Page 76 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

Chapter 3
alleles.[8, 20] Further research in larger populations should focus on this issue. A final limitation may be that we did not specify the HLA-DRB1*13 allele further. Whereas Sastre-Garau et al. studied the correlation of the HLA-DRB1*13 allele and spontaneous regression, Matsumoto et al. focused on the HLA-DRB1*13:02 allele.[9, 10] Other studies show that the protective effect of HLA- DRB1*13 appeared to be contributed by individual alleles: HLA-DRB1*13:01, *13:02 and *13:03.[7, 19] Studying the overall HLA-DRB1*13 allele group may therefore mask the protective effects of individual alleles. The limited availability of DNA material in our study, however, did not facilitate further specification of individual alleles.
In conclusion, we found no effect of the HLA repertoire on spontaneous regression of high-grade CIN in the current patient group and could therefore not identify HLA alleles as a prognostic biomarker in high-grade CIN. We did find a protective effect of the HLA-DRB1*13/14 allele group against HPV16 induced high-grade CIN. Given the established fact that HLA-DRB1*13 is protective against CIN and cervical cancer and has been shown to induce spontaneous regression of low- grade CIN, we hypothesize that the protective effect of HLA-DRB1*13 is exerted by preventing the development of high-grade lesions, rather than promoting spontaneous regression of these lesions. This protective effect may be exerted through an enhanced immune response to HPV16. Further research is necessary to test our hypothesis and to establish the mode of action of this protective effect.
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