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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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          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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              Human papillomavirus infection and laryngeal cancer risk: a systematic review and meta-analysis.

              A number of molecular epidemiological studies have been conducted to explore the association of human papillomavirus (HPV) infection with laryngeal cancer. However, the findings are heterogeneous. We systematically reviewed studies on HPV infection and laryngeal cancer published up to 15 May 2012 and quantitatively summarized the prevalence of HPV infection and its association with the risk of laryngeal cancer by means of meta-analysis. In total, 55 eligible studies were included. The overall HPV prevalence in laryngeal cancer tissues was 28.0% (95% confidence interval [CI], 23.5%-32.9%). A total of 26.6% laryngeal cancer patients were infected with high-risk HPV types only, and HPV-16 was most frequently observed type, with a prevalence of 19.8% (95% CI, 15.7%-24.6%). The meta-analysis based on 12 eligible case-control studies suggests a strong association between HPV infection and laryngeal squamous cell carcinoma, with a summary odds ratio (OR) of 5.39 (95% CI, 3.25-8.94). Different magnitudes of association were observed for HPV-16 (OR, 6.07; 95% CI, 3.44-10.70) and HPV-18 (OR = 4.16; 95% CI, .87-20.04; P < .01). Stratified analyses were performed with respect to HPV genotypes and characteristics of the study population. HPV infection, especially infection due to the high-risk type HPV-16, was found to be significantly associated with the risk of laryngeal squamous cell carcinoma.
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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
                © 2017

                http://www.springer.com/tdm

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