Role of Human Papillomaviruses in Esophageal Carcinoma: An Updated Systematic Review from 1982 to 2013

Abstract

Tobacco, alcohol and betel quid are known etiological agents of esophageal squamous cell carcinoma (ESCC). A meta-analysis in 2012 and a literature update (1982–August 2013) identified 159 studies with a total of 11,310 ESCCs tested for the presence of human papillomaviruses (HPVs). HPV DNA was present in 30.3% of fESCCs, with substantial geographic differences. A recent meta-analysis of 21 case–control studies investigating the HPV–ESCC association showed that HPVs increase the risk of ESCC at least threefold. Vaccine-preventable HPV-16 and HPV-18 are the most commonly identified HPV types in ESCC in both low- and high-incidence settings. HPVs should now be seriously considered as etiological agents for at least a subset of ESCC, and more studies are needed to provide conclusive evidence that HPVs cause ESCC.

A systematic literature review of studies reporting human papillomavirus (HPV) prevalence in esophageal carcinoma over 36 years (1982–2017)

“…Interestingly, the HPV prevalence rate primarily depended on the HPV detection method used, being the highest using L1 serology (32.2%, 95% CI 15.4-49.0%), followed by IHC (30.4%, 95% CI 18.5-42.3%), PCR (27.7%, 95% CI 23.4-32.0%), ISH (24.3%, 95% CI 15.9-32.6%), and Southern/slot/dot blot (17.6%, 95% CI 6.1-29.2%). In accordance with previous studies (7,9,(22)(23)(24)34), the detection rate of HPV varied across different geographical regions, with the HPV prevalence ranging from 15.6% (95% CI 7.3-23.8%) in Europe/Australia to 31.4% (95% CI 27.4-35.4%) in Asia. Differences in HPV prevalence were also observed between studies that were published prior to 1990 (10.3%, 95% CI 11.4-32.1%), between 1990 and 1999 (20.4%, 95% CI 14.9-25.9%), and after 2000 (31.0%, 95% CI 26.7-35.2%), and between studies including fewer than 60 ESCC cases (27.2%, 95% CI 22.6-31.8%) and studies with more than 60 ESCC cases (26.1%, 95% CI 21.1-31.1%).…”

“…Differences in HPV prevalence were also observed between studies that were published prior to 1990 (10.3%, 95% CI 11.4-32.1%), between 1990 and 1999 (20.4%, 95% CI 14.9-25.9%), and after 2000 (31.0%, 95% CI 26.7-35.2%), and between studies including fewer than 60 ESCC cases (27.2%, 95% CI 22.6-31.8%) and studies with more than 60 ESCC cases (26.1%, 95% CI 21.1-31.1%). Similar to previous literature reviews (7,(24)(25)(26)28), HPV16 was the predominant HPV type, with an estimated prevalence of 18.5% (95% CI 14.2-22.8%), when considering studies using PCR as an HPV-detection method (33).…”

“…In 2014, Li et al published a systematic review with a metaanalysis that assessed 8,990 ESCC cases obtained from 76 studies (25). In addition to the overall HPV prevalence in ESCCs, which was 22.2% (95% CI 18.3-26.7%), the study also provided a typespecific HPV prevalence, with HPV16 being the most frequently detected HPV type, with an overall prevalence of 11.4% (95% CI 8.2-15.7%), similar to what was observed in previous studies (7,24). In line with the previous studies (9, 23, 24), Li et al also observed a significant association between ESCC and HPV infection (OR 3.32, 95% CI 2.26-4.87) and ESCC and HPV16 infection (OR 3.52, 95% CI 2.04-6.07) (25).…”

“…The geographical differences in HPV prevalence among ESCC cases observed in previous studies (7,9,22) were subsequently also confirmed in the meta-analysis by Liu et al, which critically addressed a total of 145 ESCC studies published between 1982 and 2012 (23). Among 6,912 ESCC cases, the HPV prevalence was estimated at 38.9% and was statistically significantly higher in China (44.0%) in comparison to other regions (31.2%) (p < 0.05).…”

“…The calculated combined HPV16/18 prevalence was 23.3%, with HPV16 and HPV18 found in 16.3% and 2.7% of ESCCs investigated, respectively. Moreover, the combined HPV16/18 prevalence among all HPV-positive cases was estimated at 73.7% (7).…”