Page 71 - Strategies for non-invasive managementof high-grade cervical intraepithelial neoplasia - prognostic biomarkers and immunotherapy Margot Maria Koeneman

The required test performance values include a high specificity and positive predictive value:
lesions that will not regress spontaneously must be identified, as treatment is necessary in these
women. The actual values depend on the follow-up term of observational management. Lower
values can be accepted when strict histological follow-up is implemented to identify persisting
lesions at an early stage. 3
Statistical analysis
Statistical analyses were performed using Graphpad Prism version 5.01 (Graphpad Software, 2007, La Jolla California, CA, USA). The correlation between HLA alleles (HLA-A, -B, -C, -DRB1 and –DQB1) and spontaneous regression or HPV-subtype were analyzed by contingency tables, using Fisher’s exact test to determine statistical significance (p ≤ 0.05). The Hardy-Weinberg equilibrium was not considered, as the focus of our study was not to calculate allele frequencies of the HLA alleles. We have assumed that the typed alleles are expressed on the host cell surfaces. Sample size calculation was not feasible, due to the lack of comparable biomarker performance values and limitation of the study population by the availability of material.
Nomenclature
The nomenclature for defining HLA alleles has been based on the IPD-HLA/IMGT allele database that has been established according the WHO nomenclature committee.
Results
Patient population
34 patients were included in the study. Two patients were excluded from the analysis, as all HLA typing reactions failed and no further DNA was available. Patient characteristics of the 32 remaining patients can be found in table 1. There was no missing data regarding the patient characteristics. Between patients with and without disease regression, there were no statistical differences mean age (30.6 vs 30.3 years, p=0.86), biopsy-LEEP interval (110 vs 114 days, p=0.29) and HPV16 positivity (5/14 (36%) vs 7/18 (39%), p=0.86).
HLA as a prognostic biomarker
Table 1. Patient characteristics
Age (mean, range in years)
Biopsy-LEEP interval (mean, range in days) HPV 16 positive (N, %)
Spontaneous disease regression overall (N, %)
HLA repertoire and spontaneous regression of high-grade CIN
30.5 (25-40) 112 (84-149) 12 (38%)
14 (44%)
Characteristic
Outcome N = 32
The results of the HLA-typing reactions can be found in table 2. In five patients, one or more HLA typing reactions failed; no further DNA was available for additional typing. No significant associations were found between the studied HLA genes and spontaneous regression of high- grade CIN in the entire study population, nor in the subgroups of HPV16 positive lesions and HPV16 negative lesions.
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