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Mucosal alpha‐papillomaviruses are not associated with esophageal squamous cell carcinomas: Lack of mechanistic evidence from S outh A frica, C hina and I ran and from a world‐wide meta‐analysis
Author(s) -
Halec Gordana,
Schmitt Markus,
Egger Sam,
Abnet Christian C.,
Babb Chantal,
Dawsey Sanford M.,
Flechtenmacher Christa,
Gheit Tarik,
Hale Martin,
Holzinger Dana,
Malekzadeh Reza,
Taylor Philip R.,
Tommasino Massimo,
Urban Margaret I.,
Waterboer Tim,
Pawlita Michael,
Sitas Freddy
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29911
Subject(s) - genotyping , biology , cancer research , downregulation and upregulation , hpv infection , antibody , messenger rna , virology , cancer , microbiology and biotechnology , immunology , genotype , gene , cervical cancer , genetics
Epidemiological and mechanistic evidence on the causative role of human papillomaviruses (HPV) in esophageal squamous cell carcinoma (ESCC) is unclear. We retrieved alcohol‐ and formalin‐fixed paraffin‐embedded ESCC tissues from 133 patients seropositive for antibodies against HPV early proteins, from high‐incidence ESCC regions: South Africa, China and Iran. With rigorous care to prevent nucleic acid contamination, we analyzed these tissues for the presence of 51 mucosotropic human alpha‐papillomaviruses by two sensitive, broad‐spectrum genotyping methods, and for the markers of HPV‐transformed phenotype: (i) HPV16/18 viral loads by quantitative real‐time PCR, (ii) type‐specific viral mRNA by E6*I/E6 full‐length RT‐PCR assays and (iii) expression of cellular protein p16 INK4a . Of 118 analyzable ESCC tissues, 10 (8%) were positive for DNA of HPV types: 16 (4 tumors); 33, 35, 45 (1 tumor each); 11 (2 tumors) and 16, 70 double infection (1 tumor). Inconsistent HPV DNA+ findings by two genotyping methods and negativity in qPCR indicated very low viral loads. A single HPV16 DNA+ tumor additionally harbored HPV16 E6*I mRNA but was p16 INK4a negative (HPV16 E1 seropositive patient). Another HPV16 DNA+ tumor from an HPV16 E6 seropositive patient showed p16 INK4a upregulation but no HPV16 mRNA. In the tumor tissues of these serologically preselected ESCC patients, we did not find consistent presence of HPV DNA, HPV mRNA or p16 INK4a upregulation. These results were supported by a meta‐analysis of 14 other similar studies regarding HPV‐transformation of ESCC. Our study does not support the etiological role of the 51 analyzed mucosotropic HPV types in the ESCC carcinogenesis.