Serologic evidence of herpes simplex virus 1 infection and oropharyngeal cancer risk

In vitro and animal models suggest that the herpes simplex virus 1 (HSV1) may contribute to the development of oropharyngeal squamous cell carcinoma (OSCC). To determine whether the risk of OSCC is related to infection with HSV1 in humans, we recruited 260 patients from 18 to 65 years old who were newly diagnosed with OSCC between 1990-1995 while residing in three western Washington State counties. For comparison, we recruited at random 445 controls frequency matched to cases on age and sex. Participants completed in-person interviews and provided serum samples that were tested for antibody response to HSV1. After adjusting for sex, cigarette smoking, alcohol consumption, age, and income, HSV1 antibody positivity was associated with a slightly increased risk of OSCC [adjusted odds ratio (OR), 1.3; 95% confidence interval (CI), 0.9-2.0]. The adjusted association between HSV1 antibody positivity 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 association between HSV1 infection and OSCC was similarly modified by evidence of HPV infection but no evidence of effect modification with alcohol consumption. This population-based study suggests that HSV1 may enhance the development of OSCC in individuals who are already at increased risk of the disease because of cigarette smoking or HPV infection.