Interaction between polymorphisms of the human leukocyte antigen and HPV-16 variants on the risk of invasive cervical cancer.
BACKGROUND
Persistent infection with oncogenic types of human papillomavirus (HPV) is the major risk factor for invasive cervical cancer (ICC), and non-European variants of HPV-16 are associated with an increased risk of persistence and ICC. HLA class II polymorphisms are also associated with genetic susceptibility to ICC. Our aim is to verify if these associations are influenced by HPV-16 variability.


METHODS
We characterized HPV-16 variants by PCR in 107 ICC cases, which were typed for HLA-DQA1, DRB1 and DQB1 genes and compared to 257 controls. We measured the magnitude of associations by logistic regression analysis.


RESULTS
European (E), Asian-American (AA) and African (Af) variants were identified. Here we show that inverse association between DQB1*05 (adjusted odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.39-1.12]) and HPV-16 positive ICC in our previous report was mostly attributable to AA variant carriers (OR = 0.27; 95%CI: 0.10-0.75). We observed similar proportions of HLA DRB1*1302 carriers in E-P positive cases and controls, but interestingly, this allele was not found in AA cases (p = 0.03, Fisher exact test). A positive association with DRB1*15 was observed in both groups of women harboring either E (OR = 2.99; 95% CI: 1.13-7.86) or AA variants (OR = 2.34; 95% CI: 1.00-5.46). There was an inverse association between DRB1*04 and ICC among women with HPV-16 carrying the 350T [83L] single nucleotide polymorphism in the E6 gene (OR = 0.27; 95% CI: 0.08-0.96). An inverse association between DQB1*05 and cases carrying 350G (83V) variants was also found (OR = 0.37; 95% CI: 0.15-0.89).


CONCLUSIONS
Our results suggest that the association between HLA polymorphism and risk of ICC might be influenced by the distribution of HPV-16 variants.
de Araujo Souza
Patricia S
PS
Ludwig Institute for Cancer Research, São Paulo, Brazil.
Maciag
Paulo C
PC
Ribeiro
Karina B
KB
Petzl-Erler
Maria Luiza
ML
Franco
Eduardo L
EL
Villa
Luisa L
LL
D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II