Genetic Susceptibility to Cervical Neoplasia

Twin and family studies suggest that genetic factors play a role in cervical neoplasia susceptibility. Both rare high penetrant and common low penetrant host genetic variants have been shown to influence the risk of HPV persistence, and common variants have been shown to influence the risk of cervical neoplasia. The strongest associations with cervical neoplasia are with HLA genes, with associations having been demonstrated to both reduce and increase the risk of the disease. Fine-mapping using imputed amino-acid sequences of HLA-types has shown that the HLA associations are driven primarily by the HLA-B amino acid position 156 (B156), and HLA-DRB1 amino acid positions 13 and 71. This is informative about the types of peptides that may be useful for peptide vaccines. As cervical neoplasia is at least moderately heritable, genetics may be able to identify those at high or low disease risk. Using the findings of hundreds of disease-associated SNPs to calculate genetic risk scores, it has been shown that women with genetic risk scores in the bottom 10% of the population have very low risk of cervical neoplasia (<0.17%), whereas those in the top 5% have 22% risk of developing the disease. Further large scale genetic studies would be helpful to better define particularly the non-MHC component of genetic risk.