Is esophageal cancer caused by Human Papillomavirus (HPV)?

Is HPV a Cause of Esophageal Cancer?

Based on the most recent and highest quality evidence, HPV is not considered a major causative factor for esophageal cancer, particularly esophageal squamous cell carcinoma (OSCC). 1

Evidence Regarding HPV and Esophageal Cancer

• The Cancer Genome Atlas (TCGA) demonstrated that esophageal squamous cell carcinoma has a molecular profile consistent with HPV-negative squamous cell carcinoma, suggesting that any association between HPV and OSCC likely reflects regional variations in HPV prevalence rather than a true causative relationship 1

• While HPV infection has been suggested as potentially associated with OSCC in some studies, comprehensive genomic analysis does not support a significant causative role in esophageal carcinogenesis 1

• The primary established risk factors for esophageal squamous cell carcinoma include:

  • Tobacco use and alcohol consumption (particularly in non-endemic areas) 1
  • Recurrent chemical or physical insult to the esophageal mucosa 1
  • Low intake of fruits and vegetables 1
  • Thermal injury from hot beverages in certain regions 1

Geographic Variations in HPV Association

• Studies examining the relationship between HPV and esophageal cancer show significant geographic variation in results:

  • In high-risk regions for OSCC, research has found inconsistent evidence regarding HPV's role 2
  • A cross-sectional study in Linxian, China (a high-risk area) found that HPV infection rates were similar between individuals with no dysplasia (13%) and those with various grades of dysplasia, suggesting HPV is not a major risk factor for OSCC progression in this population 2

• Meta-analysis data has shown that while HPV-16 can be detected in some ESCC cases (11.67%), and may be associated with increased risk (OR=3.55), the evidence is insufficient to conclude that HPV plays a definitive causative role in esophageal carcinogenesis 3

Contrasting Evidence

• Some regional studies have reported higher HPV detection rates in esophageal tumor tissues compared to normal controls, particularly in high-incidence regions like Shantou, China 4

• There has been a reported increase in esophageal papilloma incidence, with approximately half of tested patients showing high-risk HPV in one study, raising theoretical concerns about future esophageal cancer risk 5

• However, other studies found no HPV DNA in esophageal cancer specimens from Korean patients, further highlighting geographic variations 6

Clinical Implications

• Unlike oropharyngeal cancers, where HPV is a well-established causative agent (particularly HPV types 16,18,31, and 33), the evidence does not support routine HPV testing or HPV-targeted prevention strategies specifically for esophageal cancer 1

• The primary focus for esophageal cancer prevention should remain on established risk factors, particularly tobacco and alcohol cessation, rather than HPV-specific interventions 1

• While HPV vaccination has shown efficacy in preventing cervical intraepithelial neoplasia and has potential to prevent HPV-attributed oropharyngeal cancer, there is insufficient evidence to recommend it specifically for esophageal cancer prevention 1

In conclusion, while HPV infection may be detected in some esophageal cancer cases, current high-quality evidence does not support HPV as a major causative factor in esophageal carcinogenesis, and the association likely reflects regional variations rather than a true etiologic relationship.