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Title: InterSCOPE Study: Associations Between Esophageal Squamous Cell Carcinoma and Human Papillomavirus Serological Markers
Authors: Sitas F; Malekzadeh R; Pawlita M; Dawsey SM; Waterboer T; Webb PM; Green AC; Hayward NK; Zaridze D; Holcatova I; Mates D; Egger S; Szeszenia-Dabrowska N; Ferro G; Janout V; Curado MP; Menezes AM; Koifman S; Islami F; Nasrollahzadeh D; Hu N; Goldstein AM; Urban MI; Gao Y; Ding T; Kamangar F; Taylor PR; Abnet CC; Boffetta P; O'Connell DL; Whiteman DC; Brennan P
Categories: Cancer Type - Oesophageal Cancer
Etiology - Endogenous Factors in the Origin and Cause of Cancer
Keywords: Australia; Proteins; Research; Risk; Smoking; cancer; Case-Control Studies; Confidence Intervals; epidemiology; HPV; methods; Odds Ratio; Other
Year: 2012
Journal Title: Journal of the National Cancer Institute
Volume: 104
Issue: 2
Page number start: 147
Page number end: 158
Abstract: Background The role of human papillomavirus (HPV) in the causation of esophageal squamous cell carcinoma is unclear. We examined the associations between esophageal squamous cell carcinoma and 28 centrally measured HPV serological markers in serum from six existing case-control studies conducted in regions with differing background risks of esophageal cancer. Methods We used centralized multiplex serology to test serum samples from 1561 case subjects and 2502 control subjects from six case-control studies for antibodies to the major HPV capsid protein (L1) and/or the early proteins E6 and/or E7 of eight high-risk, two low-risk, and four cutaneous HPV types. Study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using conditional logistic regression with adjustment for smoking, alcohol consumption, and other potential confounders. Pooled odds ratios and 95% confidence intervals were calculated using either a linear mixed-effects approach or a joint fixed-effects approach. All statistical tests were two-sided. Results We found statistically significant associations between esophageal squamous cell carcinoma and antibodies to E6 for HPV16 (OR = 1.89, 95% CI = 1.09 to 3.29, P = .023) and HPV6 (OR = 2.53, 95% CI = 1.51 to 4.25, P < .001) but not for other tested HPV types. There were no statistically significant associations between esophageal squamous cell carcinoma and antibodies to E7 for any of the tested HPV types. Simultaneous seropositivity for HPV16 E6 and E7 was rare (four case subjects, two control subjects; OR = 5.57, 95% CI = 0.90 to 34.35; P = .064). We also found statistically significant associations between esophageal squamous cell carcinoma and capsid antibodies for the high-risk mucosal type HPV33 L1 (OR = 1.30, 95% CI = 1.00 to 1.69; P = .047) and the low-risk mucosal types HPV6 (OR = 1.22, 95% CI = 1.05 to 1.42; P = .010) and HPV11 (OR = 1.30, 95% CI = 1.09 to 1.56, P = .0036). Conclusions We found limited serological evidence of an association between esophageal squamous cell carcinoma and HPV in the populations studied. Although HPV does not appear to be an important risk factor for esophageal squamous cell carcinoma, we cannot exclude the possibility that certain HPV types may be involved in a small subset of cancers
Programme: Cancer Causes
Division: Cancer Research Division
Funding Body: The InterSCOPE collaboration was partially funded by the intramural research programs of the US National Cancer Institute; the German Cancer Research Center; and Cancer Council New South Wales, Australia; and by grants from the Deutsche Krebshilfe. Institutions who funded the field work of the original studies were Brazilian Multicentric Case–Control Study: European Commission (grant no IC18-CT97-0222); Central and Eastern European Case–Control Study: World Cancer Research Fund, European Commission (Contract No. IC15-CT98-0332); The Golestan Case–Control Study: Digestive Disease Research Center, Tehran University of Medical Sciences (Grant Number 82-603); The Australian Cancer Study: National Health and Medical Research Council (Program Grant No. 199600) (Australia); Johannesburg Cancer Case–Control Study: South African National Health Laboratory Service and Medical Research Council; University of the Witwatersrand; Cancer Research UK; Shanxi Case–Control Study: the US National Cancer Institute (Contract NO2-SC-66211).
DOI: 10.1093/jnci/djr499
URI: http://researchpubs.cancercouncil.com.au/cancercounciljspui/handle/1/1542
Appears in Collections:Research Articles

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