Abstract
BackgroundPersistent 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.MethodsWe 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.ResultsEuropean (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).ConclusionOur results suggest that the association between HLA polymorphism and risk of ICC might be influenced by the distribution of HPV-16 variants.
Highlights
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
To investigate if the association pattern between human leukocyte antigen (HLA) class II genes and ICC is dependent on the distribution of HPV16 variants, we evaluated the HPV-16 variability in 107 patients enrolled in a case-control study [19], previously analyzed for HLA-DRB1, DQB1 and DQA1 polymorphisms
HPV-16 variants from E, AA, Af-1 and Af-2 branches were identified in 107 cases out of 112 HPV-16 positive ICC cases, because five samples were not included in variant analysis due to polymerase chain reaction (PCR) failure or disagreement between variant identity in E6 and L1 genes
Summary
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. Invasive cervical cancer (ICC) is one of the leading causes of cancer-related death in women in developing countries. The major risk factor is persistent infection with oncogenic types of human papillomavirus (HPV) with the contribution of additional co-factors such as smoking and oral contraceptive use. A strong association exists between persistent HPV infections and risk of squamous intraepithelial lesions (SIL), for HPV types 16 and 18 [2]. HPV DNA sequences are found in 2% to 44% of sexuallyactive asymptomatic women [3], but virtually all cervical carcinomas contain DNA of the high-risk types [4]. HPV infection is necessary but not sufficient to cause the development of ICC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
