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      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

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      Head and Neck Pathology
      Springer Nature

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          Abstract

          <p class="first" id="d3944506e142">Chapter 3 “Tumours of the hypopharynx, larynx, trachea, and parapharyngeal space” of the World Health Organization (WHO) Blue Book 2017 “Classification of Head and Neck Tumours” shows a shortened list of entities, especially due to reducing the number of benign and malignant soft tissue tumours, malignant melanoma and some others, which are transferred to more frequently affected regions of the head and neck. The basic concept of the new edition is to assimilate all advances concerning the discussed tumours in a shorter framework, appropriate for daily work. The main emphasis is on the most frequent lesions and tumors originating from the covering squamous epithelium. Laryngeal and hypopharyngeal conventional squamous cell carcinoma (CSCC), its variants and precursor lesions, occupy a major part of the chapter. New data on etiopathogenesis, with the focus on human papillomavirus (HPV) infection, are discussed in relation to the entities of the squamous epithelium. Although only a small fraction of these lesions are HPV-related, further studies are required for evaluation of the potential prognostic and therapeutic benefit of mRNA HPV determination. In contrast to earlier data, laryngeal and hypopharyngeal verrucous SCC, spindle cell SCC and basaloid SCC are not anymore considered as HPV-related tumours. New data on the pathogenesis of spindle cell SCC exhibiting divergent differentiation by epithelial—mesenchymal transition, are also briefly discussed. The most important innovation is brought by the section on precursor lesions, in which a unified two-tier 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. </p>

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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.

          Evidence for transcriptional activation of the viral oncoproteins E6 and E7 is regarded as the gold standard for the presence of clinically relevant human papillomavirus (HPV), but detection of E6/E7 mRNA requires RNA extraction and polymerase chain reaction amplification-a challenging technique that is restricted to the research laboratory. The development of RNA in situ hybridization (ISH) probes complementary to E6/E7 mRNA permits direct visualization of viral transcripts in routinely processed tissues and has opened the door for accurate HPV detection in the clinical care setting. Tissue microarrays containing 282 head and neck squamous cell carcinomas from various anatomic subsites were tested for the presence of HPV using p16 immunohistochemistry, HPV DNA ISH, and an RNA ISH assay (RNAscope) targeting high-risk HPV E6/E7 mRNA transcripts. The E6/E7 mRNA assay was also used to test an additional 25 oropharyngeal carcinomas in which the HPV status as recorded in the surgical pathology reports was equivocal due to conflicting detection results (ie, p16 positive, DNA ISH negative). By the E6/E7 mRNA method, HPV was detected in 49 of 282 (17%) HNSCCs including 43 of 77 (56%) carcinomas from the oropharynx, 2 of 3 (67%) metastatic HNSCCs of an unknown primary site, 2 of 7 (29%) carcinomas from the sinonasal tract, and 2 of 195 (1%) carcinomas from other head and neck sites. p16 expression was strongly associated with the presence of HPV E6/E7 mRNA: 46 of 49 HPV-positive tumors exhibited p16 expression, whereas only 22 of 233 HPV-negative tumors were p16 positive (94% vs. 9%, P<0.0001). There was also a high rate of concordance (99%) between the E6/E7 mRNA method and HPV DNA ISH. For the selected group of discordant HNSCCs (p16/HPV DNA), the presence of E6/E7 transcripts was detected in 21 of 25 (84%) cases. The E6/E7 mRNA method confirmed the presence of transcriptionally active HPV-related HNSCC that has a strong predilection for the oropharynx and is strongly associated with high levels of p16 expression. Testing for HPV E6/E7 transcripts by RNA ISH is ideal because it confirms the presence of integrated and transcriptionally active virus, permits visualization of viral transcripts in tissues, and is technically feasible for routine testing in the clinical laboratory.
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            Human papillomavirus in non-oropharyngeal head and neck cancers: a systematic literature review.

            Perhaps one of the most important developments in head and neck oncology of the past decade is the demonstration that patients with human papillomavirus (HPV)-mediated oropharyngeal cancers have significantly improved outcomes, compared to HPV-negative counterpart patients. This has become the basis for clinical trials investigating the impact on "treatment deintensification" for patients with HPV-mediated oropharyngeal cancers. Unfortunately, the significance of HPV in non-oropharyngeal head and neck cancers is much less certain. Our goal is to systematically review the published data regarding the role HPV in carcinomas of the oral cavity, larynx, sinonasal tract and nasopharynx with respect to HPV detection frequency, viral activity, and association with outcome. We also present preliminary data on HPV16/18 transcriptional status in oral cavity carcinomas, as well as salivary gland neoplasia, as determined by nested reverse transcription PCR for HPV E6/E7 RNA. The weighted prevalence (WP) of HPV DNA detection in 4,195 oral cavity cancer patients is 20.2 %, (95 % CI 16.0 %, 25.2 %). HPV16 is the most common type detected. Importantly, no data currently demonstrates a significant association between the presence of HPV DNA and improved outcome. The WP of HPV DNA in 1,712 laryngeal cancer patients is 23.6 %, (95 % CI 18.7 %, 29.3 %). Similarly, no association has yet been demonstrated between HPV DNA status and outcome. The WP of HPV DNA detection in 120 sinonasal cancer patients is 29.6 % (95 % CI 17.8 %, 44.9 %), and in 154 nasopharyngeal carcinoma patients is 31.1 %, (95 % CI 20.3 %, 44.5 %). Recent preliminary data also suggests an association between HPV and certain salivary gland neoplasms. The clinical significance of these findings is unclear. The published data strongly support the need for studies on patients with oral and laryngeal carcinomas that will be powered to find any differences in clinical outcome with respect to HR-HPV and p16 overexpression.
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              The epidemiology of the human papillomavirus related to oropharyngeal head and neck cancer.

              To summarize the epidemiology of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OSCC).
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                Author and article information

                Journal
                Head and Neck Pathology
                Head and Neck Pathol
                Springer Nature
                1936-055X
                1936-0568
                March 2017
                February 28 2017
                : 11
                : 1
                : 23-32
                Article
                10.1007/s12105-017-0788-z
                5340729
                28247231
                4fdcd54b-93ef-4fc9-aa2e-b5b0ec069a3f
                © 2017

                http://www.springer.com/tdm

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