Alpha human papillomavirus (α-HPV) infection (overwhelmingly HPV-16) is an established cause of head and neck squamous cell carcinoma (HNSCC), predominantly oropharyngeal cancer (OPC).1 Although this is a widely accepted causal association, a critical piece of evidence has been missing: a link between oral HPV infection and subsequent risk of HNSCC. In this issue of JAMA Oncology, Agalliu et al2 report findings from a prospective investigation of oral HPV infection (ie, HPV DNA detection in oral samples) and HNSCC risk.2 After analyzing 132 HNSCC cases and 396 controls nested within 2 prospective cohorts, the authors found that oral HPV-16 DNA detection was associated with a 22-fold increase in OPC risk. These data are remarkably consistent with risk estimates from numerous case-control studies.1 However, the study by Agalliu et al contributes to the existing body of evidence by supporting a temporal association between HPV exposure and HNSCC. Previous nested case-control studies have observed serological measures of HPV exposure (eg, seropositivity to HPV-16 viral capsid or E6 and/or E7 oncoproteins) to increase risk of OPC.1 By linking oral HPV detection directly to HNSCC risk, the Agalliu data have important implications for the use of oral HPV detection for OPC screening.1
Rollison DE, Gillison ML. The Alpha, Beta, Gammas of Oral Human Papillomavirus Infection and Head and Neck Cancer Risk. JAMA Oncol. 2016;2(5):606–607. doi:10.1001/jamaoncol.2015.5686
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