Studies on human papillomavirus (HPV) 16 E2, E5 and E7 mRNA in HPV-positive tonsillar and base of tongue cancer in relation to clinical outcome and immunological parameters

Ramqvist, Torbjörn; Mints, Michael; Tertipis, Nikolaos; Näsman, Anders; Romanitan, Mircea; Dalianis, Tina

doi:10.1016/j.oraloncology.2015.09.007

Cited by 44 publications

(56 citation statements)

References 185 publications

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“…Such a simple characterization could be used to definitively determine whether there is a worse outcome in patients with HPV+ HNC that have integrated HPV genomes versus those with HNC with episomal HPV, which would include episomal HPV-human hybrid DNA. A recent analysis of HPV positive tonsillar and base of tongue cancers showed expression of E2 in 64% of tumors aligning with our data [39]. …”

Section: Discussionsupporting

confidence: 92%

Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma

et al. 2017

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Human papillomavirus (HPV) DNA is detected in up to 80% of oropharyngeal carcinomas (OPC) and this HPV positive disease has reached epidemic proportions. To increase our understanding of the disease, we investigated the status of the HPV16 genome in HPV-positive head and neck cancers (HNC). Raw RNA-Seq and Whole Genome Sequence data from The Cancer Genome Atlas HNC samples were analyzed to gain a full understanding of the HPV genome status for these tumors. Several remarkable and novel observations were made following this analysis. Firstly, there are three main HPV genome states in these tumors that are split relatively evenly: An episomal only state, an integrated state, and a state in which the viral genome exists as a hybrid episome with human DNA. Secondly, none of the tumors expressed high levels of E6; E6*I is the dominant variant expressed in all tumors. The most striking conclusion from this study is that around three quarters of HPV16 positive HNC contain episomal versions of the viral genome that are likely replicating in an E1-E2 dependent manner. The clinical and therapeutic implications of these observations are discussed.

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Section: Discussionsupporting

confidence: 92%

Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma

et al. 2017

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“…In cervical cancer, it was found that patients who only had integrated HPV expression had a trend towards worse disease free survival compared to patients with both integrated and episomal HPV forms (40). Studies on HNCs showed worse recurrence-free survival for HPV(+) tumors with low levels of E2 (41) and E5 (42), markers for integrated HPV. HPV-IMU has much higher levels of BCL2 expression than HPV-KRT, which has been reported to correlate with more favorable outcome in HNCs (43,44).…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Koneva

Virani

et al. 2016

Clinical Cancer Research

120

170

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Structured Abstract Purpose 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. Experimental Design 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. Results 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. Conclusion 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.

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“…Random hexamer primers were used. A PCR was run to amplify HPV16 E2, E5, E6*I, E6*II and E7 mRNA, and the housekeeping gene U1A to control for amplifiable RNA, and β-globin to verify that no DNA remained, as previously described for E2, E5 and E7 (19). The following primers were used for amplification of E6*I and E6*II cDNA: HPV16E6_194.F bp194-214 5'-GTGTACTGCAAGCAA CAGTTA-3', HPV16E6_565.R bp 565-545 5'-GC ATGATTACAGCTGG GTTTC-3', HPV16E6_445.R bp 445-425 5'-TTCTTCAGGACA CAGTGGCTT-3'.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, the joint cohort was used to analyse the influence on survival of cluster of differentiation 8-positive (CD8 + ) tumourinfiltrating lymphocytes (TILs) and HLA class I expression, two prognostic biomarkers in addition to HPV status in tonsillar and base of tongue SCC (3,(18)(19)(20).…”

mentioning

confidence: 99%

Validation of Human Papillomavirus as a Favourable Prognostic Marker and Analysis of CD8+ Tumour-infiltrating Lymphocytes and Other Biomarkers in Cancer of Unknown Primary in the Head and Neck Region

Sivars¹,

Landin²,

Grün³

et al. 2017

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Abstract. Background: Human papillomavirus (HPV) is a favourable prognostic factor in oropharyngeal cancer. Moreover, we and others reported that HPV-positive cancer of unknown primary in the head and neck region (HNCUP) has better outcome than HPVHead and neck squamous cell carcinoma (HNSCC), including cancer of the pharynx, larynx, oral cavity, nose and nasal sinuses, often presents as a lump in the neck, and the specific site of the primary tumour is in general revealed after subsequent diagnostic procedures. However, in 2-9% of the cases the primary tumour is not found and the condition is denoted as cancer of unknown primary in the head and neck region (HNCUP) (1). Treatment of the latter has traditionally comprised of neck dissection followed by postoperative oncological treatment, i.e. radiotherapy, at times with the addition of platinum-based chemotherapy or cetuximab, while today in some cases only oncological treatment is given (2).Human papillomavirus (HPV)-associated oropharyngeal SCC is a HNSCC subset dominated by tonsillar and base of tongue SCC (3, 4). HPV-positive tonsillar and base of tongue SCC have increased in incidence in the past decades in the developed world and have better clinical outcomes than HNSCC in general [~80% vs. 40% 5-year overall survival (OS)] (5-8). HPV is frequently found in HNCUP and such cases likely have an HPV-positive oropharyngeal SCC origin, which gives reasons for steering diagnostic procedures as well as radiotherapy towards the oropharynx (9-11).Treatment de-escalation may be attainable in patients with HPV-positive HNCUP, similar to that discussed for patients with HPV-positive oropharyngeal SCC (12). Still, before HPV status of HNCUP can be used to guide treatment, more knowledge on the biology and clinical behaviour of the 665 Τhis article is freely accessible online.

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Studies on human papillomavirus (HPV) 16 E2, E5 and E7 mRNA in HPV-positive tonsillar and base of tongue cancer in relation to clinical outcome and immunological parameters

Cited by 44 publications

References 185 publications

Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma

Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma

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

Validation of Human Papillomavirus as a Favourable Prognostic Marker and Analysis of CD8+ Tumour-infiltrating Lymphocytes and Other Biomarkers in Cancer of Unknown Primary in the Head and Neck Region

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