Because p53 and p73 are associated with critical cellular processes and can be inactivated or degraded by the human papillomavirus (HPV) E6
oncoprotein, we investigated the combined effects of p53
codon 72 and p73 G4C14-to-A4T14 polymorphisms on the risk of HPV16-associated
oral cancer. We analyzed genotype data from 326 patients with
squamous cell carcinoma of the oral cavity or oropharynx and 349
cancer-free controls. We found that HPV16 seropositivity was associated with an increased risk of
oral cancer [adjusted odds ratio (OR), 3.42; 95% confidence interval (CI), 2.28-5.13], especially among never-smokers (adjusted OR, 8.20; 95% CI, 3.66-18.4) and subjects with variant genotypes [adjusted OR for p53
Arg/Pro + Pro/
Pro (Pro carriers), 5.00; 95% CI, 2.72-9.21; adjusted OR for p73 GC/AT + AT/AT (AT carriers), 3.83; 95% CI, 1.98-7.41]. HPV16 seropositivity was also associated with an significantly increased risk of
oral cancer in all three risk groups with combined genotypes [adjusted
ORs (95% CIs) were 2.28 (1.15-4.54) for p53
Arg/Arg and p73 GC/GC, the low-risk group; 3.97 (2.14-7.36) for p53
Arg/Arg and p73 AT carriers or p53 Pro carriers and p73 GC/GC, the medium-risk group and 5.11 (2.00-13.0) for p53 Pro carriers and p73 AT carriers, the high-risk group]. Moreover, HPV16-seropositive never-smokers in the high-risk group exhibited an approximately 11-fold greater risk of
oral cancer (adjusted OR, 11.3; 95% CI, 1.22-106.0) than did HPV16-seronegative never-smokers in the low-risk group. These findings suggest that the combined variants of p53 and p73 significantly increase the risk of HPV16-associated
oral cancer, especially among never-smokers.