Abstract
BackgroundHuman 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.MethodsWe 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).ResultsWe 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.ConclusionsOur 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.
Highlights
Human papillomavirus (HPV) is often present in oropharyngeal cancers
We have noticed a reduced expression of annexin A1 (ANXA1) in oropharyngeal cancer compared to the expression observed in the epithelium of the tumor margin and in the non-neoplastic controls, a finding that is in agreement with the majority of studies focusing on cancers of the head and neck
Our findings confirm the presence of the HPV genome in a substantial proportion of oropharyngeal tumors, as well as a reduction in the expression of p53 in HPV + tumors
Summary
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). Cancers of the head and neck are a global health problem These tumors occur frequently, especially among low-income populations, with a high social cost because of the associated morbi-mortality. This pathology affects approximately 633,000 people worldwide causing 325,000 deaths [1]. A group of patients exists that lack these precursors, leading to the suspicion that other factors might play important roles in the Cancer of the oropharynx stands out from other topographies in the head and neck region due to its strong association with the infection caused by human papillomavirus (HPV). Various studies have demonstrated the presence of high-risk carcinogenic subtypes (especially subtypes 16, 18, 31 and 33) in a substantial proportion of these tumors [6]. Recent studies have shown high infection rates through the demonstration of the presence of viral genome [5,7,8] or using immunostaining directed to p16, a protein known to be upregulated in the presence of high-risk HPVs and frequently used as a surrogate of HPV infection [7,9,10]
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