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Subtypes of HPV-Positive Head and Neck Cancers Are Associated with HPV Characteristics, Copy Number Alterations, PIK3CA Mutation, and Pathway Signatures.


ABSTRACT: There is substantial heterogeneity within human papillomavirus (HPV)-associated head and neck cancer (HNC) tumors that predispose them to different outcomes; however, the molecular heterogeneity in this subgroup is poorly characterized due to various historical reasons.We performed unsupervised gene expression clustering on deeply annotated (transcriptome and genome) HPV(+) HNC samples from two cohorts (84 total primary tumors), including 18 HPV(-) HNC samples, to discover subtypes and characterize the differences between subgroups in terms of their HPV characteristics, pathway activity, whole-genome somatic copy number alterations, and mutation frequencies.We identified two distinct HPV(+) subtypes (namely HPV-KRT and HPV-IMU). HPV-KRT is characterized by elevated expression of genes in keratinocyte differentiation and oxidation-reduction process, whereas HPV-IMU has strong immune response and mesenchymal differentiation. The differences in expression are likely connected to the differences in HPV characteristics and genomic changes. HPV-KRT has more genic viral integration, lower E2/E4/E5 expression levels, and higher ratio of spliced to full-length HPV oncogene E6 than HPV-IMU; the subgroups also show differences in copy number alterations and mutations, in particular the loss of chr16q in HPV-IMU and gain of chr3q and PIK3CA mutation in HPV-KRT.Our characterization of two subtypes of HPV(+) HNC tumors provides valuable molecular level information that point to two main carcinogenic paths. Together, these results shed light on stratifications of the HPV(+) HNCs and will help to guide personalized care for HPV(+) HNC patients. Clin Cancer Res; 22(18); 4735-45. ©2016 AACR.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC5026546 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Subtypes of HPV-Positive Head and Neck Cancers Are Associated with HPV Characteristics, Copy Number Alterations, PIK3CA Mutation, and Pathway Signatures.

Zhang Yanxiao Y   Koneva Lada A LA   Virani Shama S   Arthur Anna E AE   Virani Alisha A   Hall Pelle B PB   Warden Charles D CD   Carey Thomas E TE   Chepeha Douglas B DB   Prince Mark E ME   McHugh Jonathan B JB   Wolf Gregory T GT   Rozek Laura S LS   Sartor Maureen A MA  

Clinical cancer research : an official journal of the American Association for Cancer Research 20160418 18


<h4>Purpose</h4>There is substantial heterogeneity within human papillomavirus (HPV)-associated head and neck cancer (HNC) tumors that predispose them to different outcomes; however, the molecular heterogeneity in this subgroup is poorly characterized due to various historical reasons.<h4>Experimental design</h4>We performed unsupervised gene expression clustering on deeply annotated (transcriptome and genome) HPV(+) HNC samples from two cohorts (84 total primary tumors), including 18 HPV(-) HNC  ...[more]

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