title: TLR4 down-regulation identifies high risk HPV infection and integration in head and neck squamous cell carcinomas.
abstract: TLRs are main actors of the innate immune response against HPV. There are very few studies on the role of TLRs mediated HPV clearance in Head and Neck oncology. Our aim was to evaluate whether TLR4 expression identifies HPV infection and/or HR-HPV integration status in oral and oropharyngeal cancers. By immunohistochemistry we assessed TLR4 levels in OSCC/OPSCC. To detect viral integration or episomic status In situ hybridization for HPV-DNA and Pyro-sequencing techniques have been performed. The relationship between TLR4 expression with HPV infection status has been investigated. ISH HPV positive samples have reported lower levels of TLR4 intensity than negative samples (p = .002). There was no statistical correlation between TLR4 intensity and PCR HPV results (p more than 0.0.5). Point-biserial correlation coefficient revealed significant association between TLR4 expression and HR-HPV integration status (p = .0001) and between TLR4 expression index and HR-HPV infection (p = .001). These data have shown that TLR4 down-regulation is strongly associated to both HPV-16 infection and its integration into the host DNA.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pathological Anatomy, University of Foggia, Foggia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pannone
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pathological Anatomy, University of Foggia, Foggia, Italy.
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Bufo
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pathological Anatomy, University of Foggia, Foggia, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Pace
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-CROB, Oncological Reference Centre of Basilicata, Rionero in Vulture (PZ), Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lepore
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Pathological Anatomy, University of Foggia, Foggia, Italy.
authors.forename: Giuseppe M
authors.initials: GM
authors.lastname: Russo
authors.affiliation: Section of Pathological Anatomy, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Rubini
authors.affiliation: Section of Pathological Anatomy, National Cancer Institute IRCCS 'G. Pascale' Foundation, Napoli, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.affiliation: Section of Pathological Anatomy, National Cancer Institute IRCCS 'G. Pascale' Foundation, Napoli, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Aquino
authors.affiliation: Department of Laboratory and Services, Section of Histopathology, Research and Care Foundation Giovanni Paolo II, Catholic University of Sacred Heart (UCSC), Campobasso, Italy, angelasantoro1@hotmail.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Santoro
authors.affiliation: Department of Surgical, Oncological and Stomatological Disciplines (Di.Chir.On.S.), University of Palermo, Via del Vespro 129, 90127 Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Campisi
authors.affiliation: epartment of Sciences for the Promotion of the Maternal and Childhood Health G. D'Alessandro, Section of Anatomic Pathology, University of Palermo, A.O.U. Policlinico P. Giaccone, Palermo, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Rodolico
authors.affiliation: epartment of Neurosciences and Reproductive and Odontostomatological Sciences, University of Napoli Federico II, Napoli, Italy.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bucci
authors.affiliation: Department of Advanced Biomedical Sciences, Pathology Section, University of Naples "Federico II", Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ilardi
authors.affiliation: Department of Advanced Biochemical Sciences, Section of Anatomic Pathology, University of Napoli Federico II, Via S Pansini 5, Napoli, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mascolo
authors.affiliation: Department of Advanced Biomedical Sciences, Pathology Section, University of Naples "Federico II", Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Merolla
authors.affiliation: Department of Experimental and Clinical Medicine, Dental Clinic, University of Foggia, Foggia, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Lo Muzio
authors.affiliation: Section of Clinic Pathology, OO.RR., Foggia, Italy, 12Department of Head and Neck Surgery, Second University of Naples, Naples, Italy.
authors.forename: Iole
authors.initials: I
authors.lastname: Natalicchio
authors.affiliation: Department of Head and Neck Surgery, Second University of Naples, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Colella
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-CROB, Oncological Reference Centre of Basilicata, Rionero in Vulture (PZ), Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Laurenzana
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-CROB, Oncological Reference Centre of Basilicata, Rionero in Vulture (PZ), Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Trino
authors.affiliation: Department Medical-Surgical Specialties, Section of Oral Medicine, Policlinico, University of Catania, Catania, Italy.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Leonardi
authors.affiliation: Department of Neurosciences and Reproductive and Odontostomatological Sciences, University of Napoli Federico II, Napoli, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bucci
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000235:genetics / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D004279:DNA, Viral / Q000302:isolation & purification; D015536:Down-Regulation; D005260:Female; D006258:Head and Neck Neoplasms / Q000821:virology*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D016662:Virus Integration
chemical_list: D004279:DNA, Viral; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4