Relationship between HPV and the biomarkers annexin A1 and p53 in oropharyngeal cancer.
BACKGROUND
Human papillomavirus (HPV) is often present in oropharyngeal cancers. Head and neck tumors have been examined for other molecular markers including p53 and annexin A1 (ANXA1). Here, we investigated the prevalence of HPV and its relationship with p53 and ANXA1 in patients with oropharyngeal cancer.


METHODS
We have analyzed tumor and adjacent mucosa from 22 patients with squamous cell carcinoma of the oropharynx in addition to samples of the oropharyngeal epithelium in subjects without cancer. We evaluated the presence of the HPV (subtypes 16/18 and 31/33) by chromogenic in situ hybridization. Additionally, we used immunofluorescence to examine the expression of p16, p53, ANXA1 and the phosphorylation of the ANXA1 residues Ser27 (ANXA1-SER) and Tyr21 (ANXA1-TYR).


RESULTS
We have detected the presence of HPV genome in 59% of the 22 tumors. Of those, 92% were also positive for p16 immunostaining. Furthermore, we demonstrated a reduction in the expression of p53 in HPV + compared to HPV- tumors. Also, a reduction was observed in the expression of ANXA1 in tumors compared to epithelium from the margins and from controls. We also noted a reduction in ANXA1-TYR in tumors. However, the expression of both ANXA1 and ANXA1-SER were elevated in the margins of the HPV + versus HPV- tumors.


CONCLUSIONS
Our results confirm a high prevalence of HPV in oropharyngeal cancer and a reduction in p53 expression in HPV + tumors. We observed a hypoexpression of ANXA1 and ANXA1-TYR in oropharyngeal cancer. The increase in ANXA1-SER in the margins of HPV + tumors suggests that the epithelium in these cases had been activated by an infectious agent. Those findings indicate that ANXA1 and its phosphorylated forms can play important roles in the response to HPV infection and the carcinogenesis of the oropharynx.
Post-Graduation in Health Science, Faculty of Medicine (FM), Federal University of Mato Grosso (UFMT), Mato Grosso, MT 78060-900, Brazil ; Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK ; Henry Wellcome Laboratory, University of Liverpool, 1st Floor, Nuffield Building, Liverpool L69 3GE, UK.
Cleberson Jean Dos Santos
CJ
Queiroz
Post-Graduation in Health Science, Faculty of Medicine (FM), Federal University of Mato Grosso (UFMT), Mato Grosso, MT 78060-900, Brazil.
Cíntia Mara de Amorim Gomes
CM
Nakata
William Harvey Research Institute; Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
Egle
E
Solito
Post-Graduation in Health Science, Faculty of Medicine (FM), Federal University of Mato Grosso (UFMT), Mato Grosso, MT 78060-900, Brazil ; Department of Basic Science in Health; Faculty of Medicine (FM), Federal University of Mato Grosso (UFMT), Mato Grosso, MT 78060-900, Brazil.
Amílcar Sabino
AS
Damazo
Annexin A1; Cancer; HPV; Oropharynx; p53