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Journal of Clinical Microbiology, February 1998, p. 475-480, Vol. 36, No. 2
Angewandte Tumorvirologie, Deutsches
Krebsforschungszentrum, D-69120 Heidelberg,
Germany1;
Instituto Mexicano del
Seguro Social, Hospital de Oncología, Unidad de
Investigacion, C.P. 06741 Mexico City,
Mexico2; and
Tanzania Tumor Center,
Ocean Road Hospital, Dar es Salaam, Tanzania3
Received 2 July 1997/Returned for modification 17 September
1997/Accepted 5 November 1997
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.
0095-1137/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Antibodies against Early Proteins of Human
Papillomaviruses as Diagnostic Markers for Invasive Cervical
Cancer
*
Corresponding author. Mailing address: Angewandte
Tumorvirologie, Abteilung 0615, Deutsches Krebsforschungszentrum,
Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany. Phone: (49)
6221-424645. Fax: (49) 6221-424932. E-mail:
M.Pawlita{at}dkfz-heidelberg.de.
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