Page 74 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

Chapter 3
HLA repertoire and HPV status
A significant association was found between HLA-DRB1*13/14 alleles and HPV status. The lesions of all eight patients with an HLA-DRB1*13/14 allele were HPV16-negative, while the lesions of patients without an HLA-DRB1*13/14 allele were equally frequent HPV16 positive (n=12) as HPV16 negative (n=12) (p=0.0135). Results are presented in table 3. There was a trend towards HPV16 negativity in patients with an HLA-DRB1*13 allele: all six patients with an HLA-DRB1*13 allele were HPV16-negative. Of those patients without an HLA-DRB1*13 allele, 12 were HPV16 positive and 14 were HPV16 negative (p=0.0613). No other significant associations were found between other HLA alleles and HPV status.
Table 3. HLA-DRB1*13/14 in relation to HPV status in high-grade CIN lesions
HPV 16 0 12 0 12 0 12 Others6 14 2 18 8 12
p=0.0613 p=0.5161 p=0.0135
Discussion
The results of this study show a potential protective effect of the HLA-DRB1*13/14 allele group against HPV16 positive CIN, suggesting a common epitope in the DRB1*13/14 allele group. None of the women with an HLA-DRB1*13/14 allele group had an HPV16 positive CIN lesion. In our cohort, no correlation of any HLA-A, -B, -C, -DRB1 or -DQB1 alleles with spontaneous regression of high-grade CIN was observed.
Previous publications found significant influences of certain HLA types on the spontaneous regression of both low- and high-grade CIN lesions. In low-grade lesions, HLA-DRB1*13 has been associated with spontaneous regression and HLA-DRB1*13:02 was found to protect against progression to CIN 3.[9, 10, 14] Only one study has described the influence of the HLA repertoire on the spontaneous regression of high-grade CIN lesions. In this study, women with an HLA-A*02:01 allele were significantly less likely to clear a CIN 2/3 lesion than women without this allele (14.3% vs 42.3%, p=0.05), but only in HPV16 negative lesions.[4] The influence of HLA- DRB1*13 on spontaneous regression in high-grade CIN lesions was not assessed in this study. Our study did not show a protective effect of HLA-DRB1*13 in high-grade CIN lesions. Neither could we confirm the previously established association between the HLA-A*02:01 allele and the natural history of high-grade CIN lesions. This could be caused by the limited number of patients in our study. However, the lack of a protective effect of HLA-DRB1*13 in high-grade CIN lesions represented in our cohort may also be explained by the possibility that the protective effect of the HLA-DRB1*13 allele against cervical carcinoma occurs in the early stages of CIN, and not in the stage of established CIN3 lesions or lesions progressing to cervical cancer. Rather, the HLA- DRB1*13 allele may be protective against the development of high-grade CIN in the first place. This theory is supported by population frequency studies, showing a similar frequency of the HLA-DRB1*13 allele in patients with low-grade lesions as compared to the general population,
DRB1*13
No DRB1*13
DRB1*14
No DRB1*14
DRB1*13/14
No DRB1*13/14
72