ANTIBODIES AGAINST EARLY PROTEINS OF HUMAN PAPILLOMAVIRUSES AS DIAGNOSTIC MARKERS FOR INVASIVE CERVICAL-CANCER

Cervical cancer is the most prevalent tumor in developing countries an d the second most frequent cancer among females worldwide, Specific hu man papillomaviruses (HPVs) and, most notably, HPV types 16 and 18 are recognized as being causally associated with this malignancy. Antibod ies against early HPV proteins E6 and E7 have been found more often in patients,vith tumors than in controls. Existing peptide enzyme-linked immunosorbent assays (ELISAs) for the detection of anti-E6 and anti-E 7 antibodies in human sera have low levels of sensitivity and specific ity and thus are not suitable for use as diagnostic tools. Based on hi ghly purified recombinant native proteins, we developed four sandwich ELISAs for the detection of antibodies against HPV type 16 and 18 E6 a nd 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-pos itive patients, the HPV type indicated by seroreactivity was identical to the HPV DNA type found in the tumor, which also indicates a high d egree of specificity for antibody detection with respect to HPV type, In a direct comparison of 72 serum specimens from patients,vith cervic al cancer, 56% of the specimens reacted in at least one of the four pr otein ELISAs, whereas 40% reacted in at least one of seven peptide ELI SAs covering the four antigens. These assays could be of value for the detection of invasive cervical cancer in settings in which cytology-b ased early tumor screening is not available, for the clinical manageme nt of patients diagnosed with cervical cancer, and for the immunologic al monitoring of E6 and E7 vaccination trials.