The prevalence of viral agents in esophageal adenocarcinoma and Barrett’s esophagus: a systematic review

Kunzmann, Andrew T.; Graham, Suzanne R; McShane, Charlene M.; Doyle, J. S.; Tommasino, Massimo; Johnston, Brian T.; Jamison, Jackie; James, Jacqueline; McManus, Damian; Anderson, Lesley A.

doi:10.1097/meg.0000000000000868

Cited by 28 publications

(31 citation statements)

References 57 publications

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“…Another systematic review that included 19 studies concluded that the pooled prevalence of HPV in EAC was 13%. The authors suggested that the low prevalence rate may have been caused by small sample sizes and compromised detection methods . An important reason for why it is difficult to detect HPV DNA via PCR is the low viral load in glandular tissue, which is very much less than in the uterine cervix, anal canal, and oropharynx, which all consist of squamous epithelium.…”

Section: Hpv and Adenocarcinoma Of The Esophagusmentioning

confidence: 99%

“…The association of EBV with a subset of gastric adenocarcinomas and adenocarcinomas of the gastroesophageal junction has been well documented over the last few decades, and EBV positivity now also defines a specific molecular subtype of gastric adenocarcinoma that is highly distinct from EBV‐negative tumors . The association of EBV with esophageal carcinoma, however, is less clearly defined, as the relatively few studies on this matter show conflicting results . These discrepancies can be primarily attributed to the different methods used to detect EBV.…”

Section: The Role Of Ebv In Esophageal Cancermentioning

confidence: 99%

“…In contrast, direct evidence of EBV in individual tumor cells by ISH or immunohistochemistry is more specific, with the disadvantage of being less sensitive. Studies focusing on the detection of EBV within tumor cells suggest that EBV is not associated with EAC and conventional ESCC . However, the very rare squamous cell carcinoma variant of lymphoepithelial carcinoma or lymphoepithelioma‐like carcinoma has been shown to be associated with EBV infection in several studies .…”

Section: The Role Of Ebv In Esophageal Cancermentioning

confidence: 99%

“…The authors suggested that the low prevalence rate may have been caused by small sample sizes and compromised detection methods. 78 An important reason for why it is difficult to detect HPV DNA via PCR is the low viral load in glandular tissue, 79 which is very much less than in the uterine cervix, anal canal, and oropharynx, which all consist of squamous epithelium. It is well known that HPV has a predilection for squamous epithelium, though ISH analysis of HPV DNA and E6/E7 mRNA has clearly demonstrated viral tropism for esophageal glandular tissue ( Figs.…”

Section: Hpv and Adenocarcinoma Of The Esophagusmentioning

confidence: 99%

“…94,95 The association of EBV with esophageal carcinoma, however, is less clearly defined, as the relatively few studies on this matter show conflicting results. 78,96,97 These discrepancies can be primarily attributed to the different methods used to detect EBV. Older studies relying on PCR-based methods lack specificity, as EBVpositive lymphocytes are found in the majority of the adult population.…”

Section: Biological Background Of Ebv Infection In Gastrointestinal Cmentioning

confidence: 99%

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Risk factors for esophageal cancer: emphasis on infectious agents

El‐Zimaity

Pilato

Ringressi

et al. 2018

Annals of the New York Academy of Sciences

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Risk factors for esophageal cancer include genetic factors (such as tylosis) and infectious agents. A variety of organisms have been implicated in esophageal carcinogenesis, either directly or indirectly. In this review, we explore the normal esophageal flora and how it may be controlled, and also the variety of organisms that may affect esophageal carcinogenesis, either directly or indirectly. The organisms with potential direct effects in squamous cell carcinoma include human papillomavirus (HPV), Epstein-Barr virus, and polyoma viruses. Interestingly, HPV is now implicated in esophageal adenocarcinoma (EAC), not in its initiation but in the development of dysplasia, in which HPV33 in particular has been associated. Indirectly, Helicobacter pylori has been associated with EAC by, initially, causing increased acid secretion that increases acid reflux, and by reducing lower esophageal sphincter pressure, which increases gastroesophageal reflux; the latter increases the risk of Barrett's esophagus, and hence EAC. Conversely, subsequent atrophic gastritis may normalize that risk.

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Section: Hpv and Adenocarcinoma Of The Esophagusmentioning

confidence: 99%

Section: The Role Of Ebv In Esophageal Cancermentioning

confidence: 99%

Section: The Role Of Ebv In Esophageal Cancermentioning

confidence: 99%

Section: Hpv and Adenocarcinoma Of The Esophagusmentioning

confidence: 99%

Section: Biological Background Of Ebv Infection In Gastrointestinal Cmentioning

confidence: 99%

See 3 more Smart Citations

Risk factors for esophageal cancer: emphasis on infectious agents

El‐Zimaity

Pilato

Ringressi

et al. 2018

Annals of the New York Academy of Sciences

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Survival Rates for Patients With Barrett High-grade Dysplasia and Esophageal Adenocarcinoma With or Without Human Papillomavirus Infection

et al. 2018

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Key Points Question What is the prognostic significance of esophageal tumor human papillomavirus (HPV) status? Findings In this case-control study involving 142 patients with Barrett high-grade dysplasia and esophageal adenocarcinoma, HPV positivity was associated with a significantly improved disease-free survival compared with viral negativity. Recurrence and progression were reduced in the HPV-positive cohort as were distant metastasis and death from esophageal adenocarcinoma. Meaning Barrett high-grade dysplasia and esophageal adenocarcinoma in patients who are HPV positive have a favorable prognosis compared with viral-negative esophageal tumors and may benefit from treatment de-escalation.

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Human Papillomavirus Status and Esophageal Adenocarcinoma

Dhesy‐Thind

2018

JAMA Netw Open

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Esophageal cancer remains one of the most lethal malignant neoplasms, with an estimated 456 000 new cases worldwide and 400 000 deaths in 2012. 1 With the reduction in smoking rates, the incidence of squamous cell carcinoma of the esophagus has been decreasing in many developed nations. However, this is not the case for esophageal adenocarcinoma (EAC). 1 Environmental and lifestyle factors have been implicated, including a potential carcinogenic role of viral agents such as human papillomavirus (HPV). Rajendra et al 2 report on the prognosis of HPV status in a retrospective case-control study of 142 patients with Siewert class I or II high-grade dysplasia or EAC. The authors used a robust panel of HPV tests beyond standard HPV DNA and included markers of biologic viral activity, including overexpression of E6 and E7 messenger RNA, which is a more specific assay for oncoprotein detection and more relevant for malignant progression of the virus. Immunohistochemical staining for the tumor suppressor proteins p16 INK4A and p53 and TP53 gene sequencing were also conducted. Improved disease-free survival in those patients with HPV-positive Barrett high-grade dysplasia and EAC was demonstrated. This was most notable in both patients with HPV-positive cancers (hazard ratio, 0.33; 95% CI, 0.16-0.67; P = .002) and patients with transcriptionally active HPV-positive cancers (hazard ratio, 0.44; 95% CI, 0.22-0.88; P = .02). Mean disease-free survival was 40.3 months in the HPV-positive patient population compared with only 24.1 months in the HPV-negative group. Patients with HPV-positive cancers had reduced recurrence rates and distant metastases. From a pathological perspective, HPV-positive tumors had lower T stage and differentiation and more complete (R0) resections as well as fewer TP53 mutations, all factors that may independently contribute to a more favorable survival outcome. Whether this is a causal association remains unknown; ie, does HPV infection result in a more indolent malignant tumor, and does the presence of HPV in patient tissue samples identify a more favorable pathology? The authors rationalize that the prognostic findings of this cohort study justify investigation of HPV positivity as a predictive marker to treat selective patients with EAC with less intensive therapy. Given the dismal prognosis of this type of tumor and presence of conflicting studies, this is a rather significant inference. The role of HPV in the pathogenesis of cervical and other anogenital cancers has been recognized with a number of high-risk HPV genotypes implicated in carcinogenesis. 3 The viral oncogenes E6 and E7 have been consistently demonstrated in tumor samples and shown to downregulate tumor suppressor protein p53 and retinoblastoma proteins with impairment in cell cycle regulation. 4 The virus also has a putative role in initiation of tumorigenesis via activation of the Wnt/β-catenin signaling pathway. 5 Given the association of HPV with squamous cell malignant tumors of the head and neck 6 and anogenital tract, studies ...

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The prevalence of viral agents in esophageal adenocarcinoma and Barrett’s esophagus: a systematic review

Abstract: The prevalence of HPV and EBV in EAC is low compared with other viral-associated cancers, but may have been hampered by small sample sizes and detection methods susceptible to fixation processes. Additional research with adequate sample sizes and high-quality detection methods is required.

Cited by 28 publications

References 57 publications

Risk factors for esophageal cancer: emphasis on infectious agents

Risk factors for esophageal cancer: emphasis on infectious agents

Survival Rates for Patients With Barrett High-grade Dysplasia and Esophageal Adenocarcinoma With or Without Human Papillomavirus Infection

Human Papillomavirus Status and Esophageal Adenocarcinoma

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