Cervical cancer is the world's fourth most frequent malignancy within the female population. Despite the established screening, incidences in the Czech Republic occur at a rate of about 20 cases per 100,000 women and with a mortality rate around 9 out of 100,000 women. The main factor of dysplasia and subsequent cervical cancer is the chronic infection with the human papillomavirus. This occurs when the oncogenic HPV types inactivate regulatory proteins of a cell and leads to uncontrolled cell proliferation. The aim of this study was to evaluate the benefits of immunochemical methods in the diagnostics of HPV infection in dispensarized patients with a finding of various grades of dysplasia. Immunocytochemical and immunohistochemical methods with an inhibitor of cyclin-dependent kinase p16INK4a and nuclear proliferation marker Ki-67 were used in a sample survey group of 47 women. The sample groups were also tested for the presence of the highly oncogenic HPV types by Hybrid Capture 2 method, but the relationship of the viral load and the grade of dysplasia was not proven. The control group consisted of five patients with normal findings, where the expected negativity of studied markers was confirmed. The results showed a correlation between the expression of the protein p16INK4a in cytological preparations with the morphological manifestations of the HPV infection in histological preparations, particularly with higher grades of dysplastic changes. This work confirmed that the detection of specific markers in the cytological and biopsy material contributes significantly to the specification of the degree of precancerous lesions on the cervix and, thus, their early detection.
Various high-risk HPV (hr HPV) DNA assays have been developed that allow detection of a broad spectrum of HR HPVs. Two of these assays [Hybrid Capture 2 (hc2) and GP5+/6+-PCR] have shown in large clinical trials a superior clinical sensitivity for cervical (pre)cancer compared to cytology and an optimal balance between clinical sensitivity and pecificity. Comparative studies showed that an increased sensitivity for HR HPV relative to GP5+/6+-PCR and/or hc2 results in a dramatic decrease in clinical specificity, whereas on the other hand a decreased sensitivity for virus leads to a decrease in sensitivity for (pre)cancer. These data argue for guidelines on HR HPV test requirements for cervical screening purposes.
- MeSH
- diagnostické techniky molekulární metody využití MeSH
- dysplazie děložního hrdla diagnóza etiologie imunologie MeSH
- hybridizace in situ metody normy využití MeSH
- infekce papilomavirem diagnóza imunologie MeSH
- lidé MeSH
- nádory děložního čípku diagnóza etiologie imunologie MeSH
- plošný screening metody normy využití MeSH
- polymerázová řetězová reakce metody normy využití MeSH
- prekancerózy diagnóza etiologie imunologie MeSH
- Check Tag
- lidé MeSH
This study evaluates the association of antibodies against HPV-16-derived peptides with cervical cancer and estimates the sensitivity and specificity of the serological assays in relation to HPV DNA detection in cervical cells by PCR. Study subjects were derived from 4 case-control studies carried out in Spain and Colombia. Sera from 544 cases of CIN III and invasive cancer and of 543 age-matched controls were tested for antibodies to 5 peptides derived from E2, E7 (3 partially overlapping frames of HPV 16 denoted E7/ 1, E7/2, E7/3) and L2 open reading frames of HPV 16. HPV DNA was detected using a L1-PCR based method. Among cancer controls, antibody response to E2 and E7/1, E7/2, E7/3 was higher in Colombia (22.5%,7.2%,11.7%,12.6% respectively) than in Spain (17.1 %, 4.7%, 5.9%, 5.9%). E7 antibodies were related to stage, particularly in CIN III vs. invasive stages and less markedly within invasive stages. Detection of antibodies to the E7/1 was associated to CIN III (OR = 1.8). The risk of invasive cervical cancer was increased among those with antibodies to E2 (OR = 2.2), to E7/1 (OR = 4.2), to E7/2 (OR = 4.3), and to E7/3 (OR = 2.5). Presence of antibodies to all the 3 E7 peptides increased the risk of CIN III (OR = 5.6) and that of invasive cancer (OR = 17.5). High levels of antibodies to E7/1 or E7/2 or E7/3 increased the risk of invasive cervical cancer (OR for high levels of antibodies vs. negatives to E7/1 OR = 22.6; E7/2 OR = 7.5, E7/3 OR = 3.4). In the present analysis, antibodies to L2 were not associated with either CIN III or cervical cancer. Serological markers of HPV 16 detected less than half of the HPV-16-DNA-positive cases. It is concluded that antibodies to E2 and particularly E7 antigens are strongly associated with cervical cancer. Antibodies to E7 seem to be a moderate marker of tumor burden.
- MeSH
- antigeny virové imunologie MeSH
- dospělí MeSH
- dysplazie děložního hrdla * imunologie MeSH
- karcinom in situ imunologie mikrobiologie MeSH
- karcinom * imunologie mikrobiologie MeSH
- lidé MeSH
- nádory děložního čípku * imunologie mikrobiologie MeSH
- Papillomaviridae * imunologie MeSH
- protilátky virové * imunologie MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Geografické názvy
- Kolumbie MeSH
- Španělsko MeSH
- MeSH
- dysplazie děložního hrdla imunologie MeSH
- imunologické faktory MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
