Detection of Human Papillomavirus DNA and p53 Gene Mutations in Esophageal Cancer Samples and Adjacent Normal Mucosa

Abstract

Background/Aim: There is evidence of a possible etiological role of human papillomaviruses (HPVs) in the development of esophageal tumors. Loss of function of the wild-type p53 tumor suppressor gene product by binding to E6 oncoproteins of high-risk HPVs is considered an important event in tumor development. The aim of this study was to verify the prevalence of HPV infection and p53 mutation in esophageal tumor tissue samples and in the adjacent normal mucosa in patients from a high-risk area in Italy. Methods: DNA from 33 biopsy specimens (17 tumor sample biopsies and 16 samples of adjacent normal mucosa) was screened for HPV DNA using two polymerase chain reaction based procedures. Restriction fragment length polymorphism analysis was used for typing. Screening of p53 mutations was performed with polymerase chain reaction-single strand conformation polymorphism analysis and DNA sequencing. Results: Overall, 8 of 17 patients presented HPV DNA; HPV 16 was detected in 4 of 8 samples. Samples from tumors and adjacent mucosa were positive for mucosal HPVs in 7 of 17 and 4 of 16 cases, respectively. In 1 case, HPV DNA was detected in the normal mucosa only. None of the samples contained HPVs of the epidermodysplasia verruciformis or cutaneous groups. Mutations of p53 were detected in two HPV DNA negative samples. In both cases, the mutation was present in the tumor only. Conclusions: Our results are in favor of the involvement of both aberrant p53 expression and HPV infection in the development of esophageal tumors. The high HPV infection rate in patients from a high-risk region suggests that subjects harboring HPVs (in particular HPV 16) in the esophagus should be considered at risk of esophageal malignancies.

The relationship between p16 expression and high-risk human papillomavirus infection in squamous cell carcinomas from sites other than uterine cervix: a study of 137 cases

“…This finding is similar to several large series in the literature, where the reported rate of HPV positivity in oropharyngeal SCCs ranged from 47% to 72% [1,2,[4][5][6]. In line with these studies, we found that p16 is highly sensitive and specific for HR-HPV in the oropharynx, especially the tonsil [20,21,27]. These findings would seem to obviate the need for direct HPV testing, at least in the tonsil.…”

“…Although SCCs of the oropharynx are most strongly associated with HR-HPV infection, head and neck SCCs (HNSCCs) of other sites including SCCs of the sinonasal cavity, nasopharynx, oral cavity, and larynx have also been shown to harbor the virus, and HR-HPV has been demonstrated in several non-head and neck sites including lung and esophagus [8][9][10][11][12][13][14][15][16][17][18][19][20][21].…”

HPV infections and oesophageal cancer

“…126 In our series of 700 SCCs from China, of which 117 (16.9%) were HPV DNA positive, 11 HPV signals were detected in the surrounding hyperplastic and dysplastic epithelia in 5.6% of patients, and in the resection margins of 0.2% cases, figures that agree with another recent report. 118 The presence of HPV in the adjacent normal and dysplastic epithelium fits in with the "condemned mucosa" concept, recently proposed to explain the pathogenesis of multifocal HPV induced carcinogenesis in the genital tract and in the upper aerodigestive tract, 127 including oesophageal SCC. 10 124 …”

Human papillomavirus in high- and low-risk areas of oesophageal squamous cell carcinoma in China

“…Accumulating evidence on the presence of HPV DNA in normal oesophageal epithelium (Chang et al, 2000;Zhou et al, 2003) and in cancer precursor lesions (Pillai and Nair, 2000;Astori et al, 2001) suggests an involvement of HPV in very early stages of the classical dysplasia -carcinoma sequence. The notion was also supported by the demonstration of HPV infection using serologic assays with enzyme-linked immunosorbent assays (ELISAs) (Han et al, 1996).…”