Frequency distribution of HLA alleles and haplotypes in Uyghur women with advanced squamous cell cervical cancer and relation to HPV status and clinical outcome.

Abstract

This study aims to investigate the association of human leukocyte antigen (HLA) alleles and haplotypes in Uyghur women with advanced squamous cell cervical cancer (SCC). A total of 131 Uyghur patients with advanced SCC (IIb-IVa) and 91 healthy subjects from Xinjiang province were genotyped for HLA-I and II genes using Polymerase Chain Reaction Sequence Based Typing. The different frequencies of HLA alleles and haplotypes between patients and controls were compared and the correlations were analyzed between HLA distribution and HPV status and prognosis. (1) The frequencies of B*51:01, DRB1*07:01, DQB1*02:01, A*01:01-C*06:02, A*01:01-DRB1*07:01, C*06:02-DQB1*02:01, DRB1*07:01-DQB1*02:01 and C*06:02-DRB1*07:01-DQB1*02:01 in cancer group were higher than control group whereas the frequencies of B*44:02, B*58:01, C*05:01, DRB1*04:01, DRB1*12:01, DRB1*13:01, DQB1*02:02, DQB1*05:02, DRB1*03:01-DQB1*02:02 and DRB1*04:01-DQB1*03:02 in cancer group were lower than control group (P<0.05). (2) The frequencies of A*01:01-C*06:02, A*01:01-DRB1*07:01, C*06:02-DQB1*02:01, DRB1*07:01-DQB1*02:01 and C*06:02-DRB1*07:01-DQB1*02:01 in HPV positive group were lower than HPV negative group, differences of which were statistically significant (P<0.05). (3) B*44:02 and B*58:01 were associated with reduced disease-specific survival (DSS) (P=0.010 and 0.007). (4) Multivariate Cox proportional hazard models revealed that age, International Federation of Gynaecology and Obstetrics (FIGO) stage, tumor differentiation and allele B*58:01 as independent predictors for DSS while FIGO stage and tumor differentiation as independent factors for DFS. In the development and progression of advanced SCC among Uyghur population, the HLA alleles and its haplotypes play an important role. B*58:01 allele may act asan independent predictor for DSS.