InterSCOPE study: Associations between esophageal squamous cell carcinoma and human papillomavirus serological markers.
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.
Cancer Council NSW, Cancer Epidemiology Research Unit, Sydney, NSW, Australia. freddys@nswcc.org.au
Freddy
F
Sitas
Sam
S
Egger
Margaret I
MI
Urban
Philip R
PR
Taylor
Christian C
CC
Abnet
Paolo
P
Boffetta
Dianne L
DL
O'Connell
David C
DC
Whiteman
Paul
P
Brennan
Reza
R
Malekzadeh
Michael
M
Pawlita
Sanford M
SM
Dawsey
Tim
T
Waterboer
D000328:Adult; D000368:Aged; D052685:Alphapapillomavirus / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood*; D000956:Antigens, Viral / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000821:virology*; D016022:Case-Control Studies; D016001:Confidence Intervals; D015986:Confounding Factors, Epidemiologic; D004938:Esophageal Neoplasms / Q000821:virology*; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology; D052161:Human papillomavirus 18 / Q000276:immunology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D030361:Papillomavirus Infections / Q000150:complications* / Q000175:diagnosis / Q000821:virology; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D014412:Tumor Virus Infections / Q000150:complications
D000914:Antibodies, Viral; D000956:Antigens, Viral