Detection of Transcriptionally Active High-risk HPV in Patients With Head and Neck Squamous Cell Carcinoma as Visualized by a Novel E6/E7 mRNA In Situ Hybridization Method

Bishop, Justin A.; Xiao, Jun; Wang, Hongwei; Luo, Yuling; Illei, Peter B.; Begum, Shanaz; Taube, Janis M.; Koch, Wayne M.; Westra, William H.

doi:10.1097/pas.0b013e318265fb2b

Cited by 310 publications

(294 citation statements)

References 26 publications

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“…HPV mRNA has been demonstrated in metastases from HPVDNA + tonsillar and base of tongue SCC, while to our knowledge there are only two small studies investigating HPV mRNA in HNCUP, finding HPV mRNA in 10/22 and 2/3 HNCUP respectively (25)(26)(27). Additionally, the latter two studies did not compare HPV mRNA and HPV DNA status.…”

Section: Discussionmentioning

confidence: 84%

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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Section: Discussionmentioning

confidence: 84%

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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“…Thus only integrated and transcriptionally active forms of hrHPV contribute in HPV-related carcinogenesis. HPV E6 and E7 oncoproteins are now established as standard biomarkers for oncogenic activity of hrHPVs, together with more than 70% positivity of p16 protein in tumour cells [4,18,19,23,24]. HPVrelated laryngeal and hypopharyngeal SCC is histologically mostly non-keratinizing SCC, but focally may be also keratinizing.…”

Section: Etiopathogenesis Of Conventional Squamous Cell Carcinoma Sumentioning

confidence: 99%

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What is New in the 2017 WHO Blue Book for Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space

Gale

Poljak

Zidar

2017

Head and Neck Pathol

131

113

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briefly discussed. The most important innovation is brought by the section on precursor lesions, in which a unified twotier classification, consisting of low-and high-grade dysplasia, is introduced. The proposed two-tier system can also be transformed into a three-tier classification for treatment purposes, with a distinction between carcinoma in situ and high-grade dysplasia. The reviewed morphological criteria of the proposed system are based on the amended Ljubljana classification. The section on laryngeal neuroendocrine carcinomas (NEC) represents a considerable improvement in terminology and classification. NEC are divided into well-, moderate-and poorly-differentiated neuroendocrine carcinoma. The latter is additionally divided into small cell NEC and large cell NEC (LCNEC). It is of extreme importance that LCNEC, which was associated in the WHO 2005 edition with atypical carcinoid/moderately differentiated neuroendocrine carcinoma, grade II, has now been transferred into the group of poorly differentiated NEC, grade III, displaying a specific morphology and poorer prognosis.

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“…Third, this study takes advantage of recently developed RNA in situ hybridization probes complementary to E6/E7 mRNA that permit direct visualization of viral transcripts in routinely processed tissues. In formalinfixed and paraffin-embedded oropharyngeal carcinomas, the sensitivity of this method has been shown to exceed that of HPV DNA in situ hybridization [6,[27][28][29].…”

Section: Discussionmentioning

confidence: 99%

“…It is detected in 50-80 % of oropharyngeal cancers where it tracks with the non-keratinizing squamous cell phenotype, but it is not frequently detected in head and neck squamous cell carcinomas arising outside of the oropharynx [4][5][6][7]. In oropharyngeal carcinomas, the detection of HPV is of great clinical significance, as HPV positivity is associated with improved clinical outcomes in ways that modulate therapeutic management [8,9].…”

Section: Introductionmentioning

confidence: 99%

Mucoepidermoid Carcinoma Does Not Harbor Transcriptionally Active High Risk Human Papillomavirus Even in the Absence of the MAML2 Translocation

Bishop

Yonescu

Batista

et al. 2014

Head and Neck Pathol

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High risk human papillomavirus (HPV) is firmly established as an important cause of oropharyngeal carcinoma. Recent studies have also implicated HPV as a cause of mucoepidermoid carcinoma (MEC)-a tumor of salivary gland origin that frequently harbors MAML2 translocations. The purpose of this study was to determine the prevalence of transcriptionally active HPV in a large group of MECs and to determine whether HPV infection and the MAML2 translocation are mutually exclusive events. Break-apart fluorescence in situ hybridization for MAML2 was performed on a tissue microarray containing 92 MECs. HPV testing was performed using RNA in situ hybridization targeting high risk HPV mRNA E6/E7 transcripts. Of the 71 MECs that could be evaluated by FISH, 57 (80 %) harbored the MAML2 rearrangement. HPV was not detected in any of the 57 MECs that contained a MAML2 rearrangement, in any of the 14 MECs that did not contain the rearrangement, or in any of the 21 MECs where MAML2 status was unknown. High risk HPV does not appear to play any significant role in the development of MEC. It neither complements nor replaces MAML2 translocation in the tumorigenesis of MEC.

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Detection of Transcriptionally Active High-risk HPV in Patients With Head and Neck Squamous Cell Carcinoma as Visualized by a Novel E6/E7 mRNA In Situ Hybridization Method

Cited by 310 publications

References 26 publications

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

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

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: What is New in the 2017 WHO Blue Book for Tumours of the Hypopharynx, Larynx, Trachea and Parapharyngeal Space

Mucoepidermoid Carcinoma Does Not Harbor Transcriptionally Active High Risk Human Papillomavirus Even in the Absence of the MAML2 Translocation

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