Abstract
Saliva is one of the most valuable body fluids after blood. Although its function may seem to originally be confined to the local environment, the alterations in the salivary composition, quality and quantity, may reflect numerous pathologies and systemic diseases including cancer.
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References
Abdolsamadi H, Rafieian N, Goodarzi MT, Feradmal J, Davoodi P, Jazayeri M, Taghavi Z, Hoseyni SM, Ahmadi-Motamayel F (2014) Levels of salivary antioxidant vitamins and lipid peroxidation in patients with oral lichen planus and healthy individuals. Chonnam Med J 50(2):58–62
Adams L, Roth MJ, Abnet CC, Dawsey SP, Qiao YL, Wang GQ, Wei WQ, Lu N, Dawsey SM, Woodson K (2008) Promoter methylation in cytology specimens as an early detection marker for esophageal squamous dysplasia and early esophageal squamous cell carcinoma. Cancer Prev Res (Phila) 1(5):357–361
Ahn SM, Chan JY, Zhang Z, Wang H, Khan Z, Bishop JA, Westra W, Koch WM, Califano JA (2014) Saliva and plasma quantitative polymerase chain reaction-based detection and surveillance of human papillomavirus-related head and neck cancer. JAMA Otolaryngol Head Neck Surg 140(9):846–854
Ajona D, Pajares MJ, Chiara MD, Rodrigo JP, Jantus-Lewintre E, Camps C, Suarez C, Bagan JV, Montuenga LM, Pio R (2015) Complement activation product C4d in oral and oropharyngeal squamous cell carcinoma. Oral Dis 21(7):899–904
Alvarez PB, Sayans MP, Iruegas EP, Penaranda JMS, Alves MO, Carrion AB, Garcia AG (2018) State of methylation and epigenome studies in some types of head and neck cancer. Biomed Res 29(14). https://doi.org/10.4066/biomedicalresearch.29-18-104
Andreu Z, Yáñez-Mó M (2014) Tetraspanins in extracellular vesicle formation and function. Front Immunol 5:442
Arantes LM, de Carvalho AC, Melendez ME, Carvalho AL, Goloni-Bertollo EM (2014) Methylation as a biomarker for head and neck cancer. Oral Oncol 50(6):587–592
Arantes LM, de Carvalho AC, Melendez ME, Centrone CC, Góis-Filho JF, Toporcov TN, Caly DN, Tajara EH, Goloni-Bertollo EM, Carvalho AL, GENCAPO (2015) Validation of methylation markers for diagnosis of oral cavity cancer. Eur J Cancer 51(5):632–641
Ayinampudi BK, Narsimhan M (2012) Salivary copper and zinc levels in oral pre-malignant and malignant lesions. Journal of oral and maxillofacial pathology: JOMFP 16(2):178
Bagan JV, Scully C (2008) Recent advances in oral oncology 2007: epidemiology, aetiopathogenesis, diagnosis and prognostication. Oral Oncol 44(2):103–108
Battino M, Greabu M, Totan A, Bullon P, Bucur A, Tovaru S, Mohora M, Didilescu A, Parlatescu I, Spinu T, Totan C (2008) Oxidative stress markers in oral lichen planus. Biofactors (Oxford, England) 33(4):301–310
Baum BJ (1993) Principles of saliva secretion. Ann N Y Acad Sci 694(1):17–23
Bhatia V, Goel MM, Makker A, Tewari S, Yadu A, Shilpi P, Kumar S, Agarwal SP, Goel SK (2014) Promoter region hypermethylation and mRNA expression of MGMT and p16 genes in tissue and blood samples of human premalignant oral lesions and oral squamous cell carcinoma. Biomed Res Int 2014:248419
Brailo V, Vucicevic-Boras V, Cekic-Arambasin A, Alajbeg IZ, Milenovic A, Lukac J (2006) The significance of salivary interleukin 6 and tumor necrosis factor alpha in patients with oral leucoplakia. Oral Oncol 42(4):370–373
Brailo V, Vucicevic-boras V, Lukac J, Biocina-lukenda D, Zilic-alajbeg I, Milenovic A, Balija M (2012) Salivary and serum interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha in patients with leukoplakia and oral cancer. Medicina oral, patologia oral y cirugia bucal 17(1):10
Brinkman BM, Wong DT (2006) Disease mechanism and biomarkers of oral squamous cell carcinoma. Curr Opin Oncol 18(3):228–233
Bryan AD, Magnan RE, Hooper AE, Harlaar N, Hutchison KE (2013) Physical activity and differential methylation of breast cancer genes assayed from saliva: a preliminary investigation. Ann Behav Med 45(1):89–98
Byun JS, Hong SH, Choi JK, Jung JK, Lee HJ (2015) Diagnostic profiling of salivary exosomal microRNAs in oral lichen planus patients. Oral Dis 21(8):987–993
Camisasca DR, da Rosgoncalves L, Soares MR, Sandim V, Nogueira FC, Garcia CH, Santana R, de Oliveira SP, Buexm LA, de Faria PA, Dias FL, Pereira DA, Zingali RB, Alves G, Lourenco SQ (2017) A proteomic approach to compare saliva from individuals with and without oral leucoplakia. J Proteome 151:43–52
Cao J, Zhou J, Gao Y, Gu L, Meng H, Liu H, Deng D (2009) Methylation of p16 CpG island associated with malignant progression of oral epithelial dysplasia: a prospective cohort study. Clin Cancer Res 15(16):5178–5183
Cao Y, Green K, Quattlebaum S, Milam B, Lu L, Gao D, He H, Li N, Gao L, Hall F, Whinery M, Handley E, Ma Y, Xu T, Jin F, Xiao J, Wei M, Smith D, Bornstein S, Gross N, Pyeon D, Song J, Lu SL (2018) Methylated genomic loci encoding microRNA as a biomarker panel in tissue and saliva for head and neck squamous cell carcinoma. Clin Epigenetics 10:43
Carvalho AL, Jeronimo C, Kim MM, Henrique R, Zhang Z, Hoque MO, Chang S, Brait M, Nayak CS, Jiang WW, Claybourne Q, Tokumaru Y, Lee J, Goldenberg D, Garrett-Mayer E, Goodman S, Moon CS, Koch W, Westra WH, Sidransky D, Califano JA (2008) Evaluation of promoter hypermethylation detection in body fluids as a screening/diagnosis tool for head and neck squamous cell carcinoma. Clin Cancer Res 14(1):97–107
Carvalho AL, Henrique R, Jeronimo C, Nayak CS, Reddy AN, Hoque MO, Califano JA (2011) Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance. Clin Cancer Res 17(14):4782–4789
Chang HW, Chow V, Lam KY, Wei WI, Yuen A (2002) Loss of E-cadherin expression resulting from promoter hypermethylation in oral tongue carcinoma and its prognostic significance. Cancer 94(2):386–392. https://doi.org/10.1002/cncr.10211
Chuang AY, Chuang TC, Chang S, Zhou S, Begum S, Westra WH, Ha PK, Koch WM, Califano JA (2008) Presence of HPV DNA in convalescent salivary rinses is an adverse prognostic marker in head and neck squamous cell carcinoma. Oral Oncol 44(10):915–919
Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A (2013) Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol 10(8):472
Cuevas-Cordoba B, Santiago-Garcia J (2014) Saliva: a fluid of study for OMICS. Omics: J Integr Biol 18(2):87–97
Dang J, Bian YQ, Sun JY, Chen F, Dong GY, Liu Q, Wang XW, Kjems J, Gao S, Wang QT (2013) MicroRNA-137 promoter methylation in oral lichen planus and oral squamous cell carcinoma. J Oral Pathol Med 42(4):315–321
De Jong EP, Xie H, Onsongo G, Stone MD, Chen XB, Kooren JA, Refsland EW, Griffin RJ, Ondrey FG, Wu B, Le CT, Rhodus NL, Carlis JV, Griffin TJ (2010) Quantitative proteomics reveals myosin and actin as promising saliva biomarkers for distinguishing pre-malignant and malignant oral lesions. PLoS One 5(6):E11148
De A, Sparreboom W, van den Berg A, Carlen ET (2014) Rapid microfluidic solid-phase extraction system for hyper-methylated DNA enrichment and epigenetic analysis. Biomicrofluidics 8(5):054119
Demokan S, Dalay N (2011) Role of DNA methylation in head and neck cancer. Clin Epigenetics 2(2):123–150. https://doi.org/10.1007/s13148-011-0045-3. Epub 2011 Jul 9
Ding F, Sun K, Sun N, Jiang Q, Cao M, Wu Z (2019) iTRAQ-based proteomics reveals SOD2 as a potential salivary biomarker in liver cancer. Int J Biol Markers 34(3):221–231
Dowling P, Wormald R, Meleady P, Henry M, Curran A, Clynes M (2008) Analysis of the saliva proteome from patients with head and neck squamous cell carcinoma reveals differences in abundance levels of proteins associated with tumour progression and metastasis. J Proteome 71(2):168–175
Epstein JB, Zhang L, Rosin M (2002) Advances in the diagnosis of oral premalignant and malignant lesions. J Can Dent Assoc 68(10):617–621
Fais S, Logozzi M, Lugini L, Federici C, Azzarito T, Zarovni N, Chiesi A (2013) Exosomes: the ideal nanovectors for biodelivery. Biol Chem 394(1):1–15
Fang L, Liu Q, He P, Wang X, Wang Y, Wei M, Chen L (2018) Alteration of salivary glycopatterns in oral lichen planus. Biomarkers 23(2):188–195
Ferlazzo N, Currò M, Zinellu A, Caccamo D, Isola G, Ventura V, Carru C, Matarese G, Ientile R (2017) Influence of MTHFR genetic background on p16 and MGMT methylation in oral squamous cell cancer. Int J Mol Sci 18(4)
Flores IL, Santos-Silva AR, Coletta RD, Leme AF, Lopes MA (2016) Low expression of angiotensinogen and dipeptidyl peptidase 1 in saliva of patients with proliferative verrucous leucoplakia. World J Clin Cases 4(11):356–363
Franzmann EJ, Reategui EP, Pedroso F, Pernas FG, Karakullukcu BM, Carraway KL, Hamilton K, Singal R, Goodwin WJ (2007) Soluble CD44 is a potential marker for the early detection of head and neck cancer. Cancer Epidemiol Biomark Prev 16:1348–1355
Galetzka D, Hansmann T, El Hajj N, Weis E, Irmscher B, Ludwig M et al (2012) Monozygotic twins discordant for constitutive BRCA1 promoter methylation, childhood cancer and secondary cancer. Epigenetics 7(1):47–54. https://doi.org/10.4161/epi.7.1.18814
Gallo C, Ciavarella D, Santarelli A, Ranieri E, Colella G, Lo Muzio L, Lo Russo L (2016) Potential salivary proteomic markers of oral squamous cell carcinoma. Cancer Genomics Proteomics 13(1):55–61
Gandara-Vila P, Pérez-Sayans M, Suárez-Peñaranda JM, Gallas-Torreira M, Somoza-Martín J, Reboiras-López M, Blanco-Carrión A, García-García A (2018) Survival study of leucoplakia malignant transformation in a region of northern Spain. Med Oral Patol Oral y Cir Bucal 23(4):E413
Garcia-Pola MJ, Gonzalez-Alvarez L, Garcia-Martin JM (2017) Treatment of oral lichen planus. Systematic review and therapeutic guide. Med Clin 149(8):351–362
Gardner KR, Sapienza C, Fisher JO (2015) Genetic and epigenetic associations to obesity-related appetite phenotypes among African-American children. Pediatr Obes 10(6):476–482
Germi R, Guigue N, Lupo J, Semenova T, Grossi L, Vermeulen O, Epaulard O, de Fraipont F, Morand P (2016) Methylation of Epstein-Barr virus Rta promoter in EBV primary infection, reactivation and lymphoproliferation. J Med Virol 88(10):1814–1820
Ghallab, N.A., El-Wakeel, N. And Shaker, O.G., 2010. Levels of salivary IFN-gamma, TNF-alfa, and TNF receptor-2 as prognostic markers in (erosive) oral lichen planus. Mediat Inflamm, 2010, pp. 847632
Ghosh A, Ghosh S, Maiti GP, Sabbir MG, Alam N, Sikdar N, Roy B, Roychoudhury S, Panda CK (2009) SH3GL2 and CDKN2A/2B loci are independently altered in early dysplastic lesions of head and neck: correlation with HPV infection and tobacco habit. J Pathol 217(3):408–419
Godderis L, Schouteden C, Tabish A, Poels K, Hoet P, Baccarelli AA, Van Landuyt K (2015) Global methylation and hydroxymethylation in DNA from blood and saliva in healthy volunteers. Biomed Res Int 2015:845041
Guerrero-Preston R, Soudry E, Acero J, Orera M, Moreno-López L, Macía-Colón G, Jaffe A, Berdasco M, Ili-Gangas C, Brebi-Mieville P, Fu Y, Engstrom C, Irizarry RA, Esteller M, Westra W, Koch W, Califano J, Sidransky D (2011) NID2 and HOXA9 promoter hypermethylation as biomarkers for prevention and early detection in oral cavity squamous cell carcinoma tissues and saliva. Cancer Prev Res (Phila) 4(7):1061–1072
Guerra ENS, Rêgo DF, Elias ST, Coletta RD, Mezzomo LAM, Gozal D, Canto GDL (2016) Diagnostic accuracy of serum biomarkers for head and neck cancer: a systematic review and meta-analysis. Crit Rev Oncol Hematol 101:93–118
Guo W, Gao Y, Li N, Shao F, Wang C, Wang P, Yang Z, Li R, He J (2017) Exosomes: new players in cancer (review). Oncol Rep 38(2):665–675
Gyobu K, Yamashita S, Matsuda Y, Igaki H, Niwa T, Oka D, Kushima R, Osugi H, Lee S, Suehiro S, Ushijima T (2011) Identification and validation of DNA methylation markers to predict lymph node metastasis of esophageal squamous cell carcinomas. Ann Surg Oncol 18(4):1185–1194
Hayes DF, Bast RC, Desch CE, Fritsche H Jr, Kemeny NE, Jessup JM et al (1996) Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers. JNCI: J Natl Cancer Inst 88(20):1456–1466
Hema KN, Smitha T, Sheethal HS, Mirnalini SA (2017) Epigenetics in oral squamous cell carcinoma. J Oral Maxillofac Pathol 21(2):252–259
Hoffmann RR, Yurgel LS, Campos MM (2011) Evaluation of salivary endothelin-1 levels in oral squamous cell carcinoma and oral leucoplakia. Regul Pept 166(1–3):55–58
Hood JL, San RS, Wickline SA (2011) Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res 71(11):3792–3801
Hooper SJ, Wilson MJ, Crean SJ (2009) Exploring the link between microorganisms and oral cancer: a systematic review of the literature. Head Neck 31(9):1228–1239
Hu S, Arellano M, Boontheung P, Wang J, Zhou H, Jiang J, Elashoff D, Wei R, Loo JA, Wong DT (2008) Salivary proteomics for oral cancer biomarker discovery. Clin Cancer Res 14(19):6246–6252
Hu X, Zhang Q, Hua H, Chen F (2016) Changes in the salivary microbiota of oral leucoplakia and oral cancer. Oral Oncol 56:E6–E8
Huang XF, Li W, Yang XD, Jiang WH, Chen XH, Hu QG (2012) Keratocystoma of the parotid gland: a clinicopathological study and literature review. Int J Oral Maxillofac Surg 41(2):256–260
Humeau M, Vignolle-Vidoni A, Sicard F, Martins F, Bournet B, Buscail L, Torrisani J, Cordelier P (2015) Salivary microRNA in pancreatic cancer patients. PLoS One 10(6):e0130996
Hung KF, Liu CJ, Chiu PC, Lin JS, Chang KW, Shih WY, Kao SY, Tu HF (2016) Microrna-31 upregulation predicts increased risk of progression of oral potentially malignant disorder. Oral Oncol 53:42–47
Ishikawa S, Sugimoto M, Kitabatake K, Tu M, Sugano A, Yamamori I, Iba A, Yusa K, Kaneko M, Ota S, Hiwatari K, Enomoto A, Masaru T, Iino M (2017) Effect of timing of collection of salivary metabolomic biomarkers on oral cancer detection. Amino Acids 49(4):761–770
Jaeger F, Assuncao AC, Caldeira PC, Queiroz-Junior CM, Bernardes VF, De Aguiar MC (2015) Is salivary epidermal growth factor a biomarker for oral leucoplakia? A preliminary study. Oral Surg Oral Med Oral Pathol Oral Radiol 119(4):451–458
Jessie K, Jayapalan JJ, Ong KC, Abdul Rahim ZH, Zain RM, Wong KT, Hashim OH (2013) Aberrant proteins in the saliva of patients with oral squamous cell carcinoma. Electrophoresis 34(17):2495–2502
Ji ZW, Oku N, Umeda M, Komori T (2001) Establishment of an oral squamous cell carcinoma cell line (NOS-1) exhibiting amplification of the erbb-1 oncogene and point mutation of p53 tumor suppressor gene: its biological characteristics and animal model of local invasion by orthotopic transplantation of the cell line. Oral Oncol 37(4):386–392
Ji X, Guan C, Jiang X, Li H (2016) Diagnostic accuracy of DNA methylation for head and neck cancer varies by sample type and number of markers tested. Oncotarget 7(48):80019–80032
Jiang WW, Masayesva B, Zahurak M, Carvalho AL, Rosenbaum E, Mambo E, Zhou S, Minhas K, Benoit N, Westra WH, Alberg A, Sidransky D, Koch W, Califano J (2005) Increased mitochondrial DNA content in saliva associated with head and neck cancer. Clin Cancer Res 11(7):2486–2491
Joseph BK (2002) Oral cancer: prevention and detection. Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre 11(Suppl 1):32–35
Jou YJ, Lin CD, Lai CH, Chen CH, Kao JY, Chen SY, Tsai MH, Huang SH, Lin CW (2010) Proteomic identification of salivary transferrin as a biomarker for early detection of oral cancer. Anal Chim Acta 681(1–2):41–48
Kang JH, Kho HS (2018) Blood contamination in salivary diagnostics: current methods and their limitations. Clin Chem Lab Med 57(8):1115–1124
Kaur J, Demokan S, Tripathi SC, Macha MA, Begum S, Califano JA, Ralhan R (2010) Promoter hypermethylation in Indian primary oral squamous cell carcinoma. Int J Cancer 127(10):2367–2373
Kaur J, Politis C, Jacobs R (2016) Salivary 8-hydroxy-2-deoxyguanosine, malondialdehyde, vitamin C, and vitamin E in oral pre-cancer and cancer: diagnostic value and free radical mechanism of action. Clin Oral Investig 20(2):315–319
Kaur J, Jacobs R, Huang Y, Salvo N, Politis C (2018) Salivary biomarkers for oral cancer and pre-cancer screening: a review. Clin Oral Investig 22(2):633–640
Khurshid Z, Zafar MS, Khan RS, Najeeb S, Slowey PD, Rehman IU (2018) Role of salivary biomarkers in oral cancer detection. Adv Clin Chem 86:23–70
Killian JK, Miettinen M, Walker RL, Wang Y, Zhu YJ, Waterfall JJ et al (2014) Recurrent epimutation of SDHC in gastrointestinal stromal tumors. Sci Transl Med 6(268):268ra177. https://doi.org/10.1126/scitranslmed.3009961
Kim BW, Esworthy RS, Hahn MA, Pfeifer GP, Chu FF (2012) Expression of lactoperoxidase in differentiated mouse colon epithelial cells. Free Radic Biol Med 52(9):1569–1576
Kim J, Shin H, Park J (2017) RNA in salivary extracellular vesicles as a possible tool for systemic disease diagnosis. J Dent Res 96(8):938–944
King HW, Michael MZ, Gleadle JM (2012) Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer 12(1):421
Kis A, Tatár TZ, Gáll T, Boda R, Tar I, Major T, Redl P, Gergely L, Pathol SK (2014) Frequency of genetic and epigenetic alterations of p14ARF and p16INK4A in head and neck cancer in a Hungarian population. Oncol Res 20(4):923–929
Kobayashi T, Maruyama S, Abe T, Cheng J, Takagi R, Saito C, Saku T (2012) Keratin 10-positive orthokeratotic dysplasia: a new leucoplakia-type precancerous entity of the oral mucosa. Histopathology 61(5):910–920
Krapfenbauer K, Drucker E, Thurnher D (2014) Identification of tumour-related proteins as potential screening markers by proteome analysis-protein profiles of human saliva as a predictive and prognostic tool. EPMA J 5(1), pp 20-5085-5-20. Ecollection 2014
Kulkarni V, Saranath D (2004) Concurrent hypermethylation of multiple regulatory genes in chewing tobacco associated oral squamous cell carcinomas and adjacent normal tissues. Oral Oncol 40:145–153
Kumeda N, Ogawa Y, Akimoto Y, Kawakami H, Tsujimoto M, Yanoshita R (2017) Characterization of membrane integrity and morphological stability of human salivary exosomes. Biol Pharm Bull 40(8):1183–1191
Langie SAS, Moisse M, Declerck K, Koppen G, Godderis L, Vanden Berghe W et al (2017a) Salivary DNA methylation profiling: aspects to consider for biomarker identification. Basic Clin Pharmacol Toxicol 121(Suppl 3):93–101
Langie SAS, SzarcVelSzic K, Declerck K, Traen S, Koppen G, Van Camp G et al (2017b) Correction: whole-genome saliva and blood DNA methylation profiling in individuals with a respiratory allergy. Plos One 12(8):e0183088
Larsen KR, Johansen JD, Reibel J, Zachariae C, Rosing K, Pedersen AML (2017) Oral symptoms and salivary findings in oral lichen planus, oral lichenoid lesions and stomatitis. BMC Oral Health 17(1):2
Laytragoon-Lewin N, Chen F, Castro J, Elmberger G, Rutqvist LE, Lewin F, Turesson I, Lundgren J (2010) DNA content and methylation of p16, DAPK and RASSF1A gene in tumour and distant, normal mucosal tissue of head and neck squamous cell carcinoma patients. Anticancer Res 30(11):4643–4648
Lee Y, El Andaloussi S, Wood MJA (2012a) Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet 21(R1):125
Lee YH, Kim JH, Zhou H, Kim BW, Wong DT (2012b) Salivary transcriptomic biomarkers for detection of ovarian cancer: for serous papillary adenocarcinoma. J Mol Med (Berl) 90(4):427–434
Lee WH, Chen HM, Yang SF, Liang C, Peng CY, Lin FM, Tsai LL, Wu BC, Hsin CH, Chuang CY, Yang T, Yang TL, Ho SY, Chen WL, Ueng KC, Huang HD, Huang CN, Jong YJ (2017) Bacterial alterations in salivary microbiota and their association in oral cancer. Sci Rep 7(1):16540-017-16418-x
Lengacher CA, Reich RR, Paterson CL, Shelton M, Shivers S, Ramesar S et al (2018) A large randomized trial: effects of mindfulness-based stress reduction (MBSR) for breast cancer (BC) survivors on salivary cortisol and IL-6. Biol Res Nurs 21(1):39–49
Leon SA, Ehrlich GE, Shapiro B, Labbate VA (1977) Free DNA in the serum of rheumatoid arthritis patients. J Rheumatol 4(2):139–143
Li B, Wang B, Niu LJ, Jiang L, Qiu CC (2011) Hypermethylation of multiple tumor-related genes associated with DNMT3b up-regulation served as a biomarker for early diagnosis of esophageal squamous cell carcinoma. Epigenetics 6:307–316
Li L, Li C, Wang S, Wang Z, Jiang J, Wang W, Li X, Chen J, Liu K, Li C, Zhu G (2016) Exosomes derived from hypoxic oral squamous cell carcinoma cells deliver miR-21 to normoxic cells to elicit a prometastatic phenotype. Cancer Res 76(7):1770–1780
Liberti MV, Locasale JW (2016) The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci 41(3):211–218
Lim Y, Sun CX, Tran P, Punyadeera C (2016a) Salivary epigenetic biomarkers in head and neck squamous cell carcinomas. Biomark Med 10(3):301–313. https://doi.org/10.2217/bmm.16.2
Lim Y, Wan Y, Vagenas D, Ovchinnikov D, Perry C, Davis M, Punyadeera C (2016b) Salivary DNA methylation panel to diagnose HPV-positive and HPV-negative head and neck cancers. BMC Cancer 16:749
Liu C, Yu S, Zinn K, Wang J, Zhang L, Jia Y, Kappes JC, Barnes S, Kimberly RP, Grizzle WE, Zhang HG (2006) Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. J Immunol (Baltimore, Md: 1950) 176(3):1375–1385
Liu CJ, Lin SC, Yang CC, CHENG HW, Chang KW (2012a) Exploiting salivary miR-31 as a clinical biomarker of oral squamous cell carcinoma. Head Neck 34(2):219–224
Liu Y, Zhou ZT, He QB, Jiang WW (2012b) DAPK promoter hypermethylation in tissues and body fluids of oral precancer patients. Medical Oncology (Northwood, London, England) 29(2):729–733
Liu K, Zhang Y, Zhang C, Zhang Q, Li J, Xiao F, Li Y, Zhang R, Dou D, Liang J, Qin J, Lin Z, Zhao D, Jiang M, Liang Z, Su J, Gupta VP, He M, Yang X (2016) Methylation of S100A8 is a promising diagnosis and prognostic marker in hepatocellular carcinoma. Oncotarget 7(35):56798–56810
Lodi G, Scully C, Carrozzo M, Griffiths M, Sugerman PB, Thongprasom K (2005) Current controversies in oral lichen planus: report of an international consensus meeting. Part 2. Clinical management and malignant transformation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 100(2):164–178
Logozzi M, De Milito A, Lugini L, Borghi M, Calabrò L, Spada M, Perdicchio M, Marino ML, Federici C, Iessi E, Brambilla D, Venturi G, Lozupone F, Santinami M, Huber V, Maio M, Rivoltini L, Fais S (2009) High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients. PLoS One 4(4):E5219
Lopez M, Aguirre JM, Cuevas N, Anzola M, Videgain J, Aguirregaviria J, Martinez de Pancorbo M (2003) Gene promoter hypermethylation in oral rinses of leucoplakia patients–A diagnostic and/or prognostic tool? Eur J Cancer (Oxford, England: 1990) 39(16):2306–2309
Loyo M, Brait M, Kim MS, Ostrow KL, Jie CC, Chuang AY, Califano JA, Liégeois NJ, Begum S, Westra WH, Hoque MO, Tao Q, Sidransky D (2011) A survey of methylated candidate tumor suppressor genes in nasopharyngeal carcinoma. Int J Cancer 128(6):1393–1403
Ludwig JA, Weinstein JN (2005) Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer 5(11):845
Ma H, Wu Y, Yang H, Liu J, Dan H, Zeng X, Zhou Y, Jiang L, Chen Q (2016) MicroRNAs in oral lichen planus and potential miRNA-mRNA pathogenesis with essential cytokines: a review. Oral Surg Oral Med Oral Pathol Oral Radiol 122(2):164–173
Maeda G, Chiba T, Aoba T, Imai K (2007) Epigenetic inactivation of E-cadherin by promoter hypermethylation in oral carcinoma cells. Odontology/the Society of the Nippon Dental University 95(1):24–29
Mager DL, Haffajee AD, Devlin PM, Norris CM, Posner MR, Goodson JM (2005) The salivary microbiota as a diagnostic indicator of oral cancer: a descriptive, non-randomized study of cancer-free and oral squamous cell carcinoma subjects. J Transl Med 3:27-5876-3-27
Malathi N, Mythili S, Vasanthi HR (2014) Salivary diagnostics: a brief review. ISRN Dent 2014
Markopoulou S, Nikolaidis G, Liloglou T (2012) DNA methylation biomarkers in biological fluids for early detection of respiratory tract cancer. Clin Chem Lab Med 50(10):1723–1731. https://doi.org/10.1515/cclm-2012-0124
Martone T, Gillio-Tos A, De Marco L, Fiano V, Maule M, Cavalot A, Garzaro M, Merletti F, Cortesina G (2007) Association between hypermethylated tumor and paired surgical margins in head and neck squamous cell carcinomas. Clin Cancer Res 13:5089–5094
Maruya S, Issa JP, Weber RS, Rosenthal DI, Haviland JC, Lotan R, El-Naggar AK (2004) Differential methylation status of tumor-associated genes in head and neck squamous carcinoma: incidence and potential implications. Clin Cancer Res 10:3825–3830
Matse JH, Yoshizawa J, Wang X, Elashoff D, Bolscher JG, Veerman EC, Leemans CR, Pegtel DM, Wong DT, Bloemena E (2015) Human salivary micro-RNA in patients with parotid salivary gland neoplasms. PLoS One 10(11):e0142264
Matse JH, Yoshizawa J, Wang X, Elashoff D, Bolscher JGM, Veerman ECI et al (2016) Correction: human salivary micro-RNA in patients with parotid salivary gland neoplasms. PLoS One 11(1):e0146701
Matthews AM, Kaur H, Dodd M, D’Souza J, Liloglou T, Shaw RJ, Risk JM (2013) Saliva collection methods for DNA biomarker analysis in oral cancer patients. Br J Oral Maxillofac Surg 51(5):394–398
Mcpherson RA, Pincus MR (2017) Henry’s clinical diagnosis and management by laboratory methods E-book Elsevier Health Sciences
Mehdipour M, Shahidi M, Manifar S, Jafari S, Mashhadi Abbas F, Barati M, Mortazavi H, Shirkhoda M, Farzanegan A, ElmiRankohi Z (2018) Diagnostic and prognostic relevance of salivary microrna-21, −125a, −31 and -200a levels in patients with oral lichen planus – a short report. Cell Oncol (Dordr) 41(3):329–334
Michailidou E, Tzimagiorgis G, Chatzopoulou F, Vahtsevanos K, Antoniadis K, Kouidou S, Markopoulos A, Antoniades D (2016) Salivary mRNA markers having the potential to detect oral squamous cell carcinoma segregated from oral leucoplakia with dysplasia. Cancer Epidemiol 43:112–118
Minor J, Wang X, Zhang F, Song J, Jimeno A, Wang XJ, Lu X, Gross N, Kulesz-Martin M, Wang D, Lu SL (2012) Methylation of microRNA-9 is a specific and sensitive biomarker for oral and oropharyngeal squamous cell carcinomas. Oral Oncol 48(1):73–78
Momen-Heravi F, Trachtenberg AJ, Kuo WP, Cheng YS (2014) Genomewide study of salivary microRNAs for detection of oral cancer. J Dent Res 93(7 suppl):93S
Nagler RM (2009) Saliva as a tool for oral cancer diagnosis and prognosis. Oral Oncol 45(12):1006–1010
Nagata S, Hamada T, Yamada N, Yokoyama S, Kitamoto S, Kanmura Y, Nomura M, Kamikawa Y, Yonezawa S, Sugihara K (2012) Aberrant DNA methylation of tumor-related genes in oral rinse: a noninvasive method for detection of oral squamous cell carcinoma. Cancer 118(17):4298–4308
Nair S, Tang KD, Kenny L, Punyadeera C (2018) Salivary exosomes as potential biomarkers in cancer. Oral Oncol 84:31–40
Nakahara Y, Shintani S, Mihara M, Ueyama Y, Matsumura T (2001) High frequency of homozygous deletion and methylation of p16(INK4A) gene in oral squamous cell carcinomas. Cancer Lett 163:221–228
Nakayama S, Sasaki A, Mese H, Alcalde RE, Tsuji T, Matsumura T (2001) The E-cadherin gene is silenced by CpG methylation in human oral squamous cell carcinomas. Int J Cancer 93(5):667–673
Nawaz I, Moumad K, Martorelli D, Ennaji MM, Zhou X, Zhang Z, Dolcetti R, Khyatti M, Ernberg I, Hu LF (2015) Detection of nasopharyngeal carcinoma in Morocco (North Africa) using a multiplex methylation-specific PCR biomarker assay. Clin Epigenetics 7:89
Nosratzehi T, Alijani E, Moodi M (2017) Salivary MMP-1, MMP-2, MMP-3 and MMP-13 levels in patients with Oral lichen planus and squamous cell carcinoma. Asian Pac J Cancer Prev 18(7):1947–1951
Nylander E, Ebrahimi M, Wahlin YB, Boldrup L, Nylander K (2012) Changes in miRNA expression in sera and correlation to duration of disease in patients with multifocal mucosal lichen planus. J Oral Pathol Med 41(1):86–89
O’Loughlin AJ, Woffindale CA, Wood JAM (2012) Exosomes and the emerging field of exosome-based gene therapy. Curr Gene Ther 12(4):262–274
Ogawa Y, Kanai-Azuma M, Akimoto Y, Kawakami H, Yanoshita R (2008) Exosome-like vesicles with dipeptidyl peptidase IV in human saliva. Biol Pharm Bull 31(6):1059–1062
Ogawa Y, Taketomi Y, Murakami M, Tsujimoto M, Yanoshita R (2013) Small RNA transcriptomes of two types of exosomes in human whole saliva determined by next generation sequencing. Biol Pharm Bull 36(1):66–75
Ogawa Y, Tsujimoto M, Yanoshita R (2016) Next-generation sequencing of protein-coding and long non-protein-coding RNAs in two types of exosomes derived from human whole saliva. Biol Pharm Bull 39(9):1496–1507
Okami K, Imate Y, Hashimoto Y, Kamada T, Takahashi M (2002) Molecular detection of cancer cells in saliva from oral and pharyngeal cancer patients. Tokai J Exp Clin Med 27(3):85–89
Ovchinnikov DA, Cooper MA, Pandit P, Coman WB, Cooper-White JJ, Keith P, Wolvetang EJ, Slowey PD, Punyadeera C (2012) Tumor-suppressor gene promoter Hypermethylation in saliva of head and neck cancer patients. Transl Oncol 5(5):321–326. Epub 2012 Oct 1
Ovchinnikov DA, Wan Y, Coman WB, Pandit P, Cooper-White JJ, Herman JG, Punyadeera C (2014) DNA methylation at the novel CpG sites in the promoter of MED15/PCQAP gene as a biomarker for head and neck cancers. Biomark Insights 9:53–60. https://doi.org/10.4137/BMI.S16199
Panneer Selvam N, Sadaksharam J (2015) Salivary interleukin-6 in the detection of oral cancer and precancer. Asia Pac J Clin Oncol 11(3):236–241
Park NJ, Zhou H, Elashoff D, Henson BS, Kastratovic DA, Abemayor E, Wong DT (2009) Salivary microRNA: discovery, characterization, and clinical utility for oral cancer detection. Clin Cancer Res 15(17):5473–5477
Patel S, Metgud R (2015) Estimation of salivary lactate dehydrogenase in oral leukoplakia and oral squamous cell carcinoma: a biochemical study. J Cancer Res Ther 11(1):119–123
Pattani KM, Zhang Z, Demokan S, Glazer C, Loyo M, Goodman S, Sidransky D, Bermudez F, Jean-Charles G, McCaffrey T, Padhya T, Phelan J, Spivakovsky S, Bowne HY, Goldberg JD, Rolnitzky L, Robbins M, Kerr AR, Sirois D, Califano JA (2010) Endothelin receptor type B gene promoter hypermethylation in salivary rinses is independently associated with risk of oral cavity cancer and premalignancy. Cancer Prev Res (Phila) 3(9):1093–1103
Peinado H, Lavotshkin S, Lyden D (2011) The secreted factors responsible for pre-metastatic niche formation: old sayings and new thoughts. Semin Cancer Biol 21:139–146
Peinado H, Alečković M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, García-Santos G, Ghajar CM (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18(6):883–891
Piyathilake CJ, Bell WC, Jones J, Henao OL, Heimburger DC, Niveleau A, Grizzle WE (2005) Patterns of global DNA and histone methylation appear to be similar in normal, dysplastic and neoplastic oral epithelium of humans. Dis Markers 21(3):147–151
Properzi F, Logozzi M, Fais S (2013) Exosomes: the future of biomarkers in medicine. Biomarkers 7(5):769–778
Punyani SR, Sathawane RS (2013) Salivary level of interleukin-8 in oral precancer and oral squamous cell carcinoma. Clin Oral Investig 17(2):517–524
Pushalkar S, Mane SP, Ji X, Li Y, Evans C, Crasta OR, Morse D, Meagher R, Singh A, Saxena D (2011) Microbial diversity in saliva of oral squamous cell carcinoma. FEMS Immunol Med Microbiol 61(3):269–277
Puttipanyalears C, Subbalekha K, Mutirangura A, Kitkumthorn N (2013) Alu hypomethylation in smoke-exposed epithelia and oral squamous carcinoma. Asian Pac J Cancer Prev 14(9):5495–5501
Record M, Carayon K, Poirot M, Silvente-Poirot S (2014) Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies. Biochim Biophys Acta 1841(1):108–120
Rettori MM, de Carvalho AC, Bomfim Longo AL, de Oliveira CZ, Kowalski LP, Carvalho AL, Vettore AL (2013a) Prognostic significance of TIMP3 hypermethylation in post-treatment salivary rinse from head and neck squamous cell carcinoma patients. Carcinogenesis 34(1):20–27
Rettori MM, de Carvalho AC, Longo AL, de Oliveira CZ, Kowalski LP, Carvalho AL, Vettore AL (2013b) TIMP3 and CCNA1 hypermethylation in HNSCC is associated with an increased incidence of second primary tumors. J Transl Med 11:316
Rhodus NL, Cheng B, Myers S, Bowles W, Ho V, Ondrey F (2005) A comparison of the pro-inflammatory, NF-kappab-dependent cytokines: TNF-alpha, IL-1-alpha, IL-6, and IL-8 in different oral fluids from oral lichen planus patients. Clin Immunol (Orlando, Fla) 114(3):278–283
Rhodus NL, Cheng B, Bowles W, Myers S, Miller L, Ondrey F (2006) Proinflammatory cytokine levels in saliva before and after treatment of (erosive) oral lichen planus with dexamethasone. Oral Dis 12(2):112–116
Righini CA, de Fraipont F, Timsit JF, Faure C, Brambilla E, Reyt E, Favrot MC (2007) Tumor-specific methylation in saliva: a promising biomarker for early detection of head and neck cancer recurrence. Clin Cancer Res 13:1179–1185
Robinson PN, Mickelson AR (2006) Early diagnosis of oral cavity cancers. Otolaryngol Clin N Am 39(2):295–306
Rosas SL, Koch W, da Costa Carvalho MG, Wu L, Califano J, Westra W, Jen J, Sidransky D (2001) Promoter hypermethylation patterns of p16, O6-methylguanine-DNA-methyltransferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients. Cancer Res 61:939–942
Saito Y, Takazawa H, Uzawa K, Tanzawa H, Sato K (1998) Reduced expression of E-cadherin in oral squamous cell carcinoma: relationship with DNA methylation of 5′ CpG island. Int J Oncol 12(2):293–298
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 60:892–895
Sansone P, Savini C, Kurelac I, Chang Q, Amato LB, Strillacci A, Stepanova A, Iommarini L, Mastroleo C, Daly L, Galkin A, Thakur BK, Soplop N, Uryu K, Hoshino A, Norton L, Bonafé M, Cricca M, Gasparre G, Lyden D, Bromberg J (2017) Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer. Proc Natl Acad Sci U S A 114(43):E9075
Schafer CA, Schafer JJ, Yakob M, Lima P, Camargo P, Wong DT (2014) Saliva diagnostics: utilizing oral fluids to determine health status. Monogr Oral Sci 24:88–98
Schnipper LE, Davidson NE, Wollins DS, Tyne C, Blayney DW, Blum D, American Society of Clinical Oncology, Null (2015). American society of clinical oncology statement: a conceptual framework to assess the value of cancer treatment options. J Clin Oncol Off J Am Soc Clin Oncol 33(23):2563–2577
Schulz BL, Cooper-White J, Punyadeera CK (2013) Saliva proteome research: current status and future outlook. Crit Rev Biotechnol 33(3):246–259
Schussel J, Zhou XC, Zhang Z, Pattani K, Bermudez F, Jean-Charles G, McCaffrey T, Padhya T, Phelan J, Spivakovsky S, Brait M, Li R, Bowne HY, Goldberg JD, Rolnitzky L, Robbins M, Kerr AR, Sirois D, Califano JA (2013) EDNRB and DCC salivary rinse hypermethylation has a similar performance as expert clinical examination in discrimination of oral cancer/dysplasia versus benign lesions. Clin Cancer Res 19(12):3268–3275
Shahidi M, Jafari S, Barati M, Mahdipour M, Gholami MS (2017) Predictive value of salivary microrna-320a, vascular endothelial growth factor receptor 2, CRP and IL-6 in Oral lichen planus progression. Inflammopharmacology
Shapiro B, Chakrabarty M, Cohn EM, Leon SA (1983) Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease. Cancer 51(11):2116–2120
Sharma M, Bairy I, Pai K, Satyamoorthy K, Prasad S, Berkovitz B, Radhakrishnan R (2011) Salivary IL-6 levels in oral leucoplakia with dysplasia and its clinical relevance to tobacco habits and periodontitis. Clin Oral Investig 15(5):705–714
Shaw RJ, Liloglou T, Rogers SN, Brown JS, Vaughan ED, Lowe D, Field JK, Risk JM (2006) Promoter methylation of P16, RARbeta, E-cadherin, cyclin A1 and cytoglobin in oral cancer: quantitative evaluation using pyrosequencing. Br J Cancer 94:561–568
Shetty SR, Chadha R, Babu S, Kumari S, Bhat S, Achalli S (2012) Salivary lactate dehydrogenase levels in oral leucoplakia and oral squamous cell carcinoma: a biochemical and clinicopathological study. J Cancer Res Ther 8(Suppl 1):123
Shetty SR, Babu S, Kumari S, Shetty P, Hegde S, Karikal A (2015) Status of trace elements in saliva of oral precancer and oral cancer patients. J Cancer Res Ther 11(1):146–149
Shigeyama H, Wang T, Ichinose M, Ansai T, Lee SW (2018) Identification of volatile metabolites in human saliva from patients with oral squamous cell carcinoma via zeolite-based thin-film microextraction coupled with GC-MS. J Chromatogr B Analyt Technol Biomed Life Sci 1104:49–58
Shiiki N, Tokuyama S, Sato C, Kondo Y, Saruta J, Mori Y, Shiiki K, Miyoshi Y, Tsukinoki K (2011) Association between saliva PSA and serum PSA in conditions with prostate adenocarcinoma. Biomarkers 16(6):498–503
Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67(1):7–30
Simkin M, Abdalla M, El-Mogy M, Haj-Ahmad Y (2012) Differences in the quantity of DNA found in the urine and saliva of smokers versus nonsmokers: implications for the timing of epigenetic events. Epigenomics 4(3):343–352
Singh NN, Peer A, Nair S, Chaturvedi RK (2016) Epigenetics: a possible answer to the undeciphered etiopathogenesis and behavior of oral lesions. J Oral Maxillof Pathol: JOMFP 20(1):122–128
Smith AK, Kilaru V, Klengel T, Mercer KB, Bradley B, Conneely KN, Binder EB (2015) DNA extracted from saliva for methylation studies of psychiatric traits: evidence tissue specificity and relatedness to brain. American journal of medical genetics. Part B, neuropsychiatric genetics: the official publication of the international society of. Psychiatr Genet 168B(1):36–44
Smith RA, Andrews KS, Brooks D, Fedewa SA, Manassaram-Baptiste D, Saslow D et al (2017) Cancer screening in the United States, 2017: a review of current American cancer society guidelines and current issues in cancer screening. CA Cancer J Clin 67(2):100–121
Spielmann N, Wong DT (2011) Saliva: diagnostics and therapeutic perspectives. Oral Dis 17(4):345–354
Steinmann K, Sandner A, Schagdarsurengin U, Dammann RH (2009) Frequent promoter hypermethylation of tumor-related genes in head and neck squamous cell carcinoma. Oncol Rep 22(6):1519–1526
Stewart CM, Tsui DWY (2018) Circulating cell-free DNA for non-invasive cancer management. Cancer Genet 228–229:169–179
Streckfus C, Bigler L, Dellinger T, Dai X, Kingman A, Thigpen JT (2000) The presence of soluble c-erbB-2 in saliva and serum among women with breast carcinoma: a preliminary study. Clin Cancer Res 6(6):2363–2370
Su PF, Huang WL, Wu HT, Wu CH, Liu TY, Kao SY (2010) p16(INK4A) promoter hypermethylation is associated with invasiveness and prognosis of oral squamous cell carcinoma in an age-dependent manner. Oral Oncol 46(10):734–739
Tajmul M, Parween F, Singh L, Mathur SR, Sharma JB, Kumar S, Sharma DN, Yadav S (2018) Identification and validation of salivary proteomic signatures for non-invasive detection of ovarian cancer. Int J Biol Macromol 108:503–514
Tawfik HM, El-Maqsoud NM, Hak BH, El-Sherbiny YM (2011) Head and neck squamous cell carcinoma: mismatch repair immunohistochemistry and promoter hypermethylation of hMLH1 gene. Am J Otolaryngol 32(6):528–536
Tian F, Yip SP, Kwong DL, Lin Z, Yang Z, Wu VW (2013) Promoter hypermethylation of tumor suppressor genes in serum as potential biomarker for the diagnosis of nasopharyngeal carcinoma. Cancer Epidemiol 37(5):708–713
Tiziani S, Lopes V, Gunther UL (2009) Early stage diagnosis of oral cancer using 1H NMR-based metabolomics. Neoplasia (New York, NY) 11(3): 269–276, 4p following 269
Tkach M, Théry C (2016) Communication by extracellular vesicles: where we are and where we need to go. Cell 164(6):1226–1232
Tong JH, Tsang RK, Lo KW, Woo JK, Kwong J, Chan MW, Chang AR, van Hasselt CA, Huang DP, To KF (2002) Quantitative Epstein-Barr virus DNA analysis and detection of gene promoter hypermethylation in nasopharyngeal (NP) brushing samples from patients with NP carcinoma. Clin Cancer Res 8:2612–2619
Topkas E, Keith P, Dimeski G, Cooper-White J, Punyadeera C (2012) Evaluation of saliva collection devices for the analysis of proteins. Clinica Chimica Acta; International Journal of Clinical Chemistry 413(13–14):1066–1070
Tvarijonaviciute A, Aznar-Cayuela C, Rubio CP, Ceron JJ, Lopez-Jornet P (2017) Evaluation of salivary oxidate stress biomarkers, nitric oxide and C-reactive protein in patients with oral lichen planus and burning mouth syndrome. J Oral Pathol Med 46(5):387–392
Tvarijonaviciute A, Aznar-Cayuela C, Rubio CP, Tecles F, Ceron JJ, Lopez-Jornet P (2018) Salivary antioxidant status in patients with Oral lichen planus: correlation with clinical signs and evolution during treatment with Chamaemelum nobile. Biomed Res Int 2018:5187549
van der Waal I (2014 July 01) Oral potentially malignant disorders: is malignant transformation predictable and preventable? Med Oral Patol Oral Cir Bucal 19(4):386
Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007a) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659
Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007b) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654
Van Ginkel JH, Slieker FJB, de Bree R, van Es RJJ, Van Cann EM, Willems SM (2017) Cell-free nucleic acids in body fluids as biomarkers for the prediction and early detection of recurrent head and neck cancer: a systematic review of the literature. Oral Oncol 75:8–15
Vento S, Tanko MN (2009) The bacterium that could cause cancer. Lancet Oncology 10(5):528–2045(09). 70038-5
Viet CT, Schmidt BL (2008) Methylation array analysis of preoperative and postoperative saliva DNA in oral cancer patients. Cancer Epidemiol Biomark Prev 17(12):3603–3611
Wang Q, Gao P, Cheng F, Wang X, Duan Y (2014) Measurement of salivary metabolite biomarkers for early monitoring of oral cancer with ultra performance liquid chromatography-mass spectrometry. Talanta 119:299–305
Wang Q, Yu Q, Lin Q, Duan Y (2015a) Emerging salivary biomarkers by mass spectrometry. Clinicachimica Acta Int J Clin Chem 438:214–221
Wang Y, Springer S, Mulvey CL, Silliman N, Schaefer J, Sausen M, James N, Rettig EM, Guo T, Pickering CR, Bishop JA, Chung CH, Califano JA, Eisele DW, Fakhry C, Gourin CG, Ha PK, Kang H, Kiess A, Koch WM, Myers JN, Quon H, Richmon JD, Sidransky D, Tufano RP, Westra WH, Bettegowda C, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B, Agrawal N (2015b) Detection of somatic mutations and HPV in the saliva and plasma of patients with head and neck squamous cell carcinomas. Sci Transl Med 7(293):293ra104
Warnakulasuriya S, Johnson NW, Van Der Waal I (2007) Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 36(10):575–580
Warnakulasuriya S, Kovacevic T, Madden P, Coupland VH, Sperandio M, Odell E, Moller H (2011) Factors predicting malignant transformation in oral potentially malignant disorders among patients accrued over a 10-year period in south East England. J Oral Pathol Med 40(9):677–683
Weber A, Wittekind C, Tannapfel A (2003) Genetic and epigenetic alterations of 9p21 gene products in benign and malignant tumors of the head and neck. Pathol Res Pract 199:391–397
Webber J, Steadman R, Mason MD, Tabi Z, Clayton A (2010) Cancer exosomes trigger fibroblast to myofibroblast differentiation. Cancer Res 70(23):9621–9630
Wei J, Xie G, Zhou Z, Shi P, Qiu Y, Zheng X, Chen T, Su M, Zhao A, Jia W (2011) Salivary metabolite signatures of oral cancer and leucoplakia. Int J Cancer 129(9):2207–2217
Weiss D, Basel T, Sachse F, Braeuninger A, Rudack C (2011) Promoter methylation of cyclin A1 is associated with human papillomavirus 16 induced head and neck squamous cell carcinoma independently of p53 mutation. Mol Carcinog 50(9):680–688
Wilhelm M, Schlegl J, Hahne H, Gholami AM, Lieberenz M, Savitski MM, Ziegler E, Butzmann L, Gessulat S, Marx H, Mathieson T, Lemeer S, Schnatbaum K, Reimer U, Wenschuh H, Mollenhauer M, Slotta-Huspenina J, Boese JH, Bantscheff M, Gerstmair A, Faerber F, Kuster B (2014) Mass-spectrometry-based draft of the human proteome. Nature 509(7502):582–587
Wong TS, Man MW, Lam AK, Wei WI, Kwong YL, Yuen AP (2003) The study of p16 and p15 gene methylation in head and neck squamous cell carcinoma and their quantitative evaluation in plasma by real-time PCR. Eur J Cancer 39:1881–1887
Wu CC, Chu HW, Hsu CW, Chang KP, Liu HP (2015) Saliva proteome profiling reveals potential salivary biomarkers for detection of oral cavity squamous cell carcinoma. Proteomics 15(19):3394–3404
Xiao H, Zhang L, Zhou H, Lee JM, Garon EB, Wong DTW (2012) Proteomic analysis of human saliva from lung Cancer patients using two-dimensional difference gel electrophoresis and mass spectrometry. Mol Cell Proteomics 11(2):M111.012112
Xie H, Onsongo G, Popko J, de Jong EP, Cao J, Carlis JV, Griffin RJ, Rhodus NL, Griffin TJ (2008) Proteomics analysis of cells in whole saliva from oral cancer patients via value-added three-dimensional peptide fractionation and tandem mass spectrometry. Mol Cell Proteomics 7(3):486–498
Yan SK, Wei BJ, Lin ZY, Yang Y, Zhou ZT, Zhang WD (2008) A metabonomic approach to the diagnosis of oral squamous cell carcinoma, oral lichen planus and oral leucoplakia. Oral Oncol 44(5):477–483
Yang, Y., Li, Y.X., Yang, X., Jiang, L., Zhou, Z.J. And Zhu, Y.Q., 2013. Progress risk assessment of oral premalignant lesions with saliva miRNA analysis. BMC Cancer, 13, pp. 129
Yang Y, Rhodus NL, Ondrey FG, Wuertz BR, Chen X, Zhu Y, Griffin TJ (2014) Quantitative proteomic analysis of oral brush biopsies identifies secretory leukocyte protease inhibitor as a promising, mechanism-based oral cancer biomarker. PLoS One 9(4):E95389
You Y, Yang W, Wang Z, Zhu H, Li H, Lin C, Ran Y (2013) Promoter hypermethylation contributes to the frequent suppression of the CDK10 gene in human nasopharyngeal carcinomas. Cell Oncol (Dordr) 36(4):323–331
Yu JS, Chen YT, Chiang WF, Hsiao YC, Chu LJ, See LC, Wu CS, Tu HT, Chen HW, Chen CC, Liao WC, Chang YT, Wu CC, Lin CY, Liu SY, Chiou ST, Chia SL, Chang KP, Chien CY, Chang SW, Chang CJ, Young JD, Pao CC, Chang YS, Hartwell LH (2016) Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan. Proc Natl Acad Sci USA 113(41):11549–11554
Zahran F, Ghalwash D, Shaker O, Al-Johani K, Scully C (2015) Salivary micrornas in oral cancer. Oral Dis 21(6):739–747
Zhang Z, Sun D, Hutajulu SH, Nawaz I, Nguyen Van D, Huang G, Haryana SM, Middeldorp JM, Ernberg I, Hu LF (2012a) Development of a non-invasive method, multiplex methylation specific PCR (MMSP), for early diagnosis of nasopharyngeal carcinoma. PLoS One 7(11):e45908
Zhang L, Xiao H, Zhou H, Santiago S, Lee JM, Garon EB, Yang J, Brinkmann O, Yan X, Akin D, Chia D, Elashoff D, Park NH, Wong DTW (2012b) Development of transcriptomic biomarker signature in human saliva to detect lung cancer. Cell Mol Life Sci 69(19):3341–3350
Zhou C, Shen Z, Ye D, Li Q, Deng H, Liu H, Li J (2018) The association and clinical significance of CDKN2A promoter methylation in head and neck squamous cell carcinoma: a meta-analysis. Cell Physiol Biochem 50(3):868–882
Zlotogorski-Hurvitz A, Dayan D, Chaushu G, Salo T, Vered M (2016) Morphological and molecular features of oral fluid-derived exosomes: oral cancer patients versus healthy individuals. J Cancer Res Clin Oncol 142(1):101–110
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Pérez-Sayáns, M., Chamorro-Petronacci, C.M., Gándara-Vila, P., Lorenzo-Pouso, A.I. (2020). Salivary Markers in Systemic and Oral Cancer. In: Tvarijonaviciute, A., Martínez-Subiela, S., López-Jornet, P., Lamy, E. (eds) Saliva in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-37681-9_12
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