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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/553

Title: EVALUATION OF SEROLOGICAL RESPONSE TO ONCOPROTEINS OF HUMAN PAPILLOMAVIRUS TYPES 16 AND 18 AS POTENTIAL SEROMARKERS FOR CERVICAL CANCER SCREENING
Authors: LIKU, BEKELE
Advisors: Dr. Yohannes Mengistu
Dr. Abraham Aseffa
Dr. Howard Engers
Keywords: ELISA
GST fusion protein
HPV
Cervical cancer
Copyright: 2005
Date Added: 17-Apr-2008
Publisher: Addis Ababa University
Abstract: Cervical cancer is a serious public health problem of global importance. Nearly 80% of the half-a-million new cases reported annually occur in developing countries. The rate of cervical cancer in Ethiopia is estimated to be as high as 32% of all female malignancies diagnosed in hospitals. Over 90% of cervical cancer is attributable to certain HPV infections. HPV -16 and -18 have been recognized as the first and the second most common HPV genotypes in all regions, and were detected in 74% of all cases globally. The recognition that infection with HPV is essential for the development of cervical cancer has led to the development not only of HPV vaccines, but also of cervical cancer screening strategies that incorporate HPV testing. For Ethiopia to benefit from these developments, epidemiological surveys of HPV prevalence and knowledge of the immune response patterns to HPV proteins with diagnostic potential is fundamental. In this study, we investigated whether antibody response to selected oncoproteins of the two most frequent HPV types could serve as screening assay for invasive cervical cancer. We recruited 271 cervical cancer patients and 107 women with different non-cervical cancer disease conditions from the gynaecologic outpatient clinics of a tertiary level university hospital. We obtained fresh biopsy specimens from cervical cancer cases and blood from all the study participants. Antibodies against E6, E7 and L1 proteins of HPV-16 and -18 in plasma were determined using ELISA that uses glutathione-casein conjugate to capture recombinant protein antigens fused to glutathione S-trasnferase. HPV DNA detection and typing was done by L1 consensus PCR with PGMY09/011 biotinylated primers followed by hybridisation to a line blot. A strong association of E6 and/or E7 with cervical carcinoma was observed among Ethiopian cervical cancer patients as well, with 72.7% positives in the cases and 14.9% in the controls (OR=12.8,95% CI 6.2-26.4) (p<0.001). Antibodies against HPV-16 L1 were also associated with cervical cancer (OR=2.6, 95% CI 1.4-4.8). Antibody responses to E6 and E7 were dependent on the clinical stage of the disease, with 38.5% positives in FIGO Stage 0, 57.1% in Stage I and reaching to 83.5% in Stage III (p<0.05). There was no correlation between antibody response to HPV-16 E6 and E7 oncoproteins and antibodies against HPV-16 L1 capsid protein. The HPV serological assays were also compared as screening/diagnostic tests for invasive cervical cancer. The sensitivity estimates were 72% and 73% for E6 and/or E7 ELISA and E6, E7 and L1 ELISA in combination, respectively. x Specificity estimates were highest for E7 oncoprotein based ELISA (96.3%). A similar pattern was observed, with regard to the detection of the genotype of HPV present in the tumour. The HPV-16 E6, E7 and L1 ELISA combined were able to detect the type of HPV DNA in 30/32 patients with HPV-16 positive tumour. These data suggest that antibodies against E6, E7 and L1 protein are good candidates for use as markers of cervical HPV infections and the detection of invasive cervical cancer in settings where cytology–based tumour screening is not available. These serological diagnostic techniques could also offer alternatives to the generally expensive cell/tissue requiring DNA based technologies generally in use for population based epidemiological surveys on HPV.
Description: A THESIS SUBMITTED TO GRADUATE PROGRAMME OF ADDIS ABABA UNIVERSITY IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTERS OF SCIENCE IN MEDICAL MICROBIOLOGY
URI: http://hdl.handle.net/123456789/553
Appears in:Thesis - Medical Microbiology

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