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No role for human papillomavirus in esophageal squamous cell carcinoma in China
Author(s) -
Koshiol Jill,
Wei WenQiang,
Kreimer Aimee R.,
Chen Wen,
Gravitt Patti,
Ren JianSong,
Abnet Christian C.,
Wang JianBing,
Kamangar Farin,
Lin DongMei,
von KnebelDoeberitz Magnus,
Zhang Yu,
Viscidi Raphael,
Wang GuoQing,
Gillison Maura L.,
Roth Mark J.,
Dong ZhiWei,
Kim Esther,
Taylor Philip R.,
Qiao YouLin,
Dawsey Sanford M.
Publication year - 2010
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.25023
Subject(s) - human papillomavirus , esophageal squamous cell carcinoma , dna , carcinoma , biology , polymerase chain reaction , carcinogen , cancer research , pathology , gene , microbiology and biotechnology , medicine , genetics
Certain regions of China have high rates of esophageal squamous cell carcinoma (ESCC). Previous studies of human papillomavirus (HPV), a proposed causal factor, have produced highly variable results. We attempted to evaluate HPV and ESCC more definitively using extreme care to prevent DNA contamination. We collected tissue and serum in China from 272 histopathologically‐confirmed ESCC cases with rigorous attention to good molecular biology technique. We tested for HPV DNA in fresh‐frozen tumor tissue using PCR with PGMY L1 consensus primers and HPV16 and 18 type‐specific E6 and E7 primers, and in formalin‐fixed paraffin‐embedded tumor tissue using SPF 10 L1 primers. In HPV‐positive cases, we evaluated p16 INK4a overexpression and HPV E6/E7 seropositivity as evidence of carcinogenic HPV activity. β‐globin, and thus DNA, was adequate in 98.2% of the frozen tumor tissues (267/272). Of these, 99.6% (95% confidence interval (CI) = 97.9–100.0%) were negative for HPV DNA by PGMY, and 100% (95% CI = 98.6–100%) were negative by HPV16/18 E6/E7 PCR. In the corresponding formalin‐fixed paraffin‐embedded tumor specimens, 99.3% (95% CI = 97.3–99.9%) were HPV negative by SPF 10 . By PGMY, 1 case tested weakly positive for HPV89, a noncancer causing HPV type. By SPF 10 , 2 cases tested weakly positive: 1 for HPV16 and 1 for HPV31. No HPV DNA‐positive case had evidence of HPV oncogene activity as measured by p16 INK4a overexpression or E6/E7 seropositivity. This study provides the most definitive evidence to date that HPV is not involved in ESCC carcinogenesis in China. HPV DNA contamination cannot be ruled out as an explanation for high HPV prevalence in ESCC tissue studies with less stringent tissue procurement and processing protocols.