Journal of Prevention and Treatment for Stomatological Diseases ›› 2021, Vol. 29 ›› Issue (1): 65-68.doi: 10.12016/j.issn.2096-1456.2021.01.011

• Review Articles • Previous Articles     Next Articles

Research progress on HPV-positive oropharyngeal carcinoma sensitive to radiation therapy

CHEN Yongju(),HUANG Zixian,CHEN Rui,CHEN Weiliang()   

  1. Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
  • Received:2020-03-07 Revised:2020-08-25 Online:2021-01-20 Published:2020-11-18
  • Contact: Weiliang CHEN;
  • Supported by:
    general program of National Natural Science Foundation of China(81772888)


Oropharyngeal carcinoma is a highly heterogeneous disease that is mainly caused by tobacco and alcohol abuse or high-risk human papillomavirus (HPV) infection. HPV-positive oropharyngeal carcinoma and HPV-negative oropharyngeal carcinoma have obvious differences in etiology, epidemiology and prognosis; therefore, different methods should be adopted for treatment. It is known that the TP53 gene is not mutated in HPV-positive oropharyngeal carcinoma, and radiation therapy can activate it and induce cell apoptosis via DNA damage. There are common repair pathways to DNA damage, such as nonhomologous end joining, and this pathway is more sensitive to radiotherapy under the inhibition of HPV oncoprotein. In addition, the further activation of the immune response under the effect of radiation also participates in the elimination of tumors. In this paper, we reviewed the research on the sensitivity of HPV-positive oropharyngeal cancer to radiotherapy to provide a scientific basis for targeted treatment for various pathogenic factors and clinical stages of oropharyngeal cancer in the future.

Key words: oropharyngeal carcinoma, human papillomavirus, radiosensitization, DNA damage, tumor protein p53, non-homologous end joining, immune response, apoptosis

CLC Number: 

  • R78
[1] Mirabello L, Clarke MA, Nelson CW , et al. The intersection of HPV epidemiology, genomics and mechanistic studies of HPV-mediated carcinogenesis[J]. Viruses, 2018,10(2):80. doi: 10.3390/v10020080.
doi: 10.3390/v10020080
[2] Hoppe-Seyler K, Bossler F, Braun JA , et al. The HPV E6/E7 Oncogenes: key factors for viral carcinogenesis and therapeutic targets[J]. Trends Microbiol, 2018,26(2):158-168. doi: 10.1016/j.tim.2017.07.007.
doi: 10.1016/j.tim.2017.07.007 pmid: 28823569
[3] Scheffner M, Werness BA Huibregtse JM , et al. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53[J]. Cell, 1990,63(6):1129-1136. doi: 10.1016/0092-8674(90)90409-8.
doi: 10.1016/0092-8674(90)90409-8 pmid: 2175676
[4] Taberna M, Mena M, Pavón MA , et al. Human papillomavirus-related oropharyngeal cancer[J]. Ann Oncol, 2017,28(10):2386-2398. doi: 10.1093/annonc/mdx304.
doi: 10.1093/annonc/mdx304 pmid: 28633362
[5] Götz C, Bischof C, Wolff KD , et al. Detection of HPV infection in head and neck cancers: promise and pitfalls in the last ten years: a meta-analysis[J]. Mol Clin Oncol, 2019,10(1):17-28. doi: 10.3892/mco.2018.1749.
doi: 10.3892/mco.2018.1749 pmid: 30655973
[6] Senkomago V, Henley SJ, Thomas CC , et al. Human papillomavirus-attributable cancers-united states, 2012-2016[J]. MMWR Morb Mortal Wkly Rep, 2019,68(33):724-728. doi: 10.15585/mmwr.mm6833a3.
doi: 10.15585/mmwr.mm6833a3 pmid: 31437140
[7] Amin MB, Greene FL, Edge SB , et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging[J]. CA Cancer J Clin, 2017,67(2):93-99. doi: 10.3322/caac.21388.
doi: 10.3322/caac.21388 pmid: 28094848
[8] Prevc A, Kranjc S, Cemazar M , et al. Dose-modifying factor of radiation therapy with concurrent cisplatin treatment in HPV-positive squamous cell carcinoma: a preclinical study[J]. Radiat Res, 2018,189(6):644-651. doi: 10.1667/RR14984.1.
doi: 10.1667/RR14984.1 pmid: 29652621
[9] Singh RD, Patel KR, Patel PS . "p53 mutation spectrum and its role in prognosis of oral cancer patients: a study from Gujarat, West India"[J]. Mut Res, 2016,783:15-26. doi: 10.1016/j.mrfmmm.2015.12.001.
[10] Zhou G, Liu Z, Myers JN . TP53 mutations in head and neck squamous cell carcinoma and their impact on disease progression and treatment response[J]. J Cell Biochem, 2016,117(12):2682-2692. doi: 10.1002/jcb.25592.
doi: 10.1002/jcb.25592 pmid: 27166782
[11] Liu C, Mann D, Sinha UK , et al. The molecular mechanisms of increased radiosensitivity of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC): an extensive review[J]. J Otolaryngol Head Neck Surg, 2018,47(1):59. doi: 10.1186/s40463-018-0302-y.
doi: 10.1186/s40463-018-0302-y pmid: 30241572
[12] Wang H, Wang B, Wei J , et al. Molecular mechanisms underlying increased radiosensitivity in human papillomavirus-associated oropharyngeal squamous cell carcinoma[J]. Int J Biol Sci, 2020,16(6):1035-1043. doi: 10.7150/ijbs.40880.
doi: 10.7150/ijbs.40880 pmid: 32140071
[13] Steve, Seltzsam, Frank , et al. In HPV-positive HNSCC cells, functional restoration of the p53/p21 pathway by proteasome inhibitor bortezomib does not affect radio- or chemosensitivity[J]. Transl Oncol, 2019,12(3):417-25. doi: 10.1016/j.tranon.2018.11.013.
doi: 10.1016/j.tranon.2018.11.013 pmid: 30554133
[14] Barnes RP, Fouquerel E, Opresko PL . The impact of oxidative DNA damage and stress on telomere homeostasis[J]. Mech Ageing Dev, 2018,177:37-45. doi: 10.1016/j.mad.2018.03.013.
doi: 10.1016/j.mad.2018.03.013 pmid: 29604323
[15] Vitti ET, Parsons JL . The radiobiological effects of proton beam therapy: impact on DNA damage and repair[J]. Cancers(Basel), 2019,11(7):946. doi: 10.3390/cancers11070946.
[16] Piazza A, Heyer WD . Homologous recombination and the formation of complex genomic rearrangements[J]. Trends Cell Biol, 2019,29(2):135-149. doi: 10.1016/j.tcb.2018.10.006.
doi: 10.1016/j.tcb.2018.10.006 pmid: 30497856
[17] Chang HHY, Pannunzio NR, Adachi N , et al. Non-homologous DNA end joining and alternative pathways to double-strand break repair[J]. Nat Rev Mol Cell Biol, 2017,18(8):495-506. doi: 10.1038/nrm.2017.48.
doi: 10.1038/nrm.2017.48 pmid: 28512351
[18] Wieringa HW, van der Zee AG, de Vries EG , et al. Breaking the DNA damage response to improve cervical cancer treatment[J]. Cancer Treat Rev, 2016,42:30-40. doi: 10.1016/j.ctrv.2015. 11.008.
doi: 10.1016/j.ctrv.2015.11.008 pmid: 26643553
[19] Lyu X, Zhang M, Li G , et al. PD-1 and PD-L1 expression predicts radiosensitivity and clinical outcomes in head and neck cancer and is associated with HPV infection[J]. J Cancer, 2019,10(4):937-948. doi: 10.7150/jca.27199.
doi: 10.7150/jca.27199 pmid: 30854100
[20] Rödel F, Martin D, Balermpas P , et al. Modulation of radiation sensitivity and antitumor immunity by viral pathogenic factors: implications for radio-immunotherapy[J]. Biochim Biophys Acta Rev Cancer, 2019,1871(1):126-137. doi: 10.1016/j.bbcan.2018. 12.006.
doi: 10.1016/j.bbcan.2018.12.006 pmid: 30605716
[21] Kim HS, Lee JY, Lim SH , et al. Association between PD-L1 and HPV status and the prognostic value of PD-L1 in oropharyngeal squamous cell carcinoma[J]. Cancer Res Treat, 2016; 48(2):527-536. doi: 10.4143/crt.2015.249.
doi: 10.4143/crt.2015.249 pmid: 26511814
[22] Seiwert TY, Burtness B, Mehra R , et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial[J]. Lancet Oncol, 2016,17(7):956-965. doi: 10.1016/S1470-2045(16)30066-3.
doi: 10.1016/S1470-2045(16)30066-3 pmid: 27247226
[1] SONG Bingqing,REN Biao,CHENG Lei. Research progress on the relationship between Fusobacterium nucleatum and periodontitis [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2021, 29(8): 557-561.
[2] SHI Yangyang,ZHOU Xuedong,CHENG Lei,REN Biao. The relationship between Candida albicans infection and oral cancer [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2021, 29(2): 119-123.
[3] ZHENG Xu,XIE Chen,GAO Chang,GUO Zhuling. Research progress on the relationship between IL-37 and periodontitis [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2021, 29(12): 859-864.
[4] WANG Wanrong,GU Junting,GAO Peng,LI Jing,WAN Meichen,JIAO Kai,NIU Lina. Progress in the application of metal and metal oxide nanoparticles in the antibacterial modification of dental materials [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2020, 28(8): 540-544.
[5] XU Bin,BI Liangjia. Research progress of sonodynamic therapy in the field of stomatology [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2020, 28(8): 535-539.
[6] WU Fayin,XU Haili. Effect and mechanism of allicin combined with 5-fluorouracil on proliferation and apoptosis of the MEC-1 cell line in mucoepidermoid carcinoma [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2020, 28(6): 355-360.
[7] ZHANG Zheng,WANG Zuomin. Role of B cell activating factor in the development of periodontitis [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2020, 28(12): 796-800.
[8] ZHU Xuanzhi,MA Rui,XIE Xudong,WANG Jun. Research progress on the relationship between osteocytes and periodontitis [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2020, 28(12): 801-805.
[9] ZHOU Jiaqi,SHU Linjing,XIONG Yi,ZHANG Yixin,XIANG Lin,WU Yingying. Study on the role of FoxO1 in the regulation of osteoblastic metabolism by 1,25(OH)2D3 in a high glucose environment [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2020, 28(1): 24-29.
[10] Xinyuan LEI,Xinyu LIN,Zhanpeng OU,Yi RUAN,Jinsong LI. Mitochondrial fission protein 1 determines mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(6): 350-354.
[11] LIN Lin,DUAN Ning,WANG Xiang,JIANG Hongliu,WANG Wenmei. Oral verrucous xanthoma in adolescents: a case report and literature review [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(5): 318-320.
[12] HUANG Lihuan,JIANG Yingtong,OUYANG Kexiong,WU Lihong,YANG Xuechao. Research progress on the role and mechanism of miR-155 in the development of oral squamous cell carcinoma [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(12): 809-812.
[13] WANG Min, GE Song. Research progress on the T cell receptor CDR3 spectral sequence of periodontitis [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(12): 799-803.
[14] ZENG Sujuan,PENG Bo,CHENG Weidong,WEI Dongfeng,HUANG Wenyan,LI Yunyang,ZHAO Wanghong. Experimental study on the effect of hedysarum polybotys saccharides and selenizated hedysarum polybotys saccharides on oral squamous cancer cells in vitro [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(12): 757-762.
[15] GUO Xinwei,ZHAO Hongyan,YANG Yaoyao,QIAN Xin,LING Xiaoxu,ZHANG Zhimin. Research progress of periodontitis and periodontal dysbiosis [J]. Journal of Prevention and Treatment for Stomatological Diseases, 2019, 27(11): 739-744.
Full text



[1] ZHU Song-song, HU Jing. The application of distraction osteogenesis in the temporomandibular joint ankylosis and secondary dentofacial deformities[J]. journal1, 2016, 24(1): 6 -10 .
[2] XU Jing. The influence of the impacted mandibular third molar extraction on the distal periodontal tissue of the mandibular second molar[J]. journal1, 2016, 24(1): 11 -14 .
[3] ZHONG Jiang-long, PAN Ji-yang, CHEN Wei-liang. The evaluation of Eagle syndrome treatment by surgery combined with antidepressant therapy[J]. journal1, 2016, 24(1): 26 -28 .
[4] CHEN Xi, SUN Qin-zhou. The study of colorimetric board of porcelain fused to metal restoration for moderate to severe dental fluorosis[J]. journal1, 2016, 24(1): 33 -36 .
[5] OUYANG Ke-xiong1, LIANG Jun, ZOU Rui, LI Zhi-qiang, BAI Zhi-bao, PIAO Zheng-guo, ZHAO Jian-Jiang.. Ion Torrent RNA-Seq detection and analysis of the long non-coding RNA in tongue squamous cell carcinoma[J]. journal1, 2016, 24(1): 15 -19 .
[6] YU Pei, XUE Jing, ZHANG Xiao-wei, ZHENG Cang-shang. The influence of the roughness of zirconia ceramic surface on microbial attachment[J]. journal1, 2016, 24(1): 20 -25 .
[7] LIU Fang. Clinical assessment of two fissure sealant techniques in children’s dental caries prevention[J]. journal1, 2016, 24(1): 44 -45 .
[8] . [J]. journal1, 2016, 24(1): 49 -52 .
[9] LU Jian-rong, BAN Hua-jie, WANG Dai-you, ZHOU Hui-hui, LONG Ru, QIN Shu-hua. Clinical observation of sternocleidomastoid muscle flaps combined with artificial biological membrane reparing the defects after parotidectomy[J]. journal1, 2016, 24(1): 29 -32 .
[10] LI Bin, HE Xiao-ning, GAO Yuan, HU Yu-ping. Clinical analysis of pain after two kinds of apical stop preparation[J]. journal1, 2016, 24(1): 40 -43 .
This work is licensed under a Creative Commons Attribution 3.0 License.