Serologic association between human papillomavirus type 16 infection and esophageal cancer in Shaanxi Province, China.
BACKGROUND
The existence of large geographic variations in the prevalence of esophageal cancer in some countries, such as China, indicates that environmental risk factors may be important in the development of this disease. Some studies have implicated genital-mucosal strains of human papillomaviruses (HPVs) in the etiology of this cancer.


OBJECTIVE
We conducted a case-control study in Shaanxi Province, China, an area with a population at high risk for esophageal cancer, to assess the association of this disease with infection by HPV type 16 (HPV16), the most common cancer-associated genital-mucosal HPV type.


METHODS
Ninety individuals with esophageal cancer and 121 cancer-free control subjects were identified among the patients in two hospitals in Xi'an, Shaanxi Province. The control subjects were matched to the case patients on the basis of age and sex. Blood specimens were drawn from all study subjects, and serum was isolated by routine methods. The presence of HPV16 antibodies in serum samples was determined by use of an enzyme-linked immunosorbent assay (ELISA) that used baculovirus-derived HPV16 virus-like particles as the antigen. A similar ELISA that used bovine papillomavirus type 1 (BPV1) virus-like particles as the antigen controlled for the specificity of HPV16 seroreactivity. Data from the HPV16 and the BPV1 assays were normalized with respect to results obtained in each assay with a control serum of known HPV16 seroreactivity. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to examine the association between HPV16 seroreactivity and esophageal cancer. Reported P values are two-sided.


RESULTS
The mean seroreactivity to HPV16 virus-like particles was significantly higher for the cancer patients than for the control subjects (mean value +/- standard deviation = 0.85 +/- 0.22 versus 0.74 +/- 0.18; P<.0001). When the cancer patients and control subjects were compared by sex and age groups, the differences in mean seroreactivity remained statistically significant. The difference in mean seroreactivity to BPV1 virus-like particles between cancer patients and control subjects was not statistically significant (0.81 +/- 0.28 versus 0.88 +/- 0.32; P = .12); this result was not altered when sex and age groups were compared. By use of a cutoff point for HPV16 seropositivity that was established in studies of cervical neoplasia, 24% of the cancer patients were seropositive compared with 7% of the control subjects, yielding a sex- and age-adjusted OR of 4.5 (95% CI = 1.8-11.9). In general, the OR for esophageal cancer increased with increasing HPV16 seroreactivity.


CONCLUSIONS
HPV16 infection may be a risk factor for esophageal cancer. Further studies of the association between HPV16 infection and the incidence of esophageal cancer are needed.
Han
C
C
Laboratory of Cellular Oncology, Division of Basic Sciences, National Cancer Institute, Bethesda, MD, USA.
Qiao
G
G
Hubbert
N L
NL
Li
L
L
Sun
C
C
Wang
Y
Y
Yan
M
M
Xu
D
D
Li
Y
Y
Lowy
D R
DR
Schiller
J T
JT
D000914:Antibodies, Viral / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000821:virology; D016022:Case-Control Studies; D002681:China; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000276:immunology / Q000821:virology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000150:complications* / Q000276:immunology; D014412:Tumor Virus Infections / Q000150:complications* / Q000276:immunology
D000914:Antibodies, Viral