Case-control study of human papillomavirus and oropharyngeal cancer.
BACKGROUND
Substantial molecular evidence suggests a role for human papillomavirus (HPV) in the pathogenesis of oropharyngeal squamous-cell carcinoma, but epidemiologic data have been inconsistent.


METHODS
We performed a hospital-based, case-control study of 100 patients with newly diagnosed oropharyngeal cancer and 200 control patients without cancer to evaluate associations between HPV infection and oropharyngeal cancer. Multivariate logistic-regression models were used for case-control comparisons.


RESULTS
A high lifetime number of vaginal-sex partners (26 or more) was associated with oropharyngeal cancer (odds ratio, 3.1; 95% confidence interval [CI], 1.5 to 6.5), as was a high lifetime number of oral-sex partners (6 or more) (odds ratio, 3.4; 95% CI, 1.3 to 8.8). The degree of association increased with the number of vaginal-sex and oral-sex partners (P values for trend, 0.002 and 0.009, respectively). Oropharyngeal cancer was significantly associated with oral HPV type 16 (HPV-16) infection (odds ratio, 14.6; 95% CI, 6.3 to 36.6), oral infection with any of 37 types of HPV (odds ratio, 12.3; 95% CI, 5.4 to 26.4), and seropositivity for the HPV-16 L1 capsid protein (odds ratio, 32.2; 95% CI, 14.6 to 71.3). HPV-16 DNA was detected in 72% (95% CI, 62 to 81) of 100 paraffin-embedded tumor specimens, and 64% of patients with cancer were seropositive for the HPV-16 oncoprotein E6, E7, or both. HPV-16 L1 seropositivity was highly associated with oropharyngeal cancer among subjects with a history of heavy tobacco and alcohol use (odds ratio, 19.4; 95% CI, 3.3 to 113.9) and among those without such a history (odds ratio, 33.6; 95% CI, 13.3 to 84.8). The association was similarly increased among subjects with oral HPV-16 infection, regardless of their tobacco and alcohol use. By contrast, tobacco and alcohol use increased the association with oropharyngeal cancer primarily among subjects without exposure to HPV-16.


CONCLUSIONS
Oral HPV infection is strongly associated with oropharyngeal cancer among subjects with or without the established risk factors of tobacco and alcohol use.
D'Souza
Gypsyamber
G
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.
Kreimer
Aimee R
AR
Viscidi
Raphael
R
Pawlita
Michael
M
Fakhry
Carole
C
Koch
Wayne M
WM
Westra
William H
WH
Gillison
Maura L
ML
D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects / Q000453:epidemiology; D052685:Alphapapillomavirus / Q000302:isolation & purification; D000914:Antibodies, Viral / Q000097:blood; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000473:pathology / Q000821:virology*; D016022:Case-Control Studies; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D017403:In Situ Hybridization; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000821:virology; D015999:Multivariate Analysis; D009910:Oral Hygiene; D009959:Oropharyngeal Neoplasms / Q000209:etiology / Q000473:pathology / Q000821:virology*; D030361:Papillomavirus Infections / Q000150:complications*; D012307:Risk Factors; D012725:Sexual Behavior; D012907:Smoking / Q000009:adverse effects / Q000453:epidemiology
D000914:Antibodies, Viral; D004279:DNA, Viral