Abstract：The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer is growing year by year. Compared with the other head and neck squamous cell carcinoma, HPV-positive oropharyngeal cancer has unique biological characteristics and better prognosis. According to the 8th edition TNM staging of UICC/AJCC, HPV-positive and HPV-negative oropharyngeal cancer have been classified separately. In 2018, College of American Pathologists and American Society of Clinical Oncology released the guidelines on the HPV testing in head and neck cancer. Several published clinical trials have demonstrated that de-intensified chemoradiation might be efficacious treatment of HPV-positive oropharyngeal cancer.
Mao Guangmin,Xu Tingting,Lu Xueguan. Research progress on diagnosis and treatment of HPV-positive oropharyngeal cancer[J]. Chinese Journal of Radiation Oncology, 2020, 29(11): 1012-1016.
[1] Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States[J]. J Clin Oncol, 2011,29(32):4294-4301. DOI:10.1200/JCO.2011.36.4596. [2] Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial[J]. J Natl Cancer Inst, 2008,100(4):261-269. DOI:10.1093/jnci/djn011. [3] Long W, Yang Z, Li X, et al. HPV-16, HPV-58, and HPV-33 are the most carcinogenic HPV genotypes in Southwestern China and their viral loads are associated with severity of premalignant lesions in the cervix[J]. Virol J, 2018,15(1):94. DOI:10.1186/s12985-018-1003-x. [4] Syrjänen K, Syrjanen S, Pyrhonen S. Human papilloma virus (HPV) antigens in lesions of laryngeal squamous cell carcinomas[J]. ORL J Otorhinolaryngol Relat Spec, 1982, 44(6):323-334. DOI:10.1159/000275612. [5] Castellsague X, Alemany L, Quer M, et al. HPV involvement in head and neck cancers:comprehensive assessment of biomarkers in 3680 patients[J]. J Natl Cancer Inst, 2016, 108(6):djv4036. DOI:10.1093/jnci/djv403. [6] Chakravarthy A, Henderson S, Thirdborough SM, et al. Human papillomavirus drives tumor development throughout the head and neck:improved prognosis is associated with an immune response largely restricted to the oropharynx[J]. J Clin Oncol, 2016,34(34):4132-4141. DOI:10.1200/JCO.2016.68.2955. [7] Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer[J]. N Engl J Med, 2010,363(1):24-35. DOI:10.1056/NEJMoa0912217. [8] Castellsagué X, Mena M, Alemany L. Epidemiology of HPV-positive tumors in europe and in the world[J]. Recen. Results Cancer Res, 2017, 206*1(:27-35. DOI:10.1007/978-3-319-43580-0_2. [9] Chaturvedi AK, Anderson WF, Lortet-Tieulent J, et al. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers[J]. J Clin Oncol, 2013, 31(36):4550-4559. DOI:10.1200/JCO.2013.50.3870. [10] Meng HX, Miao SS, Chen K, et al. Association of p16 as prognostic factors for oropharyngeal cancer:evaluation of p16 in 1470 patients for a 16 year study in Northeast China[J]. Biomed Res Int, 2018, 2018:9594568. DOI:10.1155/2018/9594568. [11] Lam EW, Chan JY, Chan AB, et al. Prevalence, clinicopathological characteristics, and outcome of human papillomavirus-associated oropharyngeal cancer in Southern Chinese patients[J]. Cancer Epidemiol Biomarkers Prev, 2016, 25(1):165-173. DOI:10.1158/1055-9965. EPI-15-0869. [12] Smeets SJ, Hesselink AT, Speel EJ, et al. A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen[J]. Int J Cancer, 2007, 121(11):2465-2472. DOI:10.1002/ijc.22980. [13] Steenbergen RD, Snijders PJ, Heideman DA, et al. Clinical implications of (epi) genetic changes in HPV-induced cervical precancerous lesions[J]. Nat Rev Cancer, 2014,14(6):395-405. DOI:10.1038/nrc3728. [14] Fakhry C, Lacchetti C, Rooper LM, et al. Human papillomavirus testing in head and neck carcinomas:ASCO clinical practice guideline endorsement of the college of American pathologists guideline[J]. J Clin Oncol, 2018, 36(31):3152-3161. DOI:10.1200/JCO.18.00684. [15] Lawrence MS, Sougnez C, Lichtenstein L, et al. Comprehensive genomic characterization of head and neck squamous cell carcinomas[J]. Nature, 2015, 517(7536):576-582. DOI:10.1038/nature14129. [16] Gronhoj C, Jensen DH, Agander T, et al. Deep sequencing of human papillomavirus positive loco-regionally advanced oropharyngeal squamous cell carcinomas reveals novel mutational signature[J]. BMC Cancer, 2018, 18(1):640. DOI:10.1186/s12885-018-4567-3. [17] Keck MK, Zuo Z, Khattri A, et al. Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes[J]. Clin Cancer Res, 2015,21(4):870-881. DOI:10.1158/1078-0432. CCR-14-2481. [18] Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer[J]. N Engl J Med, 2010, 363(1):24-35. DOI:10.1056/NEJMoa0912217. [19] Vawda N, Banerjee RN, Debenham BJ. Impact of smoking on outcomes of HPV-related oropharyngeal cancer treated with primary radiation or surgery[J]. Int J Radiat Oncol Biol Phys, 2019, 103(5):1125-1131. DOI:10.1016/j.ijrobp.2018.11.046. [20] O′Sullivan B, Huang SH, Su J, et al. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S):a multicentre cohort study[J]. Lancet Oncol, 2016, 17(4):440-451. DOI:10.1016/S1470-2045(15)00560-4. [21] National Comprehensive Cancer Network.(NCCN) Clinical Practice Guidelines in Oncology. Head And Neck Cancer, Version 2, 2017.[EB/OL].[2019-03-31].https://www.nccn.org/professionals/physician_gls/default.aspx#head-and-neck. [22] Chera BS, Amdur RJ, Tepper J, et al. Phase 2 trial of de-intensified chemoradiation therapy for favorable-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma[J]. Int J Radiat Oncol Biol Phys, 2015, 93(5):976-985. DOI:10.1016/j.ijrobp.2015.08.033. [23] Chera BS, Amdur RJ, Shen C, et al. Initial results from a phase 2 prospective trial of de-intensified chemoradiation therapy for Low-Risk HPV-associated oropharyngeal squamous cell carcinoma[J]. Int J Radiat Oncol Biol Phys, 2018, 100(5):1309-1310. DOI:10.1016/j.ijrobp.2017.12.026. [24] Marur S, Li S, Cmelak AJ, et al. E1308:Phase Ⅱ Trial of induction chemotherapy followed by reduced-dose radiation and weekly cetuximab in patients with HPV-Associated resectable squamous cell carcinoma of the oropharynx-ECOG-ACRIN Cancer Research Group[J]. J Clin Oncol, 2017, 35(5):490-497. DOI:10.1200/JCO.2016.68.3300. [25] Chen AM, Felix C, Wang PC, et al. Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx:a single-arm, phase 2 study[J]. Lancet Oncol, 2017, 18(6):803-811. DOI:10.1016/S1470-2045(17)30246-2. [26] Seiwert TY, Foster CC, Blair EA, et al. OPTIMA:a phase Ⅱ dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer[J]. Ann Oncol, 2019, 30(2):297-302. DOI:10.1093/annonc/mdy522. [27] Gillison ml, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016):a randomised, multicentre, non-inferiority trial[J]. Lancet, 2019, 393(10166):40-50. DOI:10.1016/S0140-6736(18)32779-X. [28] Mehanna H, Robinson M, Hartley A, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV):an open-label randomised controlled phase 3 trial[J]. Lancet, 2019, 393(10166):51-60. DOI:10.1016/S0140-6736(18)32752-1. [29] Ma DJ, Price K, Moore EJ, et al. Two-year results for MC1273, a phase 2 evaluation of aggressive dose de-escalation for adjuvant chemoradiation in HPV plus oropharynx squamous cell carcinoma (OPSCC)[J]. Int J Radiat Oncol Biol Phys, 2017, 99(5):1320-1320. DOI:10.1016/j.ijrobp.2017.09.021. [30] An Y, Park HS, Kelly JR, et al. The prognostic value of extranodal extension in human papillomavirus-associated oropharyngeal squamous cell carcinoma[J]. Cancer, 2017, 123(14):2762-2772. DOI:10.1002/cncr.30598. [31] Deschuymer S, Mehanna H, Nuyts S. Toxicity reduction in the treatment of HPV positive oropharyngeal cancer:emerging combined modality approaches[J]. Front Oncol, 2018, 8(5):439. DOI:10.3389/fonc.2018.00439. [32] Chow L, Haddad R, Gupta S, et al. Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma:results from the phase Ib KEYNOTE-012 expansion cohort[J]. J Clin Oncol, 2016, 34(32):3838-3845. DOI:10.1200/JCO.2016.68.1478. [33] Ferris RL, Blumenschein G, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck[J]. N Engl J Med, 2016, 375(19):1856-1867. DOI:10.1056/NEJMoa1602252. [34] Schiller JT, Castellsague X, Garland SM. A review of clinical trials of human papillomavirus prophylactic vaccines[J]. Vaccine, 2012, 305(2):F123-F138. DOI:10.1016/j.vaccine.2012.04.108. [35] Gildener-Leapman N, Ferris RL, Bauman JE. Promising systemic immunotherapies in head and neck squamous cell carcinoma[J]. Oral Oncol, 2013, 49(12):1089-1096. DOI:10.1016/j.oraloncology.2013.09.009. [36] Steinau M, Saraiya M, Goodman MT, et al. Human papillomavirus prevalence in oropharyngeal cancer before vaccine introduction, United States[J]. Emerg Infect Dis, 2014, 20(5):822-828. DOI:10.3201/eid2005.131311.
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