Esophageal cancer is the eighth most common cancer, which shows remarkable regional variations in incidence rates. The etiology of the most common type of esophageal cancer - esophageal squamous cell carcinoma (ESCC), is undisputedly multifactorial and includes the synergistic action of Group 1 human carcinogens: tobacco, betel quid with or without added tobacco, alcohol and acetaldehyde associated with alcoholic beverages. According to the robust and strong data, which have accumulated over last 30 years, carcinogenic HPV types from the α-PV genus, mainly HPV-16, should also be seriously considered as etiological agents for a subset of ESCC.
Recent meta-analyses and our literature update identified more than 200 studies with over 13,000 cases of ESCC analyzed for the presence of HPV to date. Approximately one third of ESCC specimens tested HPV positive, but HPV DNA detection rates were highly variable in different geographical areas of the world. A meta-analysis of case-control studies investigating the etiological role of HPV in the development of ESCC also supports an HPV-ESCC association for fraction of ESCC. Our literature review showed that the two most important vaccine-preventable HPV types: HPV-16 and HPV-18 have been the most commonly identified HPV types in ESCC specimens in both low-incidence and high-incidence settings. Prophylactic vaccination with all three currently available HPV vaccines could theoretically prevent more that 70% of all alpha-HPV DNA positive ESCC, although only if proved to work against non-genital HPV-related cancers or their precursors.
In order to provide conclusive evidence that HPV is a definitive causative factor in subset of ESCCs, we need more studies. A well-designed large international case-control study with sufficient power indisputably to ascertain HPV rates in ESCC cases compared to controls without ESCC using a uniform HPV testing methodology is the most practical way forward.