Abstract 4808: Identification of genes with variants in HPV-associated head and neck squamous cell carcinoma
Authors: Virani Shama , Hall Pelle B. , Zhang Yanxiao , Koneva Lada A. , Virani Alisha , Rentschler Katie M. , Carey Thomas E. , Rozek Laura S. , Sartor Maureen A. 
Published: August 2015

Abstract
Introduction:
Human papilloma virus (HPV)-associated head and neck squamous cell carcinomas have a distinct etiologic mechanism of carcinogenesis compared to non-HPV associated HNSCCs. These tumors are also generally thought to harbor less mutations compared to non-HPV associated HNSCCs. However, recent research suggests that not only do HPV-associated HNSCCs contain mutations, they are distinct from mutations found in non-HPV associated HNSCCs. Identification of these genetic variants is necessary to determine potential prognostic markers or novel insight into the mechanism of HPV-induced carcinogenesis. In this study, we identified genes with variants that are more common in HPV-associated HNSCCs compared to non-HPV associated HNSCCs.
Materials and methods:
Thirty-six primary head and neck SCC (HNSCC) tumor samples were collected between 2011-2013 at University of Michigan hospital, of which 18 were determined to be HPV+ (type16, 18 or 35). Paired-end RNA-Seq libraries were generated using Illumina HiSeq for all samples and aligned to both the human and HPV genome. Variant calling was employed using an established pipeline to identify single nucleotide polymorphisms (SNPs) from RNA-Seq data. Briefly, data was aligned using STAR, followed by indel realignment and base recalibration. Variants were called using HaplotypeCaller and filtered by Fisher Strand values (FS &gt; 30.0) and Qual By Depth values (QD &lt; 2.0). Variants were annotated and filtered by SnpEff and SnpSift to determine genes with nonsynonymous variants by HPV status.
Results:
Out of all samples, nine genes showed nonsynonymous variants in HPV-associated tumors greater than 60% of the time compared to non-HPV associated tumors. These are PTCH1 (associated with eosophageal squamous cell carcinoma), ATRX (involved in chromatin binding), ERCC2 (associated with skin cancers), FOXA1 (transcription factor), CCDC6 (associated with thyroid papillary carcinoma), FNBP1 (involved in lipid binding), and POU5F1 (transcription factor). Seventy-five percent of the samples with nonsynonymous variants in TMPRSS2, a gene shown to be associated with prostate cancer, were HPV-associated tumors. Eighty-two percent of all samples with nonsynonymous variants in FANCD2, a gene involved in maintenance of chromosomal stability, were HPV-associated tumors.
Conclusion:
Although HPV-associated HNSCCs generally harbor fewer mutations than non-HPV associated HNSCCs, our data suggests they do contain variants in cancer-related genes. This is important as these genes may play a role in the mechanism of HPV-induced tumorigenesis subsequent to viral initiation.
Citation Format: Shama Virani, Pelle B. Hall, Yanxiao Zhang, Lada A. Koneva, Alisha Virani, Katie M. Rentschler, Thomas E. Carey, Laura S. Rozek, Maureen A. Sartor. Identification of genes with variants in HPV-associated head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4808. doi:10.1158/1538-7445.AM2015-4808