In vitro and animal models suggest that the herpes simplex virus 1 (HSV1) m
ay contribute to the development of oropharyngeal squamous cell carcinoma (
OSCC). To determine whether the risk of OSCC is related to infection with H
SV1 in humans, we recruited 260 patients from 18 to 65 years old who were n
ewly diagnosed with OSCC between 1990-1995 while residing in three western
Washington State counties. For comparison, we recruited at random 445 contr
ols frequency matched to cases on age and sex. Participants completed in-pe
rson interviews and provided serum samples that were tested for antibody re
sponse to HSV1. After adjusting for sex, cigarette smoking, alcohol consump
tion, age, and income, HSV1 antibody positivity was associated with a sligh
tly increased risk of OSCC [adjusted odds ratio (OR), 1.3; 95% confidence i
nterval (CI), 0.9-2.0]. The adjusted association between HSV1 antibody posi
tivity and OSCC risk among those who were current cigarette smokers (OR, 4.
2; CI, 2.4-7.1) was stronger than would be predicted based on the additive
combination of smoking alone (OR, 2.3; CI, 1.2-4.2) and HSV1 seropositivity
alone (OR, 1.0; CI, 0.6-1.7). There was suggestive evidence that the assoc
iation between HSV1 infection and OSCC was similarly modified by evidence o
f HPV infection but no evidence of effect modification with alcohol consump
tion. This population-based study suggests that HSV1 may enhance the develo
pment of OSCC in individuals who are already at increased risk of the disea
se because of cigarette smoking or BPV infection.