The significance of human papillomavirus receptors related genes variants in cervical cancer screening: a longitudinal study of Chinese population

Objective To investigate the relationship between single nucleotide polymorphisms (SNPs) in human papillomavirus (HPV) receptor gene and HPV susceptibility and the outcomes in Chinese women. Study design A cohort study. Setting Lishui, Zhejiang, China. Population 3066 women were recruited. Methods 29 SNP sites of HPV receptor gene on women with available cytology residual samples were detected. Main outcome measures Develop to cervical intraepithelial neoplasia 2 and worse (CIN2+). Results: 2938 women with sufficient cytology samples performed SNP sites detection. Rs16894821 [GG vs. AA: OR =1.71 (1.08-2.69)] and rs724236 [TT vs. AA: OR=1.73 (1.14-2.62)] in SDC2 increased the HPV susceptibility. TT genotype of rs2575712 in SDC2 was associated with an increased HPV 16/18 susceptibility [OR=2.78 (1.22-6.36)]. Four SNPs (rs1047057 and rs10510097, rs2575735, and rs878949) were significantly associated with HPV persistent infection. In addition, the frequencies of genotype of rs16894821 under recessive model [OR=2.40 (1.12-5.15)] in SDC2, and rs11199993 under dominant model [OR=1.64 (1.01-2.68)] in FGFR2 were significantly associated with the disease progression. Importantly, we found that HPV test in combination with SNPs with sensitivity of 0.51 (0.36-0.66) and specificity of 0.96 (0.96-0.97) in predicting CIN2+ on women with non-HPV16/18+, which had similar performance to HPV test combined with cytology test with sensitivity of 0.44 (0.30-0.60) and specificity of 0.98 (0.97-0.99). Conclusion: Gene variants in HPV receptor related gene may influence the HPV susceptibilities and the outcome of HPV infection. HPV combined with SNPs is a promising alternative to HPV test combined with cytology test in patients with non-HPV16/18 infection.