISAs) for the detection of anti-E6 and anti-E7 antibodies in human sera have low levels of sensitivity and specificity and thus are not suitable for use as diagnostic tools. Based on highly purified recombinant native proteins, we developed four sandwich ELISAs for the detection of antibodies against HPV type 16 and 18 E6 and E7 proteins. We demonstrate their sensitivities and high degrees of specificity for cervical cancer. Among a total of 501 serum specimens from unselected patients with invasive cervical cancer, 52.9% reacted positively in at least one of the four assays. In contrast, among 244 serum specimens from control subjects without cervical cancer, only 2 reactive serum specimens (0.8%) were found. For 19 of 19 antibody-positive patients, the HPV type indicated by seroreactivity was identical to the HPV DNA type found in the tumor, which also indicates a high degree of specificity for antibody detection with respect to HPV type. In a direct comparison of 72 serum specimens from patients with cervical cancer, 56% of the specimens reacted in at least one of the four protein ELISAs, whereas 40% reacted in at least one of seven peptide ELISAs covering the four antigens. These assays could be of value for the detection of invasive cervical cancer in settings in which cytology-based early tumor screening is not available, for the clinical management of patients diagnosed with cervical cancer, and for the immunological monitoring of E6 and E7 vaccination trials.

Adult↗

Therapeutic uterine-cervix cancer vaccines in humans.

Infection with high-risk human papillomavirus (HPV) types is involved in early stages of uterine=cervix cancer development. The virally encoded E6 and E7 oncoproteins behave as tumor-specific antigens and represent targets for a vaccine designed to control HPV-induced tumors. Using either proteins or peptides based on E6 and E7 oncoproteins of HPV16 and 18, phase I clinical trials of therapeutic vaccines against HPV-associated cervical cancers have recently been reported. Although the effectiveness of these vaccines cannot be evaluated in such small studies, they constitute an important step toward the development of therapeutic uterine=cervix cancer vaccines. A polytope DNA vaccination approach combined with immunomodulatory cytokines may offer an excellent strategy to reduce the risk of relapse and metastasis following conventional therapies.

Animals↗

The association of human papillomavirus type 16 E6 and E7 antibodies with stage of cervical cancer.

OBJECTIVE: Previous investigators have reported higher HPV type 16 antibody positivity among cervical cancer patients than among healthy women. The objective of this study was to determine the association of HPV 16 antibody levels with the stage of cervical cancer. METHODS: Pretreatment tumor biopsies and sera were obtained from 137 newly diagnosed cervical cancer patients residing in Mexico. Using peptide ELISA and radioimmunoprecipitation assay (RIPA), HPV 16 E6- and E7-specific antibodies were measured. RESULTS: By ELISA, elevated antibody titers to HPV 16 E6 and E7 were detected in 16.8 and 32.8% of the women, respectively. While sera positivity did not differ by disease stage, the mean absorbance in the E7-positive sera was 0.42, 0.62, 0.91, and 0.81 for stages I to IV, respectively. Using RIPA, anti-E6 and E7 positivity was demonstrated in 46.7 and 38.7% of the females, respectively. Although no difference across disease stage was detected for E6, increasing proportions of positivity to E7 with stage of disease was detected. The rates for increasing disease stage were 0.14, 0.37, 0.40, and 0.67. Sera from the 6-month postradiation follow-up examinations of a small group of patients demonstrated a statistically significant decrease in antibody positivity from pretreatment positivity to HPV 16 E6 (n = 14; P = 0.01) and HPV 16 E7 (n = 20; P = 0.0001) using ELISA. CONCLUSIONS: These data suggest that HPV 16 E7 antibody positivity may be associated with stage of cervical cancer. Such immune parameters may be applicable to disease staging, monitoring of recurrence and, perhaps, diagnosis. Further investigation into the relationship of HPV 16 E6 and E7 antibodies with stage of cervical cancer and response to therapy is warranted.

Adult↗

Antibodies against linear and conformational epitopes of the human papillomavirus (HPV) type 16 E6 and E7 oncoproteins in sera of cervical cancer patients.

Sera obtained from 137 cervical cancer patients were analysed for the presence of antibodies to the human papillomavirus (HPV) type 16 proteins E6 and E7 by the aid of different assays, i.e. ELISA using as antigen either synthetic peptides or the complete E7 protein and radio-immunoprecipitation (RIPA) which uses the viral protein made by in vitro transcription/translation. In agreement with previous reports, reactivity to the E7 protein was found more frequently than to the E6 protein (31.4% vs. 16.8%) when the sera were assayed by peptide-based ELISA. In contrast, when RIPA was employed, reactivity to either protein was obtained at similar frequency (38.7% vs 46.7%). When the protein was denatured prior to immuno-precipitation the reactivity was lost in all sera tested for E6-specific antibodies but only in a few samples in the E7-RIPA. Therefore it was concluded that the increased sensitivity of the E6-RIPA as compared to the E6 peptide-ELISA is due to the detection of antibodies to conformational epitopes which are presented by the in vitro product but not by the synthetic peptides. Eighty-two sera from healthy donors were tested by HPV 16E6- and E7-RIPA and also by ELISA using the HPV 16E7 protein which was produced in the fission yeast Schizosaccharomyces pombe. One sample reacted each in the E6- and E7-RIPA indicating a high specificity of these assays. The E7 protein-ELISA proved to be less sensitive for the detection of antibodies in cervical cancer patients' sera (22.6% positive) as compared to peptide-based ELISA or RIPA.

Adolescent↗