Association of the Vaginal Microbiota with Human Papillomavirus Infection in a Korean Twin Cohort.docVIP

AssociationoftheVaginalMicrobiotawithHuman PapillomavirusInfectioninaKoreanTwinCohort JungEunLee1,SungheeLee1,HeetaeLee1,Yun-MiSong2,KayoungLee3,MinJiHan4,JoohonSung4, GwangPyoKo1* 1Department of Environmental Health and Institute of Health and Environment, School of Public Health, Seoul National University, Seoul, Republic of Korea, 2DepartmentofFamilyMedicine,SamsungMedicalCenter,SungkyunkwanUniversitySchoolofMedicine,Seoul,RepublicofKorea,3DepartmentofFamilyMedicine, Busan Paik Hospital, Inje UniversityCollege ofMedicine, Busan,Republic ofKorea, 4Department ofEpidemiology,School ofPublicHealth, SeoulNational University, Seoul,RepublicofKorea Abstract Human papillomavirus (HPV) is the most important causative agent of cervical cancers worldwide. However, our understandingofhowthevaginalmicrobiotamightbeassociatedwithHPVinfectionislimited.Inaddition,theinfluenceof humangeneticandphysiologicalfactorsonthevaginalmicrobiotaisunclear.Studiesontwinsandtheirfamiliesprovide the ideal settings to investigate the complicated nature of human microbiota. This study investigated the vaginal microbiotaof68HPV-infectedoruninfectedfemaletwinsandtheirfamiliesusing454-pyrosequencinganalysistargeting thevariableregion(V2–V3)ofthebacterial16SrRNAgene.Analysisofthevaginalmicrobiotafrombothpremenopausal women and HPV-discordant twins indicated that HPV-positive women had significantly higher microbial diversity with a lowerproportionofLactobacillusspp.thanHPV-negativewomen.Fusobacteria,includingSneathiaspp.,wereidentifiedasa possiblemicrobiologicalmarkerassociatedwithHPVinfection.Thevaginalmicrobiotasoftwinpairsweresignificantlymore similartoeachotherthantothosefromunrelatedindividuals.Inaddition,thereweremarkedsignificantdifferencesfrom thoseoftheirmother,possiblyduetodifferencesinmenopausalstatus.Postmenopausalwomenhadalowerproportionof Lactobacillusspp.andasignificantlyhighermicrobiotadiversity.ThisstudyindicatedthatHPVinfectionwasassociatedwith thecompositionofthevaginalmicrobio