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    العلاقة: Pinatti, Lisa M.; Sinha, Hana N.; Brummel, Collin V.; Goudsmit, Christine M.; Geddes, Timothy J.; Wilson, George D.; Akervall, Jan A.; Brenner, Chad J.; Walline, Heather M.; Carey, Thomas E. (2021). "Association of human papillomavirus integration with better patient outcomes in oropharyngeal squamous cell carcinoma." Head & Neck 43(2): 544-557.; https://hdl.handle.net/2027.42/166276Test; https://dx.doi.org/10.7302/199Test; Head & Neck; Wittekindt C, Wagner S, Bushnak A, et al. Increasing incidence rates of oropharyngeal squamous cell carcinoma in germany and significance of disease burden attributed to human papillomavirus. Cancer Prev Res (Phila). 2019; 12 ( 6 ): 375 ‐ 382.; Olthof NC, Speel EJ, Kolligs J, et al. Comprehensive analysis of HPV16 integration in OSCC reveals no significant impact of physical status on viral oncogene and virally disrupted human gene expression. Plos One. 2014; 9 ( 2 ): e88718.; Ibragimova M, Tsyganov M, Shpileva O, et al. HPV status and its genomic integration affect survival of patients with cervical cancer. Neoplasma. 2018; 65 ( 3 ): 441 ‐ 448.; Kiseleva VI, Mkrtchyan LS, Ivanov SA, et al. The presence of human papillomavirus DNA integration is associated with poor clinical results in patients with third‐stage cervical cancer. Bull Exp Biol Med. 2019; 168 ( 1 ): 87 ‐ 91.; Shin HJ, Joo J, Yoon JH, Yoo CW, Kim JY. Physical status of human papillomavirus integration in cervical cancer is associated with treatment outcome of the patients treated with radiotherapy. Plos One. 2014; 9 ( 1 ): e78995.; Anayannis NV, Schlecht NF, Ben‐Dayan M, et al. Association of an intact E2 gene with higher HPV viral load, higher viral oncogene expression, and improved clinical outcome in HPV16 positive head and neck squamous cell carcinoma. Plos One. 2018; 13 ( 2 ): e0191581.; Nulton TJ, Kim NK, DiNardo LJ, Morgan IM, Windle B. Patients with integrated HPV16 in head and neck cancer show poor survival. Oral Oncol. 2018; 80: 52 ‐ 55.; Lim MY, Dahlstrom KR, Sturgis EM, Li G. Human papillomavirus integration pattern and demographic, clinical, and survival characteristics of patients with oropharyngeal squamous cell carcinoma. Head Neck. 2016; 38 ( 8 ): 1139 ‐ 1144.; Vojtechova Z, Sabol I, Salakova M, et al. Analysis of the integration of human papillomaviruses in head and neck tumours in relation to patients’ prognosis. Int J Cancer. 2016; 138 ( 2 ): 386 ‐ 395.; Koneva LA, Zhang Y, Virani S, et al. HPV integration in HNSCC correlates with survival outcomes, immune response signatures, and candidate drivers. Mol Cancer Res. 2017; 16 ( 1 ): 90 – 102.; Walline HM, Komarck CM, McHugh JB, et al. Genomic integration of high‐risk HPV alters gene expression in oropharyngeal squamous cell carcinoma. Mol Cancer Res. 2016; 14 ( 10 ): 941 ‐ 952.; Walline HM, Komarck CM, McHugh JB, et al. 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Identification of reliable biomarkers of human papillomavirus 16 methylation in cervical lesions based on integration status using high‐resolution melting analysis. Clin Epigenetics. 2018; 10: 10.; Schmitz M, Driesch C, Jansen L, Runnebaum IB, Durst M. Non‐random integration of the HPV genome in cervical cancer. PLoS One. 2012; 7 ( 6 ): e39632.; Pinatti LM, Walline HM, Carey TE, Klussman JP, Huebbers CU. Viral integration analysis reveals likely common clonal origin of bilateral HPV16‐positive, p16‐positive tonsil tumors. Arch Clin Med Case Rep. 2020; 4: 680 ‐ 696.; Chen J, Li S, Zhou S, et al. Kinesin superfamily protein expression and its association with progression and prognosis in hepatocellular carcinoma. J Cancer Res Ther. 2017; 13 ( 4 ): 651 ‐ 659.; Sun ZG, Pan F, Shao JB, Yan QQ, Lu L, Zhang N. Kinesin superfamily protein 21B acts as an oncogene in non‐small cell lung cancer. Cancer Cell Int. 2020; 20: 233.; Zhao HQ, Dong BL, Zhang M, et al. Increased KIF21B expression is a potential prognostic biomarker in hepatocellular carcinoma. World J Gastrointest Oncol. 2020; 12 ( 3 ): 276 ‐ 288.; Reuschenbach M, Huebbers CU, Prigge ES, et al. Methylation status of HPV16 E2‐binding sites classifies subtypes of HPV‐associated oropharyngeal cancers. Cancer Am Cancer Soc. 2015; 121 ( 12 ): 1966 ‐ 1976.; von Knebel Doeberitz M, Prigge ES. Role of DNA methylation in HPV associated lesions. Papillomavirus Res. 2019; 7: 180 ‐ 183.; Wallace NA, Khanal S, Robinson KL, Wendel SO, Messer JJ, Galloway DA. High‐risk alphapapillomavirus oncogenes impair the homologous recombination pathway. J Virol. 2017; 91 ( 20 ):e01084‐17. https://doi.org/10.1128/JVI.01084-17Test.; Oguejiofor K, Hall J, Slater C, et al. Stromal infiltration of CD8 T cells is associated with improved clinical outcome in HPV‐positive oropharyngeal squamous carcinoma. Br J Cancer. 2015; 113 ( 6 ): 886 ‐ 893.; Mahal BA, Catalano PJ, Haddad RI, et al. Incidence and demographic burden of HPV‐associated oropharyngeal head and neck cancers in the United States. Cancer Epidemiol Biomarkers Prev. 2019; 28 ( 10 ): 1660 ‐ 1667.; Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000; 92 ( 9 ): 709 ‐ 720.; Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus‐positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008; 100 ( 4 ): 261 ‐ 269.; Licitra L, Perrone F, Bossi P, et al. High‐risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J Clin Oncol. 2006; 24 ( 36 ): 5630 ‐ 5636.; Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010; 363 ( 1 ): 24 ‐ 35.; Bodelon C, Untereiner ME, Machiela MJ, Vinokurova S, Wentzensen N. Genomic characterization of viral integration sites in HPV‐related cancers. Int J Cancer. 2016; 139 ( 9 ): 2001 ‐ 2011.; Gao G, Wang J, Kasperbauer JL, et al. Whole genome sequencing reveals complexity in both HPV sequences present and HPV integrations in HPV‐positive oropharyngeal squamous cell carcinomas. BMC Cancer. 2019; 19 ( 1 ): 352.; Holmes A, Lameiras S, Jeannot E, et al. Mechanistic signatures of HPV insertions in cervical carcinomas. NPJ Genom Med. 2016; 1: 16004.; Kalantari M, Villa LL, Calleja‐Macias IE, Bernard HU. Human papillomavirus‐16 and ‐18 in penile carcinomas: DNA methylation, chromosomal recombination and genomic variation. Int J Cancer. 2008; 123 ( 8 ): 1832 ‐ 1840.; Morel A, Neuzillet C, Wack M, et al. Mechanistic signatures of human papillomavirus insertions in anal squamous cell carcinomas. Cancers (Basel). 2019; 11 ( 12 ): 1846. https://doi.org/10.3390/cancers11121846Test.; Nulton TJ, Olex AL, Dozmorov M, Morgan IM, Windle B. Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma. Oncotarget. 2017; 8 ( 11 ): 17684 ‐ 17699.; Parfenov M, Pedamallu CS, Gehlenborg N, et al. Characterization of HPV and host genome interactions in primary head and neck cancers. Proc Natl Acad Sci U S A. 2014; 111 ( 43 ): 15544 ‐ 15549.; Hu Z, Zhu D, Wang W, et al. Genome‐wide profiling of HPV integration in cervical cancer identifies clustered genomic hot spots and a potential microhomology‐mediated integration mechanism. Nat Genet. 2015; 47 ( 2 ): 158 ‐ 163.; McBride AA, Warburton A. The role of integration in oncogenic progression of HPV‐associated cancers. PLoS Pathog. 2017; 13 ( 4 ): e1006211.; McBride AA. The papillomavirus E2 proteins. Virology. 2013; 445 ( 1–2 ): 57 ‐ 79.; Zhang Y, Koneva LA, Virani S, et al. Subtypes of HPV‐positive head and neck cancers are associated with HPV characteristics, copy number alterations, PIK3CA mutation, and pathway signatures. Clin Cancer Res. 2016; 22 ( 18 ): 4735 ‐ 4745.; Qin T, Koneva LA, Liu Y, et al. Significant association between host transcriptome‐derived HPV oncogene E6* influence score and carcinogenic pathways, tumor size, and survival in head and neck cancer. Head Neck. 2020; 42 ( 9 ): 2375 ‐ 2389.; Jeon S, Lambert PF. Integration of human papillomavirus type 16 DNA into the human genome leads to increased stability of E6 and E7 mRNAs: implications for cervical carcinogenesis. Proc Natl Acad Sci USA. 1995; 92 ( 5 ): 1654 ‐ 1658.; Akagi K, Li J, Broutian TR, et al. Genome‐wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability. Genome Res. 2014; 24 ( 2 ): 185 ‐ 199.; Walline HM, Goudsmit CM, McHugh JB, et al. Integration of high‐risk human papillomavirus into cellular cancer‐related genes in head and neck cancer cell lines. Head Neck. 2017; 39 ( 5 ): 840 ‐ 852.

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