The Significance of Human Papillomavirus Receptors Related Genetic Variants in Cervical Cancer Screening

ABSTRACT To investigate the relationship between single nucleotide polymorphisms (SNPs) in human papillomavirus (HPV) receptor associated genes and HPV susceptibility and clinical outcomes in Chinese women, from October 2016 to March 2020, a total of 3,066 women were recruited for a 3-year prospective population-based cervical cancer screening clinical trial. The primary endpoint was histological cervical intraepithelial neoplasia 2 and worse (CIN2+). Twenty-nine SNPs of HPV receptor associated genes on women with available cytology residual samples at baseline were detected using MALDI-TOF MS. Eligible data were available for 2,938 women. Rs16894821 (GG versus AA, OR =1.71 [1.08 to 2.69]) and rs724236 (TT versus AA, OR = 1.73 [1.14 to 2.62]) in SDC2 were significantly related to the HPV susceptibility. And rs2575712 (TT versus GG, OR = 2.78 [1.22 to 6.36]) in SDC2 was associated with increased HPV 16/18 susceptibility. Four SNPs (rs1047057 and rs10510097 in FGFR2 gene, rs2575735 in SDC2 gene, and rs878949 in HSPG2 gene) were significantly associated with persistent HPV infection. Importantly, the genotypes of rs16894821 under recessive model (GG versus AA/AG, OR = 2.40 [1.12 to 5.15]) in SDC2 and rs11199993 under dominant model (GC/CC versus GG, OR = 1.64 [1.01 to 2.68]) in FGFR2 were significantly associated with the disease progression. Finally, SNPs showed comparable efficacy in detecting CIN2+ for the women infected with non-HPV16/18 compared with cervical cytology (sensitivity: 0.51 [0.36 to 0.66] versus 0.44 [0.30 to 0.60], specificity: 0.96 [0.96 to 0.97] versus 0.98 [0.97 to 0.99], positive predictive value: 0.23 [0.15 to 0.33] versus 0.33 [0.22 to 0.47], and negative predictive value: 0.99 [0.98 to 0.99] versus 0.99 [0.98 to 0.99]). SNPs in HPV receptor related genes may influence HPV susceptibilities and clinical outcomes in Chinese women. IMPORTANCE Virus receptors are known to mediate virus attachment and further lead to virus infection of the host cells. In the current study, we investigated the relationship between single nucleotide polymorphisms (SNPs) in human papillomavirus (HPV) receptor associated genes and HPV susceptibility and clinical outcomes in Chinese women, and to explore the new triaging strategy for non-16/18 high-risk HPV infection.