Abstract
Objective
The human papillomavirus (HPV) is implicated in the pathogenesis of several cancers among humans. The role of HPV as one of the etiological agents in esophageal carcinogenesis is partially unknown. We assessed whether the available evidence supports the association of HPV with risk and prognosis in patients with esophageal squamous cell carcinomas (ESCCs).
Design
For this systematic review and meta-analysis, PubMed, Embase, Cochrane Library, and SCOPUS were searched up to February 2021. The included studies were prospective or retrospective studies that evaluated the incidence, risk, and prognosis of HPV-16/18–related ESCCs in adult subjects. The primary outcome was the incidence rate of ESCC in HPV-16/18 carriers. Secondary outcomes included the risk of ESCCs compared with healthy HPV-16/18 carriers (expressed as odds ratios [ORs] with 95% confidence intervals [CIs]) and the survival of HPV + versus HPV- ESCCs.
Results
The search identified 1649 unique citations, of which 145 met the inclusion criteria and were included in the pooled analysis (16,484 patients). The pooled HPV prevalence in ESCCs was 18.2% (95% CI 15.2–21.6%; P < 0.001). A significantly increased ESCC risk was associated with HPV infection (OR = 3.81; 95% CI 2.84–5.11; P < 0.001). Main limitation were methods of HPV detection (DNA only), race of populations included (mainly Asiatic countries) and lack of adjustment for other prognostic factors.
Conclusions
The findings suggest that HPV-16/18 is detectable in about 1 on 5 cases of ESCC with different prevalences across the world. It is moderately but significantly associated with a diagnosis of ESCC. Further epidemiological studies are needed to confirm and increase the current knowledge of the subject.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Chang F, Syrjänen S, Tervahauta A, Kurvinen K, Wang L, Syrjänen S (1994) Frequent mutations of p53 gene in oesophageal squamous cell carcinomas with and without human papillomavirus (HPV) involvement suggest the dominant role of environmental carcinogens in oesophageal carcinogenesis. Br J Cancer 70(2):346–351. https://doi.org/10.1038/bjc.1994.305
de Sanjose S, Quint WGV, Alemany L et al (2010) Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. https://doi.org/10.1016/S1470-2045(10)70230-8
D’Souza G, Kreimer AR, Viscidi R et al (2007) Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. https://doi.org/10.1056/nejmoa065497
El-Zimaity H, Di Pilato V, Ringressi MN et al (2018) Risk factors for esophageal cancer: emphasis on infectious agents. Ann NY Acad Sci. https://doi.org/10.1111/nyas.13858
Engel LS, Chow WH, Vaughan TL et al (2003) Population attributable risks of esophageal and gastric cancers. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djg047
Eslick GD (2010) Infectious causes of esophageal cancer. Infect Dis Clin North Am. https://doi.org/10.1016/j.idc.2010.08.001
Freedman ND, Abnet CC, Leitzmann MF et al (2007) A prospective study of tobacco, alcohol, and the risk of esophageal and gastric cancer subtypes. Am J Epidemiol. https://doi.org/10.1093/aje/kwm051
Garland SM (2002) Human papillomavirus update with a particular focus on cervical disease. Pathology. https://doi.org/10.1080/00313020212469
Georgantis G, Syrakos T, Agorastos T et al (2015) Detection of human papillomavirus DNA in esophageal carcinoma in Greece. World J Gastroenterol. https://doi.org/10.3748/wjg.v21.i8.2352
Gillison ML, D’Souza G, Westra W et al (2008) Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djn025
Gillison ML, Broutian T, Pickard RKL et al (2012) Prevalence of oral HPV infection in the United States, 2009–2010. JAMA. https://doi.org/10.1001/jama.2012.101
Integrated genomic characterization of oesophageal carcinoma. Cancer Genome Atlas Research Network Nature 541(7636):169–175. https://doi.org/10.1038/nature20805. Accessed 12 Jan 2017
Kamath AM, Wu TT, Heitmiller R, Daniel R, Shah KV (2000) Investigation of the association of esophageal carcinoma with human papillomaviruses. Dis Esophagus. https://doi.org/10.1046/j.1442-2050.2000.00098.x
Koh JS, Lee SS, Baek HJ, Kim YI (2008) No association of high-risk human papillomavirus with esophageal squamous cell carcinomas among Koreans, as determined by polymerase chain reaction. Dis Esophagus. https://doi.org/10.1111/j.1442-2050.2007.00726.x
Kok TC, Nooter K, Tjong-A-Hung SP, Smits HL, Ter Schegget J (1997) No evidence of known types of human papillomavirus in squamous cell cancer of the oesophagus in a low-risk area. Eur J Cancer. https://doi.org/10.1016/S0959-8049(97)85984-9
Li Y, Yang H, Cao J (2011) Association between alcohol consumption and cancers in the chinese population-a systematic review and meta-analysis. PLoS ONE. https://doi.org/10.1371/journal.pone.0018776
Li X, Gao C, Yang Y et al (2014) Systematic review with meta-analysis: the association between human papillomavirus infection and oesophageal cancer. Aliment Pharmacol Ther. https://doi.org/10.1111/apt.12574
Michaelsen SH, Larsen CG, Von Buchwald C (2014) Human papillomavirus shows highly variable prevalence in esophageal squamous cell carcinoma and no significant correlation to p16INK4a overexpression: a systematic review. J Thorac Oncol. https://doi.org/10.1097/JTO.0000000000000166
Petrick JL, Wyss AB, Butler AM et al (2014) Prevalence of human papillomavirus among oesophageal squamous cell carcinoma cases: systematic review and meta-analysis. Br J Cancer. https://doi.org/10.1038/bjc.2014.96
Qi Z, Jiang Q, Yang J et al (2013) Human papillomavirus (HPV) infection and the risk of esophageal squamous cell carcinoma. Dis Esophagus 26(1):61–67. https://doi.org/10.1111/j.1442-2050.2012.01334.x
Rajendra S, Pavey D, McKay O, Merrett N, Gautam SD (2020) Human papillomavirus infection in esophageal squamous cell carcinoma and esophageal adenocarcinoma: a concise review. Ann N Y Acad Sci. https://doi.org/10.1111/nyas.14509
Sonawane K, Suk R, Chiao EY et al (2017) Oral human papillomavirus infection: Differences in prevalence between sexes and concordance with genital human papillomavirus infection, NHANES 2011 to 2014. Ann Intern Med. https://doi.org/10.7326/M17-1363
Stoner GD, Gupta A (2001) Etiology and chemoprevention of esophageal squamous cell carcinoma. Carcinogenesis. https://doi.org/10.1093/carcin/22.11.1737
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD (2008) MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies. JAMA 283:2008
Tran GD, Di SX, Abnet CC et al (2005) Prospective study of risk factors for esophageal and gastric cancers in the Linxian General Population Trial cohort in China. Int J Cancer. https://doi.org/10.1002/ijc.20616
Tsikouras P, Zervoudis S, Manav B et al (2016) Cervical cancer: screening, diagnosis and staging. J Buon 21:320
Wells G, Shea B, O'Connell D et al (2012) The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses.https://doi.org/10.2307/632432
Wong MYW, Wang B, Yang A, Khor A, Xuan W, Rajendra S (2018) Human papillomavirus exposure and sexual behavior are significant risk factors for Barrett’s dysplasia/esophageal adenocarcinoma. Dis Esophagus 31(12):1–7.https://doi.org/10.1093/dote/doy051
Yong F, Xudong N, Lijie T (2013) Human papillomavirus types 16 and 18 in esophagus squamous cell carcinoma: a meta-analysis. Ann Epidemiol.https://doi.org/10.1016/j.annepidem.2013.07.002
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
None.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Petrelli, F., De Santi, G., Rampulla, V. et al. Human papillomavirus (HPV) types 16 and 18 infection and esophageal squamous cell carcinoma: a systematic review and meta-analysis. J Cancer Res Clin Oncol 147, 3011–3023 (2021). https://doi.org/10.1007/s00432-021-03738-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-021-03738-9