Prevalence of human papillomavirus and Helicobacter pylori in esophageal and gastroesophageal junction cancer biopsies from a case–control study in Ethiopia

Abstract

Background Ethiopia lies in the high-risk corridor of esophageal squamous cell carcinoma in East Africa, where individuals with this malignancy often do not report established risk factors, suggesting unidentified etiologies. Here, we report the prevalence of mucosal human papillomavirus (HPV) and of Helicobacter pylori ( H. pylori ) detection in endoscopy-obtained esophageal and gastroesophageal junction biopsies and in oral cell specimens taken at the time of esophageal cancer diagnosis in a case–control study in Addis Ababa, Ethiopia. Methods DNA extraction was performed from fresh frozen tissue and oral cell pellets obtained with saline solution gargling subsequently fixed with ethanol. Mucosal HPV and H. pylori DNA was detected using highly sensitive assays that combine multiplex polymerase chain reaction and bead-based Luminex technology. The proportions of specimens testing positive were expressed as percentages, with binomial 95% confidence intervals. Agreement of results between tissue biopsy and oral cell specimens was estimated using the kappa statistic. Comparison of study participants’ characteristics by test results was done using the Pearson chi-square test. Results HPV DNA was detected in 1 of 62 tumor specimens (2, 95% confidence interval (CI): 0–9%), corresponding to HPV16 type. HPV DNA was detected in the oral cavity of 7 cases (11, 95% CI: 5–22%) and 4 of 56 matched healthy controls (7, 95% CI: 2–17%), with multiple HPV types detected. Detection of H. pylori DNA was 55% (95% CI: 42–68%), and 20 of 34 H. pylori -positive specimens (59, 95% CI: 41–75%) were positive for the cagA gene. Agreement of detection rates between tissue and oral cells in cases was poor for HPV and for H. pylori . Conclusions The prevalence of mucosal-type HPV was very low, whereas H. pylori was more commonly detected, with a high proportion testing positive for the pro-inflammatory gene cagA . These novel findings remain to be replicated in larger studies and with the addition of serological determinations to better understand their biological significance in the context of esophageal and gastroesophageal junction cancers.

Risk factors for esophageal cancer in a high-incidence area of Malawi

“…HIV, CMV, HSV, and H. pylori infection are prevalent in Africa [12][13][14][15]. Our serological investigation revealed no association of EC presence with positive HIV serology, consistent with the nding of another study from Malawi [44], or with positive serology for CMV, EBV, HSV, or VZV.…”

“…HIV is known to be associated with the occurrence of lymphomas and cervical and anal carcinomas [12]. High prevalence rates in Africa have also been reported for cytomegalovirus (CMV), herpes simplex virus (HSV), and Helicobacter pylori infection [13][14][15]. Human papillomavirus (HPV) has been found in only a subset of patients (15% of those with ESCC) in Malawi [16].…”

Associations Between Gastric Cancer Risk and Virus Infection Other Than Epstein-Barr Virus: A Systematic Review and Meta-analysis Based on Epidemiological Studies

“…Fourteen studies investigated the prevalence of HPV including 901 patients with GC and 1,205 any controls ( 11 – 14 , 22 , 25 , 31 , 39 , 43 , 46 , 49 , 50 , 53 , 54 ). The pooled HPV prevalence in GC was 23.6% (95% CI 15.5%–31.6%, random model, heterogeneity P < 0.001).…”

“…Association between HPV infection and the risk of GC was observed (OR = 1.53, 95% CI 1.00–2.33, random model, heterogeneity P = 0.002) (see Figure 1c, Supplementary Digital Content 1, http://links.lww.com/CTG/A299 ). Five studies investigated the coinfection of H. pylori or EBV without extractable data for cases and controls ( 12 , 13 , 49 , 53 , 54 ). We reanalyzed after excluding controls with H. pylori -positive gastritis in the study by Bozdayi et al, and association still existed (OR = 1.63, 95% CI 1.05–2.54, random model, heterogeneity P = 0.002) (Figure 2 c) ( 53 ).…”

Association between infection with Campylobacter species, poor oral health and environmental risk factors on esophageal cancer: a hospital-based case–control study in Thailand

“…Numerous studies have found that cigarette smoking and alcohol consumption are significant risk factors for EC (50 times greater than that of individuals who neither drink nor smoke) [ 16 , 17 ]. Epidemiological evidence has shown that bacterial infections are associated with cancer and EC etiology [ 18 – 20 ]. Recently, researchers established that Campylobacter spp., characterized by oral upper digestive tract microbiota, is a major cause of foodborne bacterial infections in developed and developing countries worldwide [ 21 , 22 ].…”