Investigating the association between SLPI and AnxA2 expression, smoking behavior, and HPV infection in HNSCC, we initially showed in ex vivo experiments that exposure to nicotine, a major component of tobacco, leads to an increase in SLPI expression in the human nasal mucosa, revealing the possible mechanisms underlying the consistent observation that smokers develop mostly HPV-negative HNSCC, whereas non-smokers develop HPV-positive HNSCC (28). Here, ANXA2 is linked to head and neck squamous cell carcinoma.