Gene Expression Characterization of HPV Positive Head and Neck Cancer to Predict Response to Chemoradiation

Abstract

Human papillomavirus (HPV) has been shown to have a causal role in the development of head and neck squamous cell carcinoma. While HPV-positive head and neck cancer is associated with a better response to treatment in the majority of patients, there is a subset who does not respond favorably to current therapy. Identification of these patients could prevent unnecessary morbidity and indicate the need for alternative therapeutic options. Tissue samples were obtained from 19 patients with HPV-positive head and neck squamous carcinoma treated with chemoradiation therapy. HPV status was confirmed by polymerase chain reaction analysis through detection of HPV16 E7 in both DNA and RNA. RNA was isolated from tissue samples and subjected to microarray gene expression analysis. In addition to identification of potential genetic biomarkers (including LCE3D, KRTDAP, HMOX1, KRT19, MDK, TSPAN1), differentially expressed genes associated with genomic stability, cell cycle, and DNA damage were detected between responders and non-responders. These results were further validated with publicly available gene expression studies. This pilot study suggests prospective biomarkers that predict response to therapy. The importance of genes involved with genomic stability is highlighted in both development and progression of head and neck squamous cell carcinoma but also recurrence. Potential development of an assay may prove beneficial to clinicians, assisting them to provide alternative care sooner thus lowering morbidity.

Fig. 1

Validation of microarray results utilizing RT-PCR. Values indicate fold-difference of Post-Tx Fails compared to CRs. Light gray microarray result; dark gray RT-PCR result

Fig. 2

Hierarchical clustering based upon 49 genes that are differentially expressed between the Post-Tx Fails and CRs (p ≤ 0.01 and 1.5-fold cutoff). Patients are clustered on the horizontal axis (samples in orange correspond to the Post-Tx Fails; purple CRs)

Fig. 3

Sub-network of genes regulated by E2F3, E2F4, and the E2F functional group. Pathway includes genes differentially expressed between Post-Tx Fails and CRs (ANOVA, p ≤ 0.10 and fold-change ≥1.2). Red upregulated in Post-Tx Fails compared to CRs; blue downregulated. p value and fold-change requirement not met for E2F3 and E2F4