IMR Press / FBE / Volume 8 / Issue 1 / DOI: 10.2741/E747

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


TLR4 down-regulation identifies high risk HPV integration in head and neck squamous cell carcinomas

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1 Department of Clinical and Experimental Medicine, Section of Pathological Anatomy, University of Foggia, Foggia, Italy
2 Laboratory of Preclinical and Translational Research, IRCCS-CROB, Oncological Reference Centre of Basilicata, Rionero in Vulture (PZ), Italy
3 Section of Pathological Anatomy, Polytechnic University of Marche, Ancona, Italy
4 Section of Pathological Anatomy, National Cancer Institute IRCCS ‘G. Pascale’ Foundation, Napoli, Italy
5 Department of Laboratory and Services, Section of Histopathology, Research and Care Foundation ‘Giovanni Paolo II’, Catholic University of Sacred Heart (UCSC), Campobasso, Italy
6 Department of Surgical, Oncological and Stomatological Disciplines (Di.Chir.On.S.), University of Palermo, Via del Vespro 129, 90127 Palermo, Italy
7 Department 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
8 Department of Neurosciences and Reproductive and Odontostomatological Sciences, University of Napoli ‘Federico II’, Napoli, Italy
9 Department of Advanced Biochemical Sciences, Section of Anatomic Pathology, University of Napoli Federico II, Via S Pansini 5, Napoli, Italy
10 Department of Experimental and Clinical Medicine, Dental Clinic, University of Foggia, Foggia, Italy
11 Section of Clinic Pathology, OO.RR., Foggia, Italy
12 Department of Head and Neck Surgery, Second University of Naples, Naples, Italy
13 Department Medical-Surgical Specialties, Section of Oral Medicine, Policlinico, University of Catania, Catania, Italy

*Author to whom correspondence should be addressed.


Front. Biosci. (Elite Ed) 2016, 8(1), 15–28;
Published: 1 January 2016

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. 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 = 0.002). There is no statistical correlation between TLR4 intensity and PCR HPV results (p > 0.0.5). Point-biserial correlation coefficient revealed significant association between TLR4 expression and HR-HPV integration status (p = 0.0001) and between TLR4 expression index and HR-HPV infection (p = 0.001). These data show that TLR4 down-regulation is strongly associated to both HPV-16 infection and its integration into the host DNA.

Squamous Cell Carcinomas
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