Top

Published in:

01-07-2019 | Original Article

Clinical and Molecular Characterization of Surgically Treated Oropharynx Squamous Cell Carcinoma Samples

Authors: Ana Carolina de Carvalho, Matias Eliseo Melendez, Cristina da Silva Sabato, Edenir Inez Palmero, Lidia Maria Rebolho Batista Arantes, Cristovam Scapulatempo Neto, André Lopes Carvalho

Published in: Pathology & Oncology Research | Issue 3/2019

Abstract

A better understanding of the clinical and molecular features of oropharyngeal squamous cell carcinomas (OPSCC) may help in the development of strategies for a better patient management, improving survival rates. This retrospective study conducted a clinical and molecular characterization of surgically treated OPSCC samples. Paraffin-embedded samples from a series of cases were screened for high-risk (HR) human papillomavirus (HPV) infection, methylation of a 5-gene panel, p53 expression, and TP53 mutation. The study was conducted at Barretos Cancer Hospital. Twenty-five surgically treated OPSCC with available tissue were included in the study. Samples were classified according to HPV status and molecular features and some of these characteristics were associated to clinical data. Twenty percent of the cases were HR-HPV positive and 62.5% presented TP53 mutations. DAPK hypermethylation was associated with HPV status (p = 0.023), while methylated CCNA1 was inversely related to TP53 mutations in primary tumors (p = 0.042) and associated with a better disease-free survival (22.3% vs. 100.0%; p = 0.028) and overall survival (8.0% vs. 100.0%; p = 0.012). The results show differences regarding molecular and clinical characteristics in the oropharynx cases identified that should be validated in more cases to confirm whether these differences are able to classify patients according to outcome and help in a more thorough patient management.

Available only for authorised users

Gillison ML, D'Souza G, Westra W, Sugar E, Xiao W, Begum S, Viscidi R (2008) Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst 100(6):407–420. https://doi.org/10.1093/jnci/djn025 CrossRefPubMed

Marur S, D'Souza G, Westra WH, Forastiere AA (2010) HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol 11(8):781–789. https://doi.org/10.1016/S1470-2045(10)70017-6 CrossRefPubMedPubMedCentral

Marklund L, Hammarstedt L (2011) Impact of HPV in oropharyngeal Cancer. J Oncol 2011:509036. https://doi.org/10.1155/2011/509036 CrossRefPubMed

Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C (2015) Epidemiology of human papillomavirus-positive head and neck squamous cell carcinoma. J Clin Oncol Off J Am Soc Clin Oncol 33(29):3235–3242. https://doi.org/10.1200/JCO.2015.61.6995 CrossRef

Kreimer AR, Clifford GM, Boyle P, Franceschi S (2005) Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev 14(2):467–475. https://doi.org/10.1158/1055-9965.EPI-04-0551 CrossRefPubMed

Zhen W, Karnell LH, Hoffman HT, Funk GF, Buatti JM, Menck HR (2004) The National Cancer Data Base report on squamous cell carcinoma of the base of tongue. Head Neck 26(8):660–674. https://doi.org/10.1002/hed.20064 CrossRefPubMed

Lybak S, Ljokjel B, Haave H, Karlsdottir A, Vintermyr OK, Aarstad HJ (2017) Primary surgery results in no survival benefit compared to primary radiation for oropharyngeal cancer patients stratified by high-risk human papilloma virus status. Eur Arch Otorhinolaryngol 274(1):477–487. https://doi.org/10.1007/s00405-016-4203-2 CrossRefPubMed

Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol Off J Am Soc Clin Oncol 29(32):4294–4301. https://doi.org/10.1200/JCO.2011.36.4596 CrossRef

Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer DE, Shah KV, Sidransky D (2000) Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 92(9):709–720CrossRefPubMed

10.

Mellin H, Friesland S, Lewensohn R, Dalianis T, Munck-Wikland E (2000) Human papillomavirus (HPV) DNA in tonsillar cancer: clinical correlates, risk of relapse, and survival. Int J Cancer 89(3):300–304CrossRefPubMed

11.

Hafkamp HC, Manni JJ, Haesevoets A, Voogd AC, Schepers M, Bot FJ, Hopman AH, Ramaekers FC, Speel EJ (2008) Marked differences in survival rate between smokers and nonsmokers with HPV 16-associated tonsillar carcinomas. Int J Cancer 122(12):2656–2664. https://doi.org/10.1002/ijc.23458 CrossRefPubMed

12.

Goldenberg D, Begum S, Westra WH, Khan Z, Sciubba J, Pai SI, Califano JA, Tufano RP, Koch WM (2008) Cystic lymph node metastasis in patients with head and neck cancer: an HPV-associated phenomenon. Head Neck 30(7):898–903. https://doi.org/10.1002/hed.20796 CrossRefPubMed

13.

Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363(1):24–35. https://doi.org/10.1056/NEJMoa0912217 CrossRefPubMedPubMedCentral

14.

Gillison ML, Zhang Q, Jordan R, Xiao W, Westra WH, Trotti A, Spencer S, Harris J, Chung CH, Ang KK (2012) Tobacco smoking and increased risk of death and progression for patients with p16-positive and p16-negative oropharyngeal cancer. J Clin Oncol Off J Am Soc Clin Oncol 30(17):2102–2111. https://doi.org/10.1200/JCO.2011.38.4099 CrossRef

15.

Deschler DG, Richmon JD, Khariwala SS, Ferris RL, Wang MB (2014) The “new” head and neck cancer patient-young, nonsmoker, nondrinker, and HPV positive: evaluation. Otolaryngol Head Neck Surg 151(3):375–380. https://doi.org/10.1177/0194599814538605 CrossRefPubMedPubMedCentral

16.

Dansky Ullmann C, Harlan LC, Shavers VL, Stevens JL (2012) A population-based study of therapy and survival for patients with head and neck cancer treated in the community. Cancer 118(18):4452–4461. https://doi.org/10.1002/cncr.27419 CrossRefPubMed

17.

Huang SH, Xu W, Waldron J, Siu L, Shen X, Tong L, Ringash J, Bayley A, Kim J, Hope A, Cho J, Giuliani M, Hansen A, Irish J, Gilbert R, Gullane P, Perez-Ordonez B, Weinreb I, Liu FF, O'Sullivan B (2015) Refining American Joint Committee on Cancer/Union for International Cancer Control TNM stage and prognostic groups for human papillomavirus-related oropharyngeal carcinomas. J Clin Oncol 33(8):836–845. https://doi.org/10.1200/JCO.2014.58.6412 CrossRefPubMed

18.

Lindel K, Beer KT, Laissue J, Greiner RH, Aebersold DM (2001) Human papillomavirus positive squamous cell carcinoma of the oropharynx: a radiosensitive subgroup of head and neck carcinoma. Cancer 92(4):805–813CrossRefPubMed

19.

Dahlstrand HM, Dalianis T (2005) Presence and influence of human papillomaviruses (HPV) in tonsillar cancer. Adv Cancer Res 93:59–89. https://doi.org/10.1016/S0065-230X(05)93002-9 CrossRefPubMed

20.

Shimura E, Hama T, Suda T, Ikegami M, Urashima M, Kojima H (2017) The presence of HPV DNA in neck lymph node metastasis correlates with improved overall survival of patients with oropharyngeal cancer undergoing surgical treatment. Oncology 92(2):87–93. https://doi.org/10.1159/000452420 CrossRefPubMed

21.

Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Brandsma J, Sasaki C, Joe J, Camp RL, Rimm DL, Psyrri A (2006) Molecular classification identifies a subset of human papillomavirus--associated oropharyngeal cancers with favorable prognosis. J Clin Oncol Off J Am Soc Clin Oncol 24(5):736–747. https://doi.org/10.1200/JCO.2004.00.3335 CrossRef

22.

Begum S, Gillison ML, Ansari-Lari MA, Shah K, Westra WH (2003) Detection of human papillomavirus in cervical lymph nodes: a highly effective strategy for localizing site of tumor origin. Clin Cancer Res 9(17):6469–6475PubMed

23.

Singhi AD, Westra WH (2010) Comparison of human papillomavirus in situ hybridization and p16 immunohistochemistry in the detection of human papillomavirus-associated head and neck cancer based on a prospective clinical experience. Cancer 116(9):2166–2173. https://doi.org/10.1002/cncr.25033 CrossRefPubMed

24.

Keswani RN, Noffsinger A, Waxman I, Bissonnette M (2006) Clinical use of p53 in Barrett’s esophagus. Cancer Epidemiol Biomarkers Prev 15(7):1243–1249. https://doi.org/10.1158/1055-9965.EPI-06-0010 CrossRefPubMed

25.

Rettori MM, de Carvalho AC, Bomfim Longo AL, de Oliveira CZ, Kowalski LP, Carvalho AL, Vettore AL (2013) Prognostic significance of TIMP3 hypermethylation in post-treatment salivary rinse from head and neck squamous cell carcinoma patients. Carcinogenesis 34(1):20–27. https://doi.org/10.1093/carcin/bgs311 CrossRefPubMed

26.

Brabender J, Usadel H, Danenberg KD, Metzger R, Schneider PM, Lord RV, Wickramasinghe K, Lum CE, Park J, Salonga D, Singer J, Sidransky D, Holscher AH, Meltzer SJ, Danenberg PV (2001) Adenomatous polyposis coli gene promoter hypermethylation in non-small cell lung cancer is associated with survival. Oncogene 20(27):3528–3532. https://doi.org/10.1038/sj.onc.1204455 CrossRefPubMed

27.

Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, Rosenberg PS, Bray F, Gillison ML (2013) Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol Off J Am Soc Clin Oncol 31(36):4550–4559. https://doi.org/10.1200/JCO.2013.50.3870 CrossRef

28.

Howard J, Masterson L, Dwivedi RC, Riffat F, Benson R, Jefferies S, Jani P, Tysome JR, Nutting C (2016) Minimally invasive surgery versus radiotherapy/chemoradiotherapy for small-volume primary oropharyngeal carcinoma. Cochrane Database Syst Rev 12:CD010963. https://doi.org/10.1002/14651858.CD010963.pub2 CrossRefPubMed

29.

Parsons JT, Mendenhall WM, Stringer SP, Amdur RJ, Hinerman RW, Villaret DB, Moore-Higgs GJ, Greene BD, Speer TW, Cassisi NJ, Million RR (2002) Squamous cell carcinoma of the oropharynx: surgery, radiation therapy, or both. Cancer 94(11):2967–2980. https://doi.org/10.1002/cncr.10567 CrossRefPubMed

30.

Blanchard P, Hill C, Guihenneuc-Jouyaux C, Baey C, Bourhis J, Pignon JP (2011) Mixed treatment comparison meta-analysis of altered fractionated radiotherapy and chemotherapy in head and neck cancer. J Clin Epidemiol 64(9):985–992. https://doi.org/10.1016/j.jclinepi.2010.10.016 CrossRefPubMed

31.

Lee J, Chang JS, Kwon HJ, Kim SH, Shin SJ, Keum KC (2016) Impact of p16 expression in oropharyngeal cancer in the postoperative setting: the necessity of re-evaluating traditional risk stratification. Jpn J Clin Oncol 46(10):911–918. https://doi.org/10.1093/jjco/hyw099 CrossRefPubMed

32.

Dahlstrom KR, Calzada G, Hanby JD, Garden AS, Glisson BS, Li G, Roberts DB, Weber RS, Sturgis EM (2013) An evolution in demographics, treatment, and outcomes of oropharyngeal cancer at a major cancer center: a staging system in need of repair. Cancer 119(1):81–89. https://doi.org/10.1002/cncr.27727 CrossRefPubMed

33.

D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, Westra WH, Gillison ML (2007) Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med 356(19):1944–1956. https://doi.org/10.1056/NEJMoa065497 CrossRefPubMed

34.

O'Sullivan B, Huang SH, Siu LL, Waldron J, Zhao H, Perez-Ordonez B, Weinreb I, Kim J, Ringash J, Bayley A, Dawson LA, Hope A, Cho J, Irish J, Gilbert R, Gullane P, Hui A, Liu FF, Chen E, Xu W (2013) Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis. J Clin Oncol Off J Am Soc Clin Oncol 31(5):543–550. https://doi.org/10.1200/JCO.2012.44.0164 CrossRef

35.

Rischin D, Young RJ, Fisher R, Fox SB, Le QT, Peters LJ, Solomon B, Choi J, O'Sullivan B, Kenny LM, McArthur GA (2010) Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol Off J Am Soc Clin Oncol 28(27):4142–4148. https://doi.org/10.1200/JCO.2010.29.2904 CrossRef

36.

Huang SH, Perez-Ordonez B, Weinreb I, Hope A, Massey C, Waldron JN, Kim J, Bayley AJ, Cummings B, Cho BC, Ringash J, Dawson LA, Siu LL, Chen E, Irish J, Gullane P, Hui A, Liu FF, Shen X, Xu W, O'Sullivan B (2013) Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer. Oral Oncol 49(1):79–85. https://doi.org/10.1016/j.oraloncology.2012.07.015 CrossRefPubMed

37.

McIlwain WR, Sood AJ, Nguyen SA, Day TA (2014) Initial symptoms in patients with HPV-positive and HPV-negative oropharyngeal cancer. JAMA Otolaryngol Head Neck Surg 140(5):441–447. https://doi.org/10.1001/jamaoto.2014.141 CrossRefPubMed

38.

Lui VW, Hedberg ML, Li H, Vangara BS, Pendleton K, Zeng Y, Lu Y, Zhang Q, Du Y, Gilbert BR, Freilino M, Sauerwein S, Peyser ND, Xiao D, Diergaarde B, Wang L, Chiosea S, Seethala R, Johnson JT, Kim S, Duvvuri U, Ferris RL, Romkes M, Nukui T, Kwok-Shing Ng P, Garraway LA, Hammerman PS, Mills GB, Grandis JR (2013) Frequent mutation of the PI3K pathway in head and neck cancer defines predictive biomarkers. Cancer Discov 3(7):761–769. https://doi.org/10.1158/2159-8290.CD-13-0103 CrossRefPubMedPubMedCentral

39.

Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A, Shefler E, Ramos AH, Stojanov P, Carter SL, Voet D, Cortes ML, Auclair D, Berger MF, Saksena G, Guiducci C, Onofrio RC, Parkin M, Romkes M, Weissfeld JL, Seethala RR, Wang L, Rangel-Escareno C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Winckler W, Ardlie K, Gabriel SB, Meyerson M, Lander ES, Getz G, Golub TR, Garraway LA, Grandis JR (2011) The mutational landscape of head and neck squamous cell carcinoma. Science 333(6046):1157–1160. https://doi.org/10.1126/science.1208130 CrossRefPubMedPubMedCentral

40.

Pickering CR, Zhang J, Yoo SY, Bengtsson L, Moorthy S, Neskey DM, Zhao M, Ortega Alves MV, Chang K, Drummond J, Cortez E, Xie TX, Zhang D, Chung W, Issa JP, Zweidler-McKay PA, Wu X, El-Naggar AK, Weinstein JN, Wang J, Muzny DM, Gibbs RA, Wheeler DA, Myers JN, Frederick MJ (2013) Integrative genomic characterization of oral squamous cell carcinoma identifies frequent somatic drivers. Cancer Discov 3(7):770–781. https://doi.org/10.1158/2159-8290.CD-12-0537 CrossRefPubMed

41.

Agrawal N, Frederick MJ, Pickering CR, Bettegowda C, Chang K, Li RJ, Fakhry C, Xie TX, Zhang J, Wang J, Zhang N, El-Naggar AK, Jasser SA, Weinstein JN, Trevino L, Drummond JA, Muzny DM, Wu Y, Wood LD, Hruban RH, Westra WH, Koch WM, Califano JA, Gibbs RA, Sidransky D, Vogelstein B, Velculescu VE, Papadopoulos N, Wheeler DA, Kinzler KW, Myers JN (2011) Exome sequencing of head and neck squamous cell carcinoma reveals inactivating mutations in NOTCH1. Science 333(6046):1154–1157. https://doi.org/10.1126/science.1206923 CrossRefPubMedPubMedCentral

42.

Mountzios G, Rampias T, Psyrri A (2014) The mutational spectrum of squamous-cell carcinoma of the head and neck: targetable genetic events and clinical impact. Ann Oncol 25(10):1889–1900. https://doi.org/10.1093/annonc/mdu143 CrossRefPubMed

43.

Cancer Genome Atlas Network (2015) Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature 517 (7536):576–582. https://doi.org/10.1038/nature14129

44.

Dakubo GD, Jakupciak JP, Birch-Machin MA, Parr RL (2007) Clinical implications and utility of field cancerization. Cancer Cell Int 7:2. https://doi.org/10.1186/1475-2867-7-2 CrossRefPubMedPubMedCentral

45.

Leemans CR, Braakhuis BJ, Brakenhoff RH (2011) The molecular biology of head and neck cancer. Nat Rev Cancer 11(1):9–22. https://doi.org/10.1038/nrc2982 CrossRefPubMed

46.

Poeta ML, Manola J, Goldwasser MA, Forastiere A, Benoit N, Califano JA, Ridge JA, Goodwin J, Kenady D, Saunders J, Westra W, Sidransky D, Koch WM (2007) TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med 357(25):2552–2561. https://doi.org/10.1056/NEJMoa073770 CrossRefPubMedPubMedCentral

47.

van Houten VM, Tabor MP, van den Brekel MW, Kummer JA, Denkers F, Dijkstra J, Leemans R, van der Waal I, Snow GB, Brakenhoff RH (2002) Mutated p53 as a molecular marker for the diagnosis of head and neck cancer. J Pathol 198(4):476–486. https://doi.org/10.1002/path.1242 CrossRefPubMed

48.

Balz V, Scheckenbach K, Gotte K, Bockmuhl U, Petersen I, Bier H (2003) Is the p53 inactivation frequency in squamous cell carcinomas of the head and neck underestimated? Analysis of p53 exons 2-11 and human papillomavirus 16/18 E6 transcripts in 123 unselected tumor specimens. Cancer Res 63(6):1188–1191PubMed

49.

Kutler DI, Auerbach AD, Satagopan J, Giampietro PF, Batish SD, Huvos AG, Goberdhan A, Shah JP, Singh B (2003) High incidence of head and neck squamous cell carcinoma in patients with Fanconi anemia. Arch Otolaryngol Head Neck Surg 129(1):106–112CrossRefPubMed

50.

Hopkins J, Cescon DW, Tse D, Bradbury P, Xu W, Ma C, Wheatley-Price P, Waldron J, Goldstein D, Meyer F, Bairati I, Liu G (2008) Genetic polymorphisms and head and neck cancer outcomes: a review. Cancer Epidemiol Biomarkers Prev 17(3):490–499. https://doi.org/10.1158/1055-9965.EPI-07-2714 CrossRefPubMed

51.

Smith RB, Sniezek JC, Weed DT, Wax MK (2007) Utilization of free tissue transfer in head and neck surgery. Otolaryngol Head Neck Surg 137(2):182–191. https://doi.org/10.1016/j.otohns.2007.04.011 CrossRefPubMed

52.

Koch WM, Brennan JA, Zahurak M, Goodman SN, Westra WH, Schwab D, Yoo GH, Lee DJ, Forastiere AA, Sidransky D (1996) p53 mutation and locoregional treatment failure in head and neck squamous cell carcinoma. J Natl Cancer Inst 88(21):1580–1586CrossRefPubMed

53.

Graveland AP, Golusinski PJ, Buijze M, Douma R, Sons N, Kuik DJ, Bloemena E, Leemans CR, Brakenhoff RH, Braakhuis BJ (2011) Loss of heterozygosity at 9p and p53 immunopositivity in surgical margins predict local relapse in head and neck squamous cell carcinoma. Int J Cancer 128(8):1852–1859. https://doi.org/10.1002/ijc.25523 CrossRefPubMed

54.

Ying J, Li H, Seng TJ, Langford C, Srivastava G, Tsao SW, Putti T, Murray P, Chan AT, Tao Q (2006) Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation. Oncogene 25(7):1070–1080. https://doi.org/10.1038/sj.onc.1209154 CrossRefPubMed

55.

Don KR, Ramani P, Ramshankar V, Sherlin HJ, Premkumar P, Natesan A (2014) Promoter hypermethylation patterns of P16, DAPK and MGMT in oral squamous cell carcinoma: a systematic review and meta-analysis. Indian J Dent Res 25(6):797–805. https://doi.org/10.4103/0970-9290.152208 CrossRefPubMed

56.

Sanchez-Cespedes M, Esteller M, Wu L, Nawroz-Danish H, Yoo GH, Koch WM, Jen J, Herman JG, Sidransky D (2000) Gene promoter hypermethylation in tumors and serum of head and neck cancer patients. Cancer Res 60(4):892–895PubMed

57.

Noorlag R, van Kempen PM, Moelans CB, de Jong R, Blok LE, Koole R, Grolman W, van Diest PJ, van Es RJ, Willems SM (2014) Promoter hypermethylation using 24-gene array in early head and neck cancer: better outcome in oral than in oropharyngeal cancer. Epigenetics 9(9):1220–1227. https://doi.org/10.4161/epi.29785 CrossRefPubMedPubMedCentral

58.

van Kempen PM, Noorlag R, Braunius WW, Stegeman I, Willems SM, Grolman W (2014) Differences in methylation profiles between HPV-positive and HPV-negative oropharynx squamous cell carcinoma: a systematic review. Epigenetics 9(2):194–203. https://doi.org/10.4161/epi.26881 CrossRefPubMed

59.

Sartor MA, Dolinoy DC, Jones TR, Colacino JA, Prince ME, Carey TE, Rozek LS (2011) Genome-wide methylation and expression differences in HPV(+) and HPV(−) squamous cell carcinoma cell lines are consistent with divergent mechanisms of carcinogenesis. Epigenetics 6(6):777–787CrossRefPubMedPubMedCentral

60.

Choudhury JH, Ghosh SK (2015) Promoter hypermethylation profiling identifies subtypes of head and neck cancer with distinct viral, environmental, genetic and survival characteristics. PLoS One 10(6):e0129808. https://doi.org/10.1371/journal.pone.0129808 CrossRefPubMedPubMedCentral

61.

Kostareli E, Holzinger D, Bogatyrova O, Hielscher T, Wichmann G, Keck M, Lahrmann B, Grabe N, Flechtenmacher C, Schmidt CR, Seiwert T, Dyckhoff G, Dietz A, Hofler D, Pawlita M, Benner A, Bosch FX, Plinkert P, Plass C, Weichenhan D, Hess J (2013) HPV-related methylation signature predicts survival in oropharyngeal squamous cell carcinomas. J Clin Invest 123(6):2488–2501. https://doi.org/10.1172/JCI67010 CrossRefPubMedPubMedCentral

62.

Tokumaru Y, Yamashita K, Osada M, Nomoto S, Sun DI, Xiao Y, Hoque MO, Westra WH, Califano JA, Sidransky D (2004) Inverse correlation between cyclin A1 hypermethylation and p53 mutation in head and neck cancer identified by reversal of epigenetic silencing. Cancer Res 64(17):5982–5987. https://doi.org/10.1158/0008-5472.CAN-04-0993 CrossRefPubMed

63.

Perdomo S, Martin Roa G, Brennan P, Forman D, Sierra MS (2016) Head and neck cancer burden and preventive measures in Central and South America. Cancer Epidemiol 44(Suppl 1):S43–S52. https://doi.org/10.1016/j.canep.2016.03.012 CrossRefPubMed

64.

Lopez CR, Antoni MH, Pereira D, Seay J, Whitehead N, Potter J, O'Sullivan M, Fletcher MA (2013) Stress management, depression and immune status in lower income racial/ethnic minority women co-infected with HIV and HPV. J Appl Biobehav Res 18(1):37–57. https://doi.org/10.1111/jabr.12003 CrossRefPubMedPubMedCentral

Title: Clinical and Molecular Characterization of Surgically Treated Oropharynx Squamous Cell Carcinoma Samples
Authors: Ana Carolina de Carvalho
Matias Eliseo Melendez
Cristina da Silva Sabato
Edenir Inez Palmero
Lidia Maria Rebolho Batista Arantes
Cristovam Scapulatempo Neto
André Lopes Carvalho
Publication date: 01-07-2019
Publisher: Springer Netherlands
Published in: Pathology & Oncology Research / Issue 3/2019
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-018-0462-0

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2019

Thyroid Carcinoma Coexisting with Hashimoto’s Thyreoiditis: Clinicopathological and Molecular Characteristics Clue up Pathogenesis

Research Progresses in Cancer Stem Cells of Three Common Fertility-Related Female Malignancies

Diagnostic Value of Circulating Free DNA Integrity and Global Methylation Status in Gall Bladder Carcinoma

IDH Mutation Analysis in Glioma Patients by CADMA Compared with SNaPshot Assay and two Immunohistochemical Methods

Real Life Data on Efficacy and Safety of Azacitidine Therapy for Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia

MEG3: an Oncogenic Long Non-coding RNA in Different Cancers

Keynote webinar | Spotlight on antibody–drug conjugates in cancer