Association of GSTM1 and HPV16 with tumor recurrence in head and neck cancer Free

LB-112

An estimated 34,360 new cases and 7,550 deaths will occur in the U.S. from head and neck cancer in 2007, accounting for 3-5% of all malignancies. Approximately 90% of head and neck cases are squamous in origin. Two distinct etiologies for head and neck squamous cell carcinoma (HNSCC) are proposed. Tobacco and alcohol exposure are the primary risk factors, while human papillomavirus (HPV) is associated with approximately 25% of HNSCC, predominantly HPV16. HNSCC patients have a poor 5-year survival rate (59%) and a high recurrence risk. However, patients with HPV-positive HNSCC who express p16 protein have an improved outcome. GSTM1 is involved in detoxification of carcinogens found in tobacco smoke, thus affecting tobacco-associated head and neck cancer risk. We report a retrospective study examining the association of GSTM1 genotype and HPV16 status with recurrence in HNSCC. HPV and GSTM1 status was determined using polymerase chain reaction (PCR) techniques. In 109 HNSCC patients, 26% (28/109) were HPV16 positive, and 58% (63/109) expressed the GSTM1 null genotype. HPV16+ tumors were more likely to carry GSTM1 deletion (68% GSTM1 null vs. 32% GSTM1 wt). When compared to patients with HPV-/GSTM1 wt tumors, patients with HPV+/GSTM1 wt tumors were more than two times more likely to recur (OR = 2.4, 95% CI = 0.7-8.2) while patients with HPV+/GSTM1 null tumors were less likely to recur (OR = 0.5, 95% CI = 0.2-1.6) and no difference in recurrence was observed for HPV-/GSTM1 null patients (OR = 1.2, 95% CI = 0.5-2.7). The expression of p16 in an HPV+ tumor is a surrogate marker for HPV E7 oncoprotein expression. Among the patients that did not have tumor recurrence, 56% (5/9) of the HPV+/GSTM1 null patients were also positive for p16 expression. In contrast, 75% (3/4) of the HPV+/GSTM1 null patients were negative for p16 expression. Two and 5-year recurrence rates were 20% for the HPV+/GSTM1 null patients, versus 34% and 49% respectively for others (p = 0.11). Our data suggest two independent pathways affecting HNSCC outcome. The reduced recurrence risk among HPV+/GSTM1 null patients is related to HPV infection, as indicated by p16 expression.