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.

Differential Effect of Smoking on Gene Expression in Head and Neck Cancer Patients

“…For transcriptomic pattern, altered genes implicated in cell cycle, apoptosis, inflammatory response, DNA replication and repair, or other important transcription factors involved in transcription regulation were revealed [ 47 ]. Gene expression characterization in HPV+ tumors can be used to predict response to therapy, and this information could be used for better tailored therapies [ 62 ]. Our data sustain the idea that HPV-related HNSCC represents a distinct entity, and that current treatment options are not responding to the needs of these patients [ 47 , 61 ], proving the necessity for routine testing of HPV in clinical practice [ 63 ] and at the same time underlining the importance of patient stratification based on smoking status or HPV infection.…”

Hmox1 Upregulation Is a Mutual Marker in Human Tumor Cells Exposed to Physical Plasma-Derived Oxidants

“…This is linked especially to its constitutive upregulation in many types of tumors as well as studies showing that hmox1 downregulation is associated with better outcome. Specifically, among non-responders to chemotherapy in a cohort of head and neck cancer patients, hmox1 was the most upregulated gene that is identified in a transcriptomic microarray study as compared to complete responders [ 56 ].…”

Mining of Self-Organizing Map Gene-Expression Portraits Reveals Prognostic Stratification of HPV-Positive Head and Neck Squamous Cell Carcinoma

“…The cases entered into our study were selected based on the following eligibility criteria: (i) primary lesions of squamous cell carcinoma; (ii) reported HPV status, according to the clinical practice in the reference center; (iii) MIAME (Minimum Information about a Microarray Experiment) [35] complaint data with the availability of raw data deposited on publicly accessible repositories and full gene annotation (Gene Bank accession or EntrezID). After literature revision, there were 11 datasets [12,36,37,38,39,40,41,42,43,44,45]. See Table S1 (Supplementary Materials) for details regarding the datasets including the accession numbers and methods of HPV detection.…”