Relationships of early esophageal cancer with human papillomavirus and alcohol metabolism

Abstract

Background: It is well known that an alcohol consumption habit together with inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) is an important risk factor for the development of esophageal squamous cell carcinoma (ESCC). It remains controversial whether human papillomavirus (HPV) infection contributes to the occurrence/development of ESCC. There has been no study in which the relationship between ESCC and HPV in addition to alcohol dehydrogenase-1B (ADH1B) and ALDH2 genotypes was evaluated.

Aim: To evaluate relationships between HPV infection and development of esophageal cancer, particularly early esophageal cancer, based on ADH1B/ALDH2 polymorphisms.

Methods: We conducted an exploratory retrospective study using new specimens, and we enrolled 145 patients who underwent endoscopic resection for superficial ESCC and had been observed for more than two years by both physical examination and endoscopic examination in Hokkaido University Hospital. Saliva was collected to analyze genetic polymorphisms of ADH1B/ALDH2. We performed in situ hybridization for resected specimens to detect HPV by using an HPV type 16/18 probe.

Results: HPV was detected in 15 (10.3%) of the 145 patients with ESCC. HPV-positive rates in inactive ALDH2*1/*2 and ALDH2*1/*1 + *2/*2 were 10.8% and 9.8%, respectively (P = 1.00). HPV-positive rates in slow-metabolizing ADH1B*1/*1 and ADH1B*1/*2 + *2/*2 were 12.0% and 10.0%, respectively (P = 0.72). HPV-positive rates in the heavy or moderate alcohol consumption group and the light or rare consumption group were 11.1% and 8.7%, respectively (P = 0.68). HPV-positive rates in the heavy smoking group and the light or no smoking group were 11.8% and 8.3%, respectively (P = 0.59). The 3-year incidence rates of secondary ESCC or head and neck cancer after initial treatment in the HPV-positive and HPV-negative groups were 14.4% and 21.4% (P = 0.22), respectively.

Conclusion: In the present situation, HPV status is considered to be less important than other risk factors, such as alcohol consumption, smoking habit, ADH1B/ALDH2 polymorphisms, and HPV status would therefore have no effect on ESCC risk management.

Keywords: Alcohol dehydrogenase-1B; Aldehyde dehydrogenase-2; Early esophageal cancer; Endoscopic resection; Esophageal squamous cell carcinoma; Human papillomavirus.

Figure 1

Metachronous development of esophageal squamous cell carcinoma or head and neck squamous cell carcinoma after endoscopic mucosal dissection/endoscopic mucosal resection. The median follow-up period was 73 mo (range, 24-244 mo). The 3-year incidence rates of secondary esophageal squamous cell carcinoma or head and neck squamous cell carcinoma after initial treatment in the human papillomavirus (HPV)-positive and HPV-negative groups were 14.4% and 21.4% (P = 0.22), respectively. SCC: Squamous cell carcinoma; HPV: Human papillomavirus.