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http://dx.doi.org/10.11620/IJOB.2018.43.1.013

Changes in Oral Microbiota in Patients Receiving Radical Concurrent Chemoradiotherapy for The Head and Neck Squamous Cell Carcinoma  

Kim, Jin Ho (Department of Radiation Oncology, Seoul National University Hospital)
Choi, Yoon Hee (Department of Hematology-Oncology, Dongnam Institute of Radiological and Medical Sciences)
An, Soo-Youn (Department of Otolaryngology-Head and Neck Surgery, Dongnam Institute of Radiological and Medical Sciences)
Son, Hee Young (Department of Otolaryngology-Head and Neck Surgery, Dongnam Institute of Radiological and Medical Sciences)
Choi, Chulwon (Department of Radiation Oncology, Dongnam Institute of Radiological and Medical Sciences)
Kim, Seyeon (Department of Oral Microbiology, School of Dentistry, Pusan National University)
Chung, Jin (Department of Oral Microbiology, School of Dentistry, Pusan National University)
Na, Hee Sam (Department of Oral Microbiology, School of Dentistry, Pusan National University)
Publication Information
International Journal of Oral Biology / v.43, no.1, 2018 , pp. 13-21 More about this Journal
Abstract
Radiotherapy (RT) is a mainstay in the treatment of head and neck squamous cell carcinoma (HNSCC). For locally advanced HCSCC, concurrent chemoradiotherapy (CCRT) benefits HCSCC patients in terms of better survival and loco-regional control. In this study, we evaluated changes in oral microbiota in patients, who received CCRT for head and neck cancer. Oral rinsed samples were weekly collected before and during CCRT and at 4 weeks following treatment from HNSCC patients, who had received 70 Gy of radiation delivered to the primary sites for over 7 weeks and concurrent chemotherapy. Oral microbiota changes in three patients were analyzed by next-generation sequencing using 16S rRNA 454 pyrosequencing. On an average, 15,000 partial 16S rRNA gene sequences were obtained from each sample. All sequences fell into 11 different bacterial phyla. During early CCRT, the microbial diversity gradually decreased. In a patient, who did not receive any antibiotics during the CCRT, Firmicutes and Proteobacteria were the most abundant phylum. During the early CCRT, proteobacteria gradually decreased while Firmicutes increased. During the late CCRT, firmicutes gradually decreased while Bacteroides and Fusobacteria increased. In all the patients, yellow complex showed a gradual decrease, while orange and red complex showed a gradual increase during the CCRT. At 4 weeks after CCRT, the recovery of oral microbiota diversity was limited. During CCRT, there was a gradual increase in major periodontopathogens in association with the deterioration of the oral hygiene. Henceforth, it is proposed that understanding oral microbiota shift should provide better information for the development of effective oral care programs for patients receiving CCRT for HNSCC.
Keywords
Pyrosequencing; Oral microbiota; Head and neck squamous cell carcinoma; Concurrent chemoradiotherapy;
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1 Jung KW, Won YJ, Kong HJ, Oh CM, Lee DH, Lee JS. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2011. Cancer Res Treat 2014; 46:109-123. doi:10.4143/crt.2014.46.2.109.   DOI
2 Elting LS, Keefe DM, Sonis ST, Garden AS, Spijkervet FK, Barasch A, Tishler RB, Canty TP, Kudrimoti MK, Vera-Llonch M. Patient-reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy: demonstration of increased frequency, severity, resistance to palliation, and impact on quality of life. Cancer 2008; 113:2704-2713. doi:10.1002/cncr.23898.   DOI
3 Duarte VM, Liu YF, Rafizadeh S, Tajima T, Nabili V, Wang MB. Comparison of dental health of patients with head and neck cancer receiving IMRT vs conventional radiation. Otolaryngology--head and neck surgery. Otolaryngol Head Neck Surgery 2014; 150:81-86. doi:10.1177/0194599813509586.   DOI
4 Pignon JP, le Maitre A, Maillard E, Bourhis J, Group M-NC. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009; 92:4-14. doi: 10.1016/j.radonc.2009.04.014.   DOI
5 Adelstein DJ, Saxton JP, Lavertu P, Tuason L, Wood BG, Wanamaker JR, Eliachar I, Strome M, Van Kirk MA. A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results. Head Neck 1997; 19:567-575.   DOI
6 Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003; 349: 2091-2098. doi: 10.1056/NEJMoa031317.   DOI
7 Calais G, Alfonsi M, Bardet E, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Oudinot P, Bertrand P. Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst 1999; 91:2081-2086.   DOI
8 Nutting CM, Morden JP, Harrington KJ, Urbano TG, Bhide SA, Clark C, Miles EA, Miah AB, Newbold K, Tanay M, Adab F, Jefferies SJ, Scrase C, Yap BK, A'Hern RP, Sydenham MA, Emson M, Hall E, group Ptm. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol 2011; 12:127-136. doi: 10.1016/S1470-2045(10)70290-4.   DOI
9 Kam MK, Leung SF, Zee B, Chau RM, Suen JJ, Mo F, Lai M, Ho R, Cheung KY, Yu BK, Chiu SK, Choi PH, Teo PM, Kwan WH, Chan AT. Prospective randomized study of intensitymodulated radiotherapy on salivary gland function in earlystage nasopharyngeal carcinoma patients. J Clin Oncol 2007;25:4873-4879. doi:10.1200/JCO.2007.11.5501.   DOI
10 Gupta T, Agarwal J, Jain S, Phurailatpam R, Kannan S, Ghosh-Laskar S, Murthy V, Budrukkar A, Dinshaw K, Prabhash K, Chaturvedi P, D'Cruz A. Three-dimensional conformal radiotherapy (3D-CRT) versus intensity modulated radiation therapy (IMRT) in squamous cell carcinoma of the head and neck: a randomized controlled trial. Radiother Oncol 2012; 104:343-348. doi:10.1016/j.radonc.2012.07.001.   DOI
11 Sbordone L, Bortolaia C. Oral microbial biofilms and plaquerelated diseases: microbial communities and their role in the shift from oral health to disease. Clin Oral Investig 2003;7:181-188. doi:10.1007/s00784-003-0236-1.   DOI
12 Nonzee V, Manopatanakul S, Khovidhunkit SO. Xerostomia, hyposalivation and oral microbiota in patients using antihypertensive medications. J Med Assoc Thai 2012;95:96-104.
13 Almstah IA, Wikstrom M, Stenberg I, Jakobsson A, Fagerberg-Mohlin B. Oral microbiota associated with hyposalivation of different origins. Oral Microbiol Immunol 2003; 18:1-8.   DOI
14 Tong HC, Gao XJ, Dong XZ. Non-mutans streptococci in patients receiving radiotherapy in the head and neck area. Caries Res 2003; 37:261-266.   DOI
15 Sonis ST. The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy. Crit Rev Oral Biol Med 2002; 13:380-389.   DOI
16 Shade A, Handelsman J. Beyond the Venn diagram: the hunt for a core microbiome. Environ Microbiol 2012; 14:4-12. doi:10.1111/j.1462-2920.2011.02585.x.   DOI
17 Langfeldt D, Neulinger SC, Heuer W, Staufenbiel I, Kunzel S, Baines JF, Eberhard J, Schmitz RA. Composition of Microbial Oral Biofilms during Maturation in Young Healthy Adults. PLoS One 2014; 9:e87449. doi:10.1371/journal.pone.0087449.   DOI
18 Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature 2007; 449:804-810. doi:10.1038/nature06244.   DOI
19 Saber MH, Schwarzberg K, Alonaizan FA, Kelley ST, Sedghizadeh PP, Furlan M, Levy TA, Simon JH, Slots J. Bacterial flora of dental periradicular lesions analyzed by the 454-pyrosequencing technology. J Endod 2012; 38:1484-1488. doi: 10.1016/j.joen.2012.06.037.   DOI
20 Na HS, Kim S, Choi YH, Lee J-Y, Chung J. Oral Microbiota comparison between Healthy volunteer, Periodontitis patients and Oral cancer patients. Int J Oral Biol 2013; 38: 181-188.   DOI
21 Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL, Jr. Microbial complexes in subgingival plaque. J Clin Periodontol 1998; 25:134-144.   DOI
22 Jensen SB, Pedersen AM, Vissink A, Andersen E, Brown CG, Davies AN, Dutilh J, Fulton JS, Jankovic L, Lopes NN, Mello AL, Muniz LV, Murdoch-Kinch CA, Nair RG, Napenas JJ, Nogueira-Rodrigues A, Saunders D, Stirling B, von Bultzingslowen I, Weikel DS, Elting LS, Spijkervet FK, Brennan MT. A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life. Support Care Cancer 2010; 18:1039-1060. doi:10.1007/s00520-010-0827-8.   DOI
23 Hu YJ, Shao ZY, Wang Q, Jiang YT, Ma R, Tang ZS, Liu Z, Liang JP, Huang ZW. Exploring the dynamic core microbiome of plaque microbiota during head-and-neck radiotherapy using pyrosequencing. PLoS One 2013;8:e56343. doi:10.1371/journal.pone.0056343.   DOI
24 Mager DL, Haffajee AD, Devlin PM, Norris CM, Posner MR, Goodson JM. 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 2005; 3:27. doi:10.1186/1479-5876-3-27.   DOI
25 Khaw A, Logan R, Keefe D, Bartold M. Radiation-induced oral mucositis and periodontitis - proposal for an interrelationship. Oral Dis 2014; 20: e7-18. doi:10.1111/odi.12199.   DOI
26 Whitmore SE, Lamont RJ. Oral bacteria and cancer. PLoS pathogens 2014; 10:e1003933. doi: 10.1371/journal.ppat.1003933.   DOI
27 Masschalck B, Michiels CW. Antimicrobial properties of lysozyme in relation to foodborne vegetative bacteria. Crit Rev Microbiol 2003; 29:191-214. doi: 10.1080/713610448.   DOI
28 Thomas EL, Milligan TW, Joyner RE, Jefferson MM. Antibacterial activity of hydrogen peroxide and the lactoperoxidase-hydrogen peroxide-thiocyanate system against oral streptococci. Infection and immunity 1994;62:529-535.
29 Bochkov IA. (Nasopharyngeal microorganisms--antagonists of meningococci). Zh Mikrobiol Epideminol Immunobiol 1975:81-86.
30 Bochkov IA, Semina NA. (Role of Streptococcus salivarius in maintaining the ecologic balance of the human nasopharynx). Zh Mikrobiol Epidemiol Immunobiol 1981:38-41.
31 Palmer RJ, Jr., Diaz PI, Kolenbrander PE. Rapid succession within the Veillonella population of a developing human oral biofilm in situ. J Bacteriol 2006; 188:4117-4124. doi: 10.1128/jb.01958-05.   DOI
32 Liu B, Faller LL, Klitgord N, Mazumdar V, Ghodsi M, Sommer DD, Gibbons TR, Treangen TJ, Chang YC, Li S, Stine OC, Hasturk H, Kasif S, Segre D, Pop M, Amar S. Deep sequencing of the oral microbiome reveals signatures of periodontal disease. PLoS One 2012; 7:e37919. doi: 10.1371/journal.pone.0037919.   DOI
33 Weinstein AJ. The cephalosporins: activity and clinical use. Drugs 1980; 20:137-154.   DOI
34 Ammajan RR, Joseph R, Rajeev R, Choudhary K, Vidhyadharan K. Assessment of periodontal changes in patients undergoing radiotherapy for head and neck malignancy: A hospital-based study. J Cancer Res Ther 2013;9:630-637. doi: 10.4103/0973-1482.126461.   DOI
35 Leung WK, Jin LJ, Samaranayake LP, Chiu GK. Subgingival microbiota of shallow periodontal pockets in individuals after head and neck irradiation. Oral Microbiol Immunol 1998; 13:1-10.   DOI
36 Socransky SS, Haffajee AD. Periodontal microbial ecology. Periodontol 2000 2005; 38:135-187.
37 Lazarevic V, Whiteson K, Hernandez D, Francois P, Schrenzel J. Study of inter- and intra-individual variations in the salivary microbiota. BMC Genomics 2010; 11:523. doi: 10.1186/1471-2164-11-523.   DOI
38 Costello EK, Lauber CL, Hamady M, Fierer N, Gordon JI, Knight R. Bacterial community variation in human body habitats across space and time. Science 2009; 326:1694-1697. doi:10.1126/science.1177486.   DOI