BackgroundHuman　papillomavirus　(HPV)　is　an　etiological　agent　of　cervical　cancer.　Yet　co-factors　are　believed　to　be　involved　in　HPV-mediated　carcinogenesis.　Polycyclic　aromatic　hydrocarbons　(PAHs)　are　considered　as　one　of　these　co-factors.　Epidemiologic　studies　have　associated　high　PAH　exposure　with　increased　risk　for　cancer　development.　To　date,　many　studies　focus　on　benzo[a]pyrene,　however,　the　role　of　other　PAHs　should　not　be　neglected.　This　study　aimed　to　compare　the　potential　of　different　PAHs　as　a　co-factor　in　HPV-mediated　carcinogenesis,　and　to　investigate　the　possible　mechanisms　involved.MethodsThe　effect　of　17　PAHs　on　high-risk　HPV　(HPV16)　were　examined　in　this　study.　HPV16　E7　oncogene　was　expressed　in　primary　cells　extracted　from　baby　rat　kidney　and　treated　with　PAHs.　The　co-transforming　ability　of　PAHs　were　measured　by　colony　formation　index　according　to　the　number　and　size　of　transformed　colonies.　Effects　of　PAHs　on　proliferation　of　HPV-null　(C33A)　and　-infected　(CaSki)　were　examined　using　CCK-8　assay.　Wound　healing　assay　and　matrigel　invasion　chambers　were　used　to　investigate　effects　of　PAHs　on　cell　motility　and　invasivion　of　HPV-null　(MCF7,　C33A)　and　-infected　(SiHa)　cells.ResultsBenzo[a]pyrene　(BaP),　dibenz[a,h]anthracene　(DBA)　and　indeno[1,2,3-cd]pyrene　(IDP)　showed　the　greatest　co-transforming　potential　in　the　baby　rat　kidney　cell　system.　Short-term　exposure　to　BaP,　DBA,　IDP　and　pyrene　(PR)　did　not　affect　proliferation　of　C33A　or　CaSki　cells,　however,　long-term　exposure　of　these　four　PAHs　led　to　dramatic　increase　in　growth　rate　of　CaSki　cells　by　120-140%.　Besides,　exposure　of　PAHs　has　an　effect　on　cell　motility　and　invasiveness　of　C33A　and　SiHa　cells,　but　not　for　MCF7　cells.　Exposure　of　BaP　and　DBA　enhanced　migration　(1.26　to　1.40-fold)　and　invasion　(1.68　to　1.94-fold)　capacity　of　C33A　cells.　Intriguingly,　exposure　of　all　four　types　of　PAHs　boosted　the　migration　(1.12　to　1.28-fold)　and　invasion　(1.26　to　1.40-fold)　capacity　of　SiHa　cells.ConclusionsOur　results　indicate　that　exposure　to　PAHs　can　be　a　key　co-factor　in　HPV-related　cancer　development.　They　could　act　on　all　three　stages,　namely　initiation,　promotion　and　progression.　Further　study　is　needed　to　unveil　the　mechanisms　by　which　PAHs　interact　with　HPV　to　cause　malignancy.