Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2024, Vol. 38 ›› Issue (6): 39-45.doi: 10.6040/j.issn.1673-3770.0.2023.010

• Research Progress • Previous Articles     Next Articles

Exploration of the relationship between laryngopharyngeal reflux and recurrent respiratory papilloma and its mechanism

ZHAO Jianing, CUI Yuanxin, WANG Dan, ZHAO Ming   

  1. Department of Otorhinolaryngology & Head and Neck Surgery, The Second Hospital of Jilin University, Changchun 130022, Jilin, China
  • Published:2024-12-13

Abstract: Laryngopharyngeal reflux(LPR)has a non-negligible role in the development of laryngeal tumors as an independent risk factor. Recurrent respiratory papillomatosis(RRP)is a disease with a very high recurrence rate, mostly in the larynx, which is benign but can be cancerous. The main treatment remains surgery, and the application of drugs, such as interferon and cidofovir, can be used as adjuvant therapy. Some studies have found that anti-reflux treatment also controls its development, and several studies have shown that LPR may be a risk factor for recurrent respiratory papillomatosis. We review the relevant literature at home and abroad that introduce the current research progress in LPR and RRP and discuss the possible relationship between LPR and RRP and the possible role of LPR in the occurrence, development, and malignant transformation of RRP to provide a theoretical basis for the next in-depth exploration of the specific mechanism and provide clinicians with new ideas for the diagnosis and treatment of RRP.

Key words: Laryngopharyngeal reflux, Recurrent respiratory papillomatosis, Human papillomavirus, Pepsin

CLC Number: 

  • R766.5
[1] Ivancic R, Iqbal H, DeSilva B, et al. Current and future management of recurrent respiratory papillomatosis[J]. Laryngoscope Investig Otolaryngol, 2018,3(1):22-34. doi:10.1002/lio2.132
[2] Gluvaji c D, Šereg-Bahar M, Jerin A, et al. The Impact of Laryngopharyngeal Reflux on Occurrence and Clinical Course of Recurrent Respiratory Papillomatosis[J]. Laryngoscope, 2022,132(3):619-625. doi:10.1002/lary.29793
[3] Aaltonen LM, Peltomaa J, Rihkanen H. Prognostic value of clinical findings in histologically verified adult-onset laryngeal papillomas[J]. Eur Arch Otorhinolaryngol, 1997,254(5):219-222. doi:10.1007/BF00874092
[4] Buchinsky FJ, Ruszkay N, Valentino W, et al. In RRP, serologic response to HPV is frequently absent and slow to develop[J]. PLoS One, 2020,15(3):e230106. doi:10.1371/journal.pone.0230106
[5] Formánek M, Komínek P, Jan catová D, et al. Laryngopharyngeal Reflux Is a Potential Risk Factor for Juvenile-Onset Recurrent Respiratory Papillomatosis[J]. Biomed Res Int, 2019:1463896. doi:10.1111/coa.12779
[6] Formánek M, Jan catová D, Komínek P, et al. Laryngopharyngeal reflux and herpes simplex virus type 2 are possible risk factors for adult-onset recurrent respiratory papillomatosis(prospective case-control study)[J]. Clin Otolaryngol, 2017,42(3):597-601. doi:10.1155/2019/1463896
[7] Lechien JR, Saussez S, Nacci A, et al. Association between laryngopharyngeal reflux and benign vocal folds lesions: A systematic review[J]. Laryngoscope, 2019,129(9):E329-E341. doi:10.1002/lary.27932
[8] Borkowski G, Sommer P, Stark T, et al. Recurrent respiratory papillomatosis associated with gastroesophageal reflux disease in children[J]. Eur Arch Otorhinolaryngol, 1999, 256(7): 370-372.
[9] Holland BW, Koufman JA, Postma GN, et al. Laryngopharyngeal reflux and laryngeal web formation in patients with pediatric recurrent respiratory papillomas[J]. Laryngoscope, 2002,112(11): 1926-1929.
[10] McKenna M, Brodsky L. Extraesophageal acid reflux and recurrent respiratory papilloma in children[J]. Int J Pediatr Otorhinolaryngol, 2005, 69(5): 597-605.
[11] Pignatari SS, Liriano RY, Avelino MA, et al. Gastroesophageal reflux in patients with recurrent laryngeal papillomatosis[J]. Braz J Otorhinolaryngol, 2007,73(2):210-214.
[12] San GM, Helder HM, Lindeman RJ, et al. The association between gastroesophageal reflux disease and recurrent respiratory papillomatosis: A systematic review[J]. Laryngoscope, 2016,126(10):2330-2339. doi:10.1002/lary.25898
[13] Liu D, Qian T, Sun S, et al. Laryngopharyngeal Reflux and Inflammatory Responses in Mucosal Barrier Dysfunction of the Upper Aerodigestive Tract[J]. J Inflamm Res, 2020,13:1291-1304. doi:10.2147/JIR.S282809
[14] 郝梅, 蒋兴旺, 陈浩, 等. 睡眠剥夺大鼠喉上皮细胞屏障功能改变在咽喉反流发病机制中的作用[J]. 听力学及言语疾病杂志, 2022, 30(6): 577-581. doi: 10.3969/j.issn.1006-7299.2022.06.002 HAO Mei, JIANG Xingwang, CHEN Hao, et al. The role of barrier function of laryngeal epithelial cells in the pathogenesis of laryngopharyngeal reflux in sleep deprived rats[J]. Journal of Audiology and Speech Pathology, 2022, 30(6): 577-581.doi: 10.3969/j.issn.1006-7299.2022.06.002
[15] Hunt EB, Sullivan A, Galvin J, et al. Gastric Aspiration and Its Role in Airway Inflammation[J]. Open Respir Med J, 2018,12:1-10. doi:10.2174/1874306401812010083
[16] Wood JM, Hussey DJ, Woods CM, et al. Biomarkers and laryngopharyngeal reflux[J]. J Laryngol Otol, 2011,125(12):1218-1224. doi:10.1017/S0022215111002234
[17] Axford SE, Sharp N, Ross PE, et al. Cell biology of laryngeal epithelial defenses in health and disease: preliminary studies[J]. Ann Otol Rhinol Laryngol, 2001,110(12):1099-1108. doi:10.1177/000348940111001203
[18] Johnston N, Dettmar PW, Lively MO, et al. Effect of pepsin on laryngeal stress protein(Sep70, Sep53, and Hsp70)response: role in laryngopharyngeal reflux disease[J]. Ann Otol Rhinol Laryngol, 2006,115(1):47-58. doi:10.1177/000348940611500108
[19] Arndt O, Johannes A, Zeise K, et al. High-risk HPV types in oral and laryngeal papilloma and leukoplakia[J]. Laryngorhinootologie, 1997,76(3):142-149. doi:10.1055/s-2007-997403
[20] Doorbar J, Quint W, Banks L, et al. The biology and life-cycle of human papillomaviruses[J]. Vaccine, 2012, 30(5): 55-70. doi:10.1016/j.vaccine.2012.06.083
[21] Doorbar J, Egawa N, Griffin H, et al. Human papillomavirus molecular biology and disease association[J]. Rev Med Virol, 2015, 2(1): 2-23. doi:10.1002/rmv.1822
[22] Zhou C, Tuong ZK, Frazer IH. Papillomavirus Immune Evasion Strategies Target the Infected Cell and the Local Immune System[J]. Front Oncol, 2019,9:682. doi:10.3389/fonc.2019.00682
[23] McBride AA, Oliveira JG, McPhillips MG. Partitioning viral genomes in mitosis: same idea, different targets[J]. Cell Cycle, 2006,5(14):1499-1502. doi:10.4161/cc.5.14.3094
[24] Day PM, Lowy DR, Schiller JT. Heparan sulfate-independent cell binding and infection with furin-precleaved papillomavirus capsids[J]. J Virol, 2008,82(24):12565-12568. doi:10.1128/JVI.01631-08
[25] Joyce JG, Tung JS, Przysiecki CT, et al. The L1 major capsid protein of human papillomavirus type 11 recombinant virus-like particles interacts with heparin and cell-surface glycosaminoglycans on human keratinocytes[J]. J Biol Chem, 1999,274(9):5810-5822. doi:10.1074/jbc.274.9.5810
[26] Ho GY, Bierman R, Beardsley L, et al. Natural history of cervicovaginal papillomavirus infection in young women[J]. N Engl J Med, 1998,338(7):423-428. doi:10.1056/NEJM199802123380703
[27] Neurath MF, Finotto S, Glimcher LH. The role of Th1/Th2 polarization in mucosal immunity[J]. Nat Med, 2002,8(6):567-573. doi:10.1038/nm0602-567
[28] Li SL, Wang W, Zhao J, et al. A review of the risk factors associated with juvenile-onset recurrent respiratory papillomatosis: genetic, immune and clinical aspects[J]. World J Pediatr, 2022,18(2):75-82. doi:10.1007/s12519-021-00496-z
[29] Bonagura VR, Hatam LJ, Rosenthal DW, et al. Recurrent respiratory papillomatosis: a complex defect in immune responsiveness to human papillomavirus-6 and -11[J]. APMIS, 2010,118(6-7):455-470. doi:10.1111/j.1600-0463.2010.02617.x
[30] Rees LE, Pazmany L, Gutowska-Owsiak D, et al. The mucosal immune response to laryngopharyngeal reflux[J]. Am J Respir Crit Care Med, 2008,177(11):1187-1193. doi:10.1164/rccm.200706-895OC
[31] Niu K, Guo C, Teng S, et al. Pepsin promotes laryngopharyngeal neoplasia by modulating signaling pathways to induce cell proliferation[J]. PLoS One, 2020,15(1):e227408. doi:10.1371/journal.pone.0227408
[32] Tilborghs S, Corthouts J, Verhoeven Y, et al. The role of Nuclear Factor-kappa B signaling in human cervical cancer[J]. Crit Rev Oncol Hematol, 2017,120:141-150. doi:10.1016/j.critrevonc.2017.11.001
[33] Mittal D, Gubin MM, Schreiber RD, et al. New insights into cancer immunoediting and its three component phases - elimination, equilibrium and escape[J]. Curr Opin Immunol, 2014,27:16-25. doi:10.1016/j.coi.2014.01.004
[34] Tan JJ, Wang L, Mo TT, et al. Pepsin promotes IL-8 signaling-induced epithelial-mesenchymal transition in laryngeal carcinoma[J]. Cancer Cell Int, 2019,19:64. doi:10.1186/s12935-019-0772-7
[35] 徐志宇, 刘旭, 陈世彩, 等. 咽喉反流性疾病的发病机制及其与耳鼻咽喉疾病相关性研究进展[J]. 听力学及言语疾病杂志, 2022,30(6): 587-590. doi: 10.3969/j.issn.1006-7299.2022.06.004 XU Zhiyu, LIU Xu, CHEN Shicai, et al. Research progress on the pathogenesis of throat reflux disease and its correlation with otorhinolaryngology diseases[J]. Journal of Audiology and Speech Pathology, 2022, 30(6): 587-590. doi: 10.3969/j.issn.1006-7299.2022.06.004
[36] 潘晓菲, 王军, 肖洋, 等. LncRNA CTB-147C22.8对复发性呼吸道乳头状瘤细胞侵袭的影响[J]. 山东大学耳鼻喉眼学报, 2019, 33(4):66-70. doi: 10.6040/j.issn.1673-3770.0.2018.409 PAN Xiaofei, WANG Jun, XIAO Yang, et al. Effects of lncRNA CTB-147C22.8 and mRNA KLK6 on the invasion of recurrent respiratory papilloma cells[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(4): 66-70. doi: 10.6040/j.issn.1673-3770.0.2018.409
[37] 金鑫, 王杨, 冯云鹏, 等. 糖脂代谢关键酶在肿瘤细胞增殖中的作用研究进展[J]. 中国细胞生物学学报, 2022,44(4):682-692. doi:10.11844/cjcb.2022.04.0015 JIN Xin, WANG Yang, FENG Yunpeng, et al. Research progress on the role of key enzymes in glycolipid metabolism in tumor cell proliferation[J]. Chinese Journal of Cell Biology, 2022, 44(4): 682-692. doi:10.11844/cjcb.2022.04.0015
[38] Kocjan BJ, Gale N, Ho cevar B I, et al. Identical human papillomavirus(HPV)genomic variants persist in recurrent respiratory papillomatosis for up to 22 years[J]. J Infect Dis, 2013,207(4):583-587. doi:10.1093/infdis/jis733
[39] Chow LT, Broker TR, Steinberg BM. The natural history of human papillomavirus infections of the mucosal epithelia[J]. APMIS, 2010,118(6-7): 422-449
[40] Carifi M, Napolitano D, Morandi M, et al. Recurrent respiratory papillomatosis: current and future perspectives[J]. Ther Clin Risk Manag, 2015,11:731-738. doi:10.2147/TCRM.S81825
[41] 申宇鹏, 宋琦, 李晓明. 喉癌前病变的病因、分子机制和处理策略[J]. 山东大学耳鼻喉眼学报, 2019, 33(4):25-30. doi: 10.6040/j.issn.1673-3770.1.2019.029 SHEN Yupeng, SONG Qi, LI Xiaoming. Etiology, molecular mechanisms, and treatment strategies of precancerous laryngeal lesions[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(4): 25-30. doi: 10.6040/j.issn.1673-3770.1.2019.029
[42] Taliercio S, Cespedes M, Born H, et al. Adult-onset recurrent respiratory papillomatosis: a review of disease pathogenesis and implications for patient counseling[J]. JAMA Otolaryngol Head Neck Surg, 2015, 141(1): 78-83. doi:10.1001/jamaoto.2014.2826
[43] 王灵娃, 王茹, 房居高. 与喉乳头状瘤恶变进程及预后相关分子标志物研究[J]. 山东大学耳鼻喉眼学报, 2023,37(1):47-55. doi:10.6040/j.issn.1673-3770.0.2022.012 WANG Lingwa, WANG Ru, FANG Jugao. Bioinformatics analysis of key molecular markers for malignant transformation of laryngeal papilloma[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2023, 37(1): 47-55. doi:10.6040/j.issn.1673-3770.0.2022.012
[44] 齐雯雯, 陈鲁秋, 贾涛, 等. 复发性喉乳头状瘤中潜在生物学标志物的筛选及生物信息学分析[J]. 山东大学耳鼻喉眼学报, 2021,35(5):75-84. doi:10.6040/j.issn.1673-3770.0.2021.068 QI Wenwen, CHEN Luqiu, JIA Tao, et al. Potential biomarkers and bioinformatics analysis of differentially expressed genes in recurrent laryngeal papilloma[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2021, 35(5): 75-84. doi:10.6040/j.issn.1673-3770.0.2021.068
[45] Parsel SM, Wu EL, Riley CA, et al. Gastroesophageal and Laryngopharyngeal Reflux Associated With Laryngeal Malignancy: A Systematic Review and Meta-analysis[J]. Clin Gastroenterol Hepatol, 2019,17(7):1253-1264. doi:10.1016/j.cgh.2018.10.028
[46] 王磊, 吴玮, 王刚, 等. 咽喉反流和喉占位性病变病因关系的探讨[J]. 实用医学杂志, 2018,34(21):3617-3620. doi:10.3969/j.issn.1006-5725.2018.21.030 WANG Lei, WU Wei, WANG Gang, et al. Research on the association of laryngeal space occupying lesions and laryngopharyngeal reflux[J]. The Journal of Practical Medicine, 2018, 34(21): 3617-3620. doi:10.3969/j.issn.1006-5725.2018.21.030
[47] Sandner A, Illert J, Koitzsch S, et al. Reflux induces DNA strand breaks and expression changes of MMP1+9+14 in a human miniorgan culture model[J]. Exp Cell Res, 2013,319(19):2905-2915. doi:10.1016/j.yexcr.2013.09.004
[48] Shen S, Jiang J, Yuan Y. Pepsinogen C expression, regulation and its relationship with cancer[J]. Cancer Cell Int, 2017,17:57. doi:10.1186/s12935-017-0426-6
[49] 徐志宇. 胃蛋白酶对喉鳞状细胞癌进展的作用及其初步机制研究[D]. 中国人民解放军海军军医大学, 2022.
[50] Pearson JP, Parikh S, Orlando RC, et al. Review article: reflux and its consequences - the laryngeal, pulmonary and oesophageal manifestations. Conference held in conjunction with the 9th International Symposium on Human Pepsin(ISHP)Kingston-upon-Hull, UK, 21-23 April 2010[J]. Aliment Pharmacol Ther, 2011, 33(1): 1-71. doi:10.1111/j.1365-2036.2011.04581.x
[51] Kim SY, Park B, Lim H, et al. Increased risk of larynx cancer in patients with gastroesophageal reflux disease from a national sample cohort[J]. Clin Otolaryngol, 2019, 44(4): 534-540. doi:10.1111/coa.13328
[52] Venkatesan NN, Pine HS, Underbrink MP. Recurrent respiratory papillomatosis[J]. Otolaryngol Clin North Am, 2012,45(3):671-694
[1] WU Wei, WANG Lei, CHEN Sheng, LI Lianyong, WANG Gang. Multidisciplinary research and advances in gastro-oesophageal reflux disease [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 1-14.
[2] LIU Lianlian, LI Jinrang. Obstructive sleep apnea and laryngopharyngeal reflux [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 15-22.
[3] ZHANG Li, ZHANG Mengru, Alimire Aierken, QIU Zhongmin. Role of pharyngeal reflux in common respiratory diseases [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 23-29.
[4] HU Zhiwei, CHEN Dong, YANG Dong, WU Jimin. Diagnosis and treatment of gastroesophageal airway reflux disease: based on related consensus and guidelines from 2020 to 2024 [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 30-38.
[5] ZHANG Shan, CHEN Qiu, ZHOU Fangwei, MA Yifei. Research progress of biomarkers in laryngopharyngeal reflux disease [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 46-54.
[6] ZHOU Shitong, YANG Yanyan, YANG Yucheng, FANG Hongyan. Pepsin and laryngopharyngeal reflux disease: from pathogenic mechanisms to potential risk factors for pharyngeal and laryngeal squamous cell carcinoma [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 55-60.
[7] XI Xiaoyu, SUI Xinke, CHEN Sheng, LI Lianyong, ZHONG Changqing. Endoscopic treatment of laryngopharyngeal reflux disease [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 61-65.
[8] NIU Yanyan, GU Wei, JIN Xiaofeng, HUO Hong, YANG Dahai, CUI Tingting, WANG Jian. Expression analysis of pepsin in vocal cord leukoplakia tissues [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 66-70.
[9] WANG Lei, WANG Gang, SUN Zhezhe, LIU Hongdan, HAN Haolun, LI Baowei, ZHANG Xiaoli, WU Wei. Correlations between vocal cord hyperplastic lesions, vocal cord leukoplakia, chronic laryngopharyngitis, and laryngopharyngeal reflux [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 71-77.
[10] CUI Xiaohuan, YIN Longlong, ZHANG Yanping, JIANG Xingwang, LI Lina. Study of the association between salivary microbiota and reflux symptoms in patients with laryngopharyngeal reflux [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 78-84.
[11] SUN Zhezhe, WANG Gang, WANG Lei, LI Baowei, HAN Haolun, LIU Hongdan, ZHANG Xiaoli, WU Wei. Influence of body positions on laryngopharyngeal reflux disease [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 91-95.
[12] WEI Xin, XING Dongsheng, ZHAI Zhenwei, YAN Aihui, LIU Zhenyu, CAO Hongwei. Study of the laryngeal reflux symptom index and analysis of influencing factors in pregnant women [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 96-102.
[13] LI Fengjiang, WEI Jie, LIU Hongdan, ZHANG Li, ZHAO Weichao, WU Nana, WANG Lei, WU Wei, WANG Ruijuan. Gastroesophageal reflux disease and laryngopharyngeal reflux disease in 25 elderly patients with pneumonia [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 103-107.
[14] LIU Xiaohong, ZHANG Qingqing, GUO Ruixin, QIANG Yin, SHI Yao, YANG Haonan, CAO Nan, JIA Wei, XIE Meng. Analysis of reflux types in patients with laryngeal reflux associated with Helicobacter pylori infection [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 108-114.
[15] DU Chen, YAN Yan, WANG Li, LU Peiquan. Impact of acid reflux event thresholds on the diagnosis and management of oesophageal reflux disease [J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(6): 115-119.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!