Detection of human papillomavirus in esophageal and gastroesophageal junction tumors: A retrospective study by real-time polymerase chain reaction in an instutional experience from Turkey and review of literature

Abstract

Esophageal cancer is a poor-prognosis malignancy that ranks eighth among all cancer types, and its prevalence shows differences among geographical regions. Although the most important risk factors for esophageal carcinoma are alcohol and smoking, viral infections, particularly HPV infection, are also considered among etiological agents. Our study aims to detect the presence of HPV in esophageal cancers in our patient population and to investigate its correlation with clinico-pathological parameters.

We investigated the presence of HPV-DNA by real-time polymerase chain reaction in a total of 52 patients with esophageal cancer. Subtype analysis was performed in positive cases and was correlated with selected clinico-pathological parameters.

Five (9.6%) of 52 tumor samples, 3 squamous cell carcinomas (3/33 cases) and 2 adenocarcinomas (2/19 cases), were HPV-DNA-positive. Subtype analysis could be performed in four HPV-DNA-positive cases, of which three were HPV type-39 and 1 was type-16. The Marmara region, where the present study was carried out, is a region with low-moderate risk for esophageal cancer, and the prevalence of HPV-DNA in these tumors is similar to the prevalence of HPV-DNA reported in the literature for regions with similar risk.

In conclusion, we detected HPV DNA in a subset of esophageal and gastroesophageal junction tumors. HPV infection may have a role in esophageal carcinogenesis and high-risk HPV subtypes can particularly be considered among risk factors since the prevalence of high risk HPV infection has also been found to be increased in regions with a high risk for esophageal cancer compared to low-moderate risk regions.

Introduction

Esophageal cancer is a rapidly progressive and poor-prognosis disease with late manifestation [1]. It ranks eighth among all types of cancer with a prevalence rate of 4.2% [2], [4]. The most common tumor type of esophageal cancer is squamous cell carcinoma (SCC) followed by adenocarcinoma [2], [5], [6]. These two tumor types account for the great majority of esophageal cancers, and there are significant epidemiological/etiological differences between them [2], [3], [7]. Whilst SCCs are more prevalent in the eastern countries and developing countries, the incidence of adenocarcinomas, which were less prevalent in the recent years, increases by 5–10% each year particularly in the industrialized western countries [3]. This tumor, which appears at the age of 65 years in average, shows male predominance particularly for adenocarcinomas. Its incidence shows variation among countries, as well as among geographical regions in the same country. Countries where the disease is more prevalent include China, Japan, Korea, India, Singapore, South Africa, Russia, Turkmenistan and Iran. Esophageal cancer, which has low-moderate risk in Turkey, is more prevalent especially in the Eastern Anatolian Region [3], [7], [8]. The etiology of esophageal carcinomas includes tobacco and alcohol consumption, local environmental and nutritional carcinogens, vitamin and mineral deficiencies, achalasia, tylosis, caustic stenosis, celiac disease, Plummer–Vinson syndrome, gastro-esophageal reflux (GER), Barrett's esophagus (BE) and Human Papillomavirus (HPV) [5], [8].

HPV is worldwide one of the most common sexually-transmitted agents in both females and males. The exact incidence and prevalence are not known since it is not a disease of mandatory reporting. It is agreed that HPV infection is an effective factor in the carcinogenesis of cervix uteri, skin, oral cavity, pharynx, larynx, and anogenital system tumor [6], [9], [10]. Although the relation between HPV infection and esophageal cancer has been identified in many regions of the world, the role of HPV infection in the etiology of esophageal cancer is not clear in Turkey, particularly in our region.

The present study aimed to detect the prevalence of HPV-DNA in the esophageal cancers in our region, to determine which types are more prevalent in the patients from whom HPV-DNA was isolated, and to evaluate the relation with clinico-pathological data.