Variants in human papillomavirus receptor and associated genes are associated with type-specific HPV infection and lesion progression of the cervix

Oncotarget. 2016 Jun 28;7(26):40135-40147. doi: 10.18632/oncotarget.9510.

Abstract

Human papillomavirus (HPV) infects cervical epithelial cells through cellular membrane receptors, and then induces the initiation and progression of cervical cancer. Single nucleotide polymorphisms (SNPs) may impact the susceptibility and outcome of diseases, but it's still unknown whether variant in HPV receptor and associated genes is associated with type-specific HPV infection and cervical lesion progression. We examined 96 SNPs in 8 genes which may participate in the HPV infection process in 875 samples with HPV negative or single HPV16, 18, 52, 58 positive from 3299 cervical exfoliated cell samples, by Illumina BeadXpress VeraCode platform, and analyzed the correlation between the SNPs and type-specific HPV infection and cervical lesions progression. We found rs28384376 in EGFR and rs12034979 in HSPG2 significantly correlated to HPV16 infection; rs2575738, rs2575712, rs2575735 in SDC2 and rs6697265 in HSPG2 significantly correlated to HPV18 infection; rs10510097 in FGFR2, rs12718946 in EGFR significantly correlated to HPV52 infection; rs4947972 in EGFR, rs2981451 in FGFR2, rs2575735 in SDC2 significantly correlated to HPV58 infection. And rs3135772, rs1047057 and rs2556537 in FGFR2, rs12034979 in HSPG2, rs16894821 in SDC2 significantly correlated to cervical lesion progression induced by HPV16 infection; rs6697265 and rs6680566 in HSPG2, rs16860426 in ITGA6 by HPV18 infection; rs878949 in HSPG2, rs12718946 and rs12668175 in EGFR by HPV52 infection; no SNP by HPV58 infection. Our findings suggest that HPV receptor and associated gene variants may influence the susceptibilities to HPV type-specific infection and cervical lesion progression, which might have a potential application value in cervical cancer screening and therapy.

Keywords: HPV receptor; SNP; cervical lesions; type-specific HPV infection.

MeSH terms

  • Adult
  • Aged
  • Cervix Uteri / pathology
  • DNA, Viral / genetics
  • Disease Progression
  • Early Detection of Cancer
  • ErbB Receptors / genetics
  • Female
  • Genetic Variation
  • Genotype
  • Haplotypes
  • Heparan Sulfate Proteoglycans / genetics
  • Humans
  • Middle Aged
  • Papillomaviridae / genetics*
  • Papillomavirus Infections / virology*
  • Polymorphism, Single Nucleotide
  • Receptors, Virus / metabolism*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology*
  • Young Adult

Substances

  • DNA, Viral
  • Heparan Sulfate Proteoglycans
  • Receptors, Virus
  • perlecan
  • EGFR protein, human
  • ErbB Receptors