XPA–A Biomarker With Potential Prognostic Value in Patients With Oropharyngeal Head and Neck Squamous Cell Carcinoma

Abstract

Platinum-based chemotherapy resistance has been under investigation for a long time, looking at the nucleotide excision repair (NER) pathway, which is responsible for DNA adduct repair. One of the participating proteins in that pathway is XPA. There is little information about this protein regarding its prognostic value in patients with head and neck squamous cell carcinoma (HNSCC). Therefore, we investigated XPA expression as a prognostic factor by retrospectively looking at overall survival, time to recurrence, and correlation with clinical parameters. Tissue microarrays were constructed from 453 cases of HNSCC including 222 oral (49%), 126 pharyngeal (27.8%), and 105 laryngeal (23.2%) tumors. Two hundred ninety-three tumor blocks were evaluable for XPA immunohistochemistry. Expression levels were dichotomized into a high and low XPA expressing group followed by a comparison of age, gender, TNM status, grading, and UICC stage. Outcomes for overall survival and time to recurrence were analyzed by using the Kaplan-Meier method and performed for different subsites of the head and neck. Analysis of overall survival and time to recurrence showed no difference between both expression levels of XPA in the overall patient cohort. However, superior overall survival in patients with oropharyngeal SCC and a high XPA expression could be observed (P=.0386). Looking at SCCs of the oral cavity, a trend toward an inferior overall survival in patients with a high XPA expression was seen, whereas investigations in the hypopharynx and larynx showed no significant differences between high and low XPA expressing tumors. Looking generally at gender, M stage, and grading, no statistical correlation was found. Analyzing T and N stage in all tumors, a trend toward a lower XPA expression in advanced tumors (>pT4 P=.0543 and >pN1 P=.0546) could be seen. This trend was confirmed by statistical lower expression of XPA in patients with UICC stage IV looking at the overall patient cohort (P=.035). The shown results suggest that XPA might be a novel predictive marker for overall survival in patients with oropharyngeal SCC with a superior survival in tumors with a high XPA expression. Furthermore, this study shows that subsites in the head and neck will have to be looked at separately in the future to determine the predictive value of biomarkers for therapy outcome and pretherapeutic risk stratification of patients. To increase statistical power of this study and to evaluate the effect on platinum-based chemotherapy resistance, further studies with even larger patient cohorts will be needed and are ongoing.