Lymph node metastasis in oral squamous cell carcinoma: Where we are and where we are going
Lei-Ming Cao
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Lei-Ming Cao, Nian-Nian Zhong and Zi-Zhan Li contributed equally to this work.
Search for more papers by this authorNian-Nian Zhong
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Lei-Ming Cao, Nian-Nian Zhong and Zi-Zhan Li contributed equally to this work.
Search for more papers by this authorZi-Zhan Li
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Lei-Ming Cao, Nian-Nian Zhong and Zi-Zhan Li contributed equally to this work.
Search for more papers by this authorFang-Yi Huo
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Search for more papers by this authorYao Xiao
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Search for more papers by this authorCorresponding Author
Bing Liu
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Department of Oral and Maxillofacial - Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Correspondence
Bing Liu, State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Email: [email protected]
Lin-Lin Bu, State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Lin-Lin Bu
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Department of Oral and Maxillofacial - Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Correspondence
Bing Liu, State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Email: [email protected]
Lin-Lin Bu, State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Email: [email protected]
Search for more papers by this authorLei-Ming Cao
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Lei-Ming Cao, Nian-Nian Zhong and Zi-Zhan Li contributed equally to this work.
Search for more papers by this authorNian-Nian Zhong
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Lei-Ming Cao, Nian-Nian Zhong and Zi-Zhan Li contributed equally to this work.
Search for more papers by this authorZi-Zhan Li
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Lei-Ming Cao, Nian-Nian Zhong and Zi-Zhan Li contributed equally to this work.
Search for more papers by this authorFang-Yi Huo
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Search for more papers by this authorYao Xiao
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Search for more papers by this authorCorresponding Author
Bing Liu
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Department of Oral and Maxillofacial - Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Correspondence
Bing Liu, State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Email: [email protected]
Lin-Lin Bu, State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Lin-Lin Bu
State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Department of Oral and Maxillofacial - Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China
Correspondence
Bing Liu, State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Email: [email protected]
Lin-Lin Bu, State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Email: [email protected]
Search for more papers by this author[Correction added on 06 December 2023; after first online publication missing sub-sections have been added.]
Abstract
Background
Oral cancer is a common malignant tumour in the head and neck region, with over 90% of cases being oral squamous cell carcinoma (OSCC). Lymph node metastasis (LNM) is a significant adverse prognostic factor in OSCC; however, the mechanism of LNM in OSCC remains unclear, while the strategies for managing cervical lymph nodes (CLNs) in OSCC continue to evolve. At present, neck dissection is necessary for the vast majority of OSCC patients, but complications of surgery can significantly impair patients’ postoperative quality of life. A recent clinical trial discovery indicates that immunotherapy can activate anti-tumour T cells in nearby lymph nodes, leading to vibrant discussions among clinicians about the importance of preserving lymph nodes during surgical treatment.
Aim
This review aims to provide an overview of where we are: the current knowledge of OSCC LNM patterns and management strategies, and where we are going: prospects for clinical and basic research on the issue of OSCC LNM in the era of cancer immunotherapy.
Result
We summarize the general patterns and management strategies of OSCC LNM. The process of LNM in OSCC encompasses four stages: Preparation, Unleash, Migration, and Planting (‘PUMP’ principle). We propose adopting the ‘PRECISE’ model, an overall workflow that includes seven elements—prevention, radiology, preoperative evaluation, chemotherapy, immunotherapy, surgery, and postoperative evaluation—for neck management in OSCC, promoting personalized precision medicine augmented by neoadjuvant therapy. We further discussed recent advances in clinical and basic research on OSCC LNM and provided an outlook on future research directions.
Conclusion
Over the past two centuries, our understanding and management strategies of LNM in OSCC have evolved, seeking more precise and personalized approaches to reduce patient burden and enhance survival and quality of life. Further research should explore lymph nodes’ role in cancer immunotherapy and OSCC interactions, leading to better, less invasive treatments and improved outcomes.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
No data were used for the research described in the article.
REFERENCES
- 1Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71(3): 209-249. doi:10.3322/caac.21660
- 2Speight PM, Farthing PM. The pathology of oral cancer. Br Dent J. 2018; 225(9): 841-847. doi:10.1038/sj.bdj.2018.926
- 3Ferlito A, Silver CE, Rinaldo A. Neck dissection in the new era. J Am Coll Surg. 2007; 204(3): 466-468. doi:10.1016/j.jamcollsurg.2006.11.016
- 4Noguti J, Moura CFGD, Jesus GPPD, et al. Metastasis from oral cancer: an overview. Cancer Genomics Proteomics. 2012; 9(5): 329-335.
- 5Lydiatt WM, Patel SG, O'Sullivan B, et al. Head and neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017; 67(2): 122-137. doi:10.3322/caac.21389
- 6Raffaelli M, Chen AY. Neck dissection: indications, extension, operative technique. In: AL Shifrin, M Raffaelli, GW Randolph, eds. Endocrine Surgery Comprehensive Board Exam Guide. Springer International Publishing; 2021: 247-298.
10.1007/978-3-030-84737-1_11 Google Scholar
- 7Rahim MK, Okholm TLH, Jones KB, et al. Dynamic CD8(+) T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes. Cell. 2023; 186(6): 1127-1143. doi:10.1016/j.cell.2023.02.021.e18
- 8Conway DI, Purkayastha M, Chestnutt IG. The changing epidemiology of oral cancer: definitions, trends, and risk factors. Br Dent J. 2018; 225(9): 867-873. doi:10.1038/sj.bdj.2018.922
- 9Pfister DG, Spencer S, Adkins D, et al. NCCN clinical practice guidelines in oncology (NCCN Guidelines®) head and neck cancers version 1.2023. NCCN. Accessed December 20, 2022. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf
- 10Onuigbo WI. Historical data on the dynamics of lymphatic metastasis. Oncology. 1972; 26(6): 505-514.
- 11Warren JC. Surgical Observations on Tumours: With Cases and Operations. Crocker and Brewster; 1837.
- 12Crile G. Excision of cancer of the head and neck. With special reference to the plan of dissection based on one hundred and thirty-two operations. J Am Med Assoc. 1906; 47(22): 1780-1786. doi:10.1001/jama.1906.25210220006001a
10.1001/jama.1906.25210220006001a Google Scholar
- 13Folz BJ, Silver CE, Rinaldo A, et al. An outline of the history of head and neck oncology. Oral Oncol. 2008; 44(1): 2-9.
- 14Kitagawa T. On a method of X-ray treatment for carcinoma metastasis in cervical lymphnode. Gann. 1958; 49(1): 9-14. doi:10.20772/cancersci1907.49.1_9
- 15Suarez O. El problema de las metastasis linfaticas y alejadas del cancer de laringe e hipofaringe. Rev Otorrinolaringol. 1963; 23: 83-99.
- 16Patel KN, Shah JP. Neck dissection: past, present, future. Surg Oncol Clin N Am. 2005; 14(3): 461-477. doi:10.1016/j.soc.2005.04.003 vi
- 17Galmarini D, Galmarini CM, Galmarini FC. Cancer chemotherapy: a critical analysis of its 60 years of history. Crit Rev Oncol Hematol. 2012; 84(2): 181-199.
- 18Shah JP, Candela FC, Poddar AK. The patterns of cervical lymph node metastases from squamous carcinoma of the oral cavity. Cancer. 1990; 66(1): 109-113. doi:10.1002/1097-0142(19900701)66:1<109::AID-CNCR2820660120>3.0.CO;2-A
10.1002/1097-0142(19900701)66:1<109::AID-CNCR2820660120>3.0.CO;2-A CAS PubMed Web of Science® Google Scholar
- 19Shoaib T, Soutar DS, Prosser JE, et al. A suggested method for sentinel node biopsy in squamous cell carcinoma of the head and neck. Head Neck. 1999; 21(8): 728-733. doi:10.1002/(SICI)1097-0347(199912)21:8<728::AID-HED8>3.0.CO;2-P
10.1002/(SICI)1097-0347(199912)21:8<728::AID-HED8>3.0.CO;2-P CAS PubMed Web of Science® Google Scholar
- 20Padera TP, Meijer EF, Munn LL. The lymphatic system in disease processes and cancer progression. Annu Rev Biomed Eng. 2016; 18: 125-158. doi:10.1146/annurev-bioeng-112315-031200
- 21Dieterich LC, Tacconi C, Ducoli L, Detmar M. Lymphatic vessels in cancer. Physiol Rev. 2022; 102(4): 1837-1879. doi:10.1152/physrev.00039.2021
- 22Gillot L, Baudin L, Rouaud L, Kridelka F, Noel A. The pre-metastatic niche in lymph nodes: formation and characteristics. Cell Mol Life Sci. 2021; 78(16): 5987-6002. doi:10.1007/s00018-021-03873-z
- 23Murai M, Shen X, Huang L, et al. Overexpression of c-met in oral SCC promotes hepatocyte growth factor-induced disruption of cadherin junctions and invasion. Int J Oncol. 2004; 25(4): 831-840.
- 24Lotfi A, Mohammadi G, Tavassoli A, Mousaviagdas M, Chavoshi H, Saniee L. Serum levels of MMP9 and MMP2 in patients with oral squamous cell carcinoma. Asian Pac J Cancer Prev. 2015; 16(4): 1327-1330. doi:10.7314/apjcp.2015.16.4.1327
- 25Zhang Z, Helman JI, Li Lj. Lymphangiogenesis, lymphatic endothelial cells and lymphatic metastasis in head and neck cancer—a review of mechanisms. Int J Oral Sci. 2010; 2(1): 5-14.
- 26Robbins KT, Clayman G, Levine PA, et al. Neck dissection classification update: revisions proposed by the American Head and Neck Society and the American Academy of Otolaryngology–Head and Neck Surgery. Arch Otolaryngol Head Neck Surg. 2002; 128(7): 751-758.
- 27Eisenmenger LB, Wiggins RH. Imaging of head and neck lymph nodes. Radiol Clin. 2015; 53(1): 115-132.
10.1016/j.rcl.2014.09.011 Google Scholar
- 28Iwanaga J, Lofton C, He P, Dumont AS, Tubbs RS. Lymphatic system of the head and neck. J Craniofac Surg. 2021; 32(5): 1901-1905. doi:10.1097/SCS.0000000000007230
- 29Doll C, Mrosk F, Wuester J, et al. Pattern of cervical lymph node metastases in squamous cell carcinoma of the upper oral cavity–how to manage the neck. Oral Oncol. 2022; 130:105898.
- 30Walton E, Cramer JD. Predictors of occult lymph node metastases in lip cancer. Am J Otolaryngol. 2020; 41(3):102419. doi:10.1016/j.amjoto.2020.102419
- 31Kim HW, Kim MY, Kim CH. A systematic review of therapeutic outcomes following treatment of squamous cell carcinoma of the retromolar trigone. J Korean Assoc Oral Maxillofac Surg. 2021; 47(4): 291-314. doi:10.5125/jkaoms.2021.47.4.291
- 32Woolgar JA. The topography of cervical lymph node metastases revisited: the histological findings in 526 sides of neck dissection from 439 previously untreated patients. Int J Oral Maxillofac Surg. 2007; 36(3): 219-225. doi:10.1016/j.ijom.2006.10.014
- 33Morgan-Parkes JH. Metastases: mechanisms, pathways, and cascades. AJR Am J Roentgenol. 1995; 164(5): 1075-1082.
- 34Pantvaidya GH, Pal P, Vaidya AD, Pai PS, D'Cruz AK. Prospective study of 583 neck dissections in oral cancers: implications for clinical practice. Head Neck. 2014; 36(10): 1503-1507. doi:10.1002/hed.23494
- 35d'Alessandro AF, Pinto FR, Lin CS, et al. Oral cavity squamous cell carcinoma: factors related to occult lymph node metastasis. Braz J Otorhinolaryngol. 2015; 81: 248-254.
- 36Roh J, Muelleman T, Tawfik O, Thomas SM. Perineural growth in head and neck squamous cell carcinoma: a review. Oral Oncol. 2015; 51(1): 16-23.
- 37Bittar RF, Ferraro HP, Ribas MH, Lehn CN. Predictive factors of occult neck metastasis in patients with oral squamous cell carcinoma. Braz J Otorhinolaryngol. 2016; 82(5): 543-547.
- 38Melchers L, Schuuring E, Van Dijk B, et al. Tumour infiltration depth⩾ 4 mm is an indication for an elective neck dissection in pT1cN0 oral squamous cell carcinoma. Oral Oncol. 2012; 48(4): 337-342.
- 39Duprez F, Berwouts D, De Neve W, et al. Distant metastases in head and neck cancer. Head Neck. 2017; 39(9): 1733-1743.
- 40Ahuja ATYM. Sonographic evaluation of cervical lymph nodes. AJR Am J Roentgenol. 2005; 184(5): 1691-1699. doi:10.2214/ajr.184.5.01841691
- 41De Cicco C, Trifiro G, Calabrese L, et al. Lymphatic mapping to tailor selective lymphadenectomy in cN0 tongue carcinoma: beyond the sentinel node concept. Eur J Nucl Med Mol Imaging. 2006; 33(8): 900-905. doi:10.1007/s00259-006-0088-4
- 42Chaturvedi P, Datta S, Arya S, et al. Prospective study of ultrasound-guided fine-needle aspiration cytology and sentinel node biopsy in the staging of clinically negative T1 and T2 oral cancer. Head Neck. 2015; 37(10): 1504-1508. doi:10.1002/hed.23787
- 43Liao LJLW, Hsu WL, Wang CT, Lai MS. Detection of cervical lymph node metastasis in head and neck cancer patients with clinically N0 neck-a meta-analysis comparing different imaging modalities. BMC Cancer. 2012; 12: 236. doi:10.1186/1471-2407-12-236
- 44Haberal I, Celik H, Gocmen H, Akmansu H, Yoruk M, Ozeri C. Which is important in the evaluation of metastatic lymph nodes in head and neck cancer: palpation, ultrasonography, or computed tomography? Otolaryngol Head Neck Surg. 2004; 130(2): 197-201. doi:10.1016/j.otohns.2003.08.025
- 45Costantino A, Mercante G, D'Ascoli E, et al. Accuracy of fine-needle aspiration cytology in detecting cervical node metastasis after radiotherapy: systematic review and meta-analysis. Head Neck. 2021; 43(3): 987-996. doi:10.1002/hed.26536
- 46Habib MA, Rahman QB, Hossain S, Imon AA, Kundu GC. Effectiveness of preoperative lymphoscintigraphy for the detection of cervical lymph node metastasis in patients with oral squamous cell carcinoma. Ann Maxillofac Surg. 2017; 7(1): 30-36. doi:10.4103/ams.ams_176_16
- 47Jang SS, Davis ME, Vera DR, Lai SY, Guo TW. Role of sentinel lymph node biopsy for oral squamous cell carcinoma: current evidence and future challenges. Head Neck. 2023; 45(1): 251-265. doi:10.1002/hed.27207
- 48Civantos FJ, Zitsch RP, Schuller DE, et al. Sentinel lymph node biopsy accurately stages the regional lymph nodes for T1-T2 oral squamous cell carcinomas: results of a prospective multi-institutional trial. J Clin Oncol. 2010; 28(8): 1395.
- 49Alkureishi LW, Ross GL, Shoaib T, et al. Sentinel node biopsy in head and neck squamous cell cancer: 5-year follow-up of a European multicenter trial. Ann Surg Oncol. 2010; 17: 2459-2464.
- 50D'Cruz AK, Vaish R, Kapre N, et al. Elective versus therapeutic neck dissection in node-negative oral cancer. N Engl J Med. 2015; 373(6): 521-529. doi:10.1056/NEJMoa1506007
- 51Robbins KT, Shaha AR, Medina JE, et al. Consensus statement on the classification and terminology of neck dissection. Arch Otolaryngol Head Neck Surg. 2008; 134(5): 536-538. doi:10.1001/archotol.134.5.536
- 52Hamoir M, Silver CE, Schmitz S, et al. Radical neck dissection: is it still indicated? Eur Arch Otorhinolaryngol. 2013; 270(1): 1-4. doi:10.1007/s00405-012-2237-7
- 53Pellitteri PK, Robbins KT, Neuman T. Expanded application of selective neck dissection with regard to nodal status. Head Neck. 1997; 19(4): 260-265.
10.1002/(SICI)1097-0347(199707)19:4<260::AID-HED3>3.0.CO;2-Z CAS PubMed Web of Science® Google Scholar
- 54Traynor SJ, Cohen JI, Gray J, Andersen PE, Everts EC. Selective neck dissection and the management of the node-positive neck. Am J Surg. 1996; 172(6): 654-657.
- 55Jin HJ, Park HS. Claudin may be a potential biomarker for epithelial barrier dysfunction in asthma. Allergy Asthma Immunol Res. 2018; 10(1): 4-5. doi:10.4168/aair.2018.10.1.4
- 56Schiff BA, Roberts DB, El-Naggar A, Garden AS, Myers JN. Selective vs modified radical neck dissection and postoperative radiotherapy vs observation in the treatment of squamous cell carcinoma of the oral tongue. Arch Otolaryngol Head Neck Surg. 2005; 131(10): 874-878. doi:10.1001/archotol.131.10.874
- 57Inoue H, Nibu K-i, Saito M, et al. Quality of life after neck dissection. Arch Otolaryngol Head Neck Surg. 2006; 132(6): 662-666. doi:10.1001/archotol.132.6.662
- 58Nibu K-i, Ebihara Y, Ebihara M, et al. Quality of life after neck dissection: a multicenter longitudinal study by the Japanese Clinical Study Group on Standardization of Treatment for Lymph Node Metastasis of Head and Neck Cancer. Int J Clin Oncol. 2010; 15(1): 33-38. doi:10.1007/s10147-009-0020-6
- 59Byers RM, Weber RS, Andrews T, McGill D, Kare R, Wolf P. Frequency and therapeutic implications of “skip metastases” in the neck from squamous carcinoma of the oral tongue. Head Neck. 1997; 19(1): 14-19.
10.1002/(SICI)1097-0347(199701)19:1<14::AID-HED3>3.0.CO;2-Y CAS PubMed Web of Science® Google Scholar
- 60Mishra P, Sharma AK. A 3-year study of supraomohyoid neck dissection and modified radical neck dissection type I in oral cancer: with special reference to involvement of level IV node metastasis. Eur Arch Otorhinolaryngol. 2010; 267(6): 933-938. doi:10.1007/s00405-009-1155-9
- 61Lea J, Bachar G, Sawka AM, et al. Metastases to level IIb in squamous cell carcinoma of the oral cavity: a systematic review and meta-analysis. Head Neck. 2010; 32(2): 184-190. doi:10.1002/hed.21163
- 62Wang H-C, Zheng Y, Pang P, Li R-W, Qi Z-Z, Sun C-F. Discontinuous versus in-continuity neck dissection in squamous cell carcinoma of the tongue and floor of the mouth: comparing the rates of locoregional recurrence. J Oral Maxillofac Surg. 2018; 76(5): 1123-1132.
- 63Dutton JM, Graham SM, Hoffman HT. Metastatic cancer to the floor of mouth: the lingual lymph nodes. Head Neck. 2002; 24(4): 401-405.
- 64McLean T, Kerr SJ, Giddings CEB. Prophylactic dissection of level V in primary mucosal SCC in the clinically N positive neck: a systematic review. Laryngoscope. 2017; 127(9): 2074-2080. doi:10.1002/lary.26573
- 65Hartner L. Chemotherapy for oral cancer. Dent Clin. 2018; 62(1): 87-97.
- 66Shibata H, Saito S, Uppaluri R. Immunotherapy for head and neck cancer: a paradigm shift from induction chemotherapy to neoadjuvant immunotherapy. Review. Front Oncol. 2021; 11:727433. doi:10.3389/fonc.2021.727433
- 67Lee NY, Ferris RL, Psyrri A, et al. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2021; 22(4): 450-462. doi:10.1016/S1470-2045(20)30737-3
- 68Saddawi-Konefka R, Simon AB, Sumner W, Sharabi A, Mell LK, Cohen EEW. Defining the role of immunotherapy in the curative treatment of locoregionally advanced head and neck cancer: promises, challenges, and opportunities. Review. Front Oncol. 2021; 11:738626. doi:10.3389/fonc.2021.738626
- 69Mell L, Torres-Saavedra P, Wong S, et al. Radiotherapy with durvalumab vs. cetuximab in patients with locoregionally advanced head and neck cancer and a contraindication to cisplatin: phase II results of NRG-HN004. Int J Radiat Oncol Biol Phys. 2022; 114(5): 1058.
- 70Marta GN, Riera R, Bossi P, et al. Induction chemotherapy prior to surgery with or without postoperative radiotherapy for oral cavity cancer patients: systematic review and meta-analysis. Eur J Cancer. 2015; 51(17): 2596-2603. doi:10.1016/j.ejca.2015.08.007
- 71Patil VM, Prabhash K, Noronha V, et al. Neoadjuvant chemotherapy followed by surgery in very locally advanced technically unresectable oral cavity cancers. Oral Oncol. 2014; 50(10): 1000-1004. doi:10.1016/j.oraloncology.2014.07.015
- 72Uppaluri R, Campbell KM, Egloff AM, et al. Neoadjuvant and adjuvant pembrolizumab in resectable locally advanced, human papillomavirus–unrelated head and neck cancer: a multicenter, phase II trial. Clin Cancer Res. 2020; 26(19): 5140-5152. doi:10.1158/1078-0432.Ccr-20-1695
- 73Leidner R, Crittenden M, Young K, et al. Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma. J Immunother Cancer. 2021; 9(5):e002485. doi:10.1136/jitc-2021-002485
- 74Ferris RL, Spanos WC, Leidner R, et al. Neoadjuvant nivolumab for patients with resectable HPV-positive and HPV-negative squamous cell carcinomas of the head and neck in the CheckMate 358 trial. J Immunother Cancer. 2021; 9(6):e002568. doi:10.1136/jitc-2021-002568
- 75Darragh LB, Knitz MM, Hu J, et al. A phase I/Ib trial and biological correlate analysis of neoadjuvant SBRT with single-dose durvalumab in HPV-unrelated locally advanced HNSCC. Nature Cancer. 2022; 3(11):13001317. doi:10.1038/s43018-022-00450-6
10.1038/s43018-022-00450-6 Google Scholar
- 76Schoenfeld JD, Hanna GJ, Jo VY, et al. Neoadjuvant nivolumab or nivolumab plus ipilimumab in untreated oral cavity squamous cell carcinoma: a phase 2 open-label randomized clinical trial. JAMA Oncol. 2020; 6(10):15631570. doi:10.1001/jamaoncol.2020.2955
- 77Bois HD, Heim TA, Lund AW. Tumor-draining lymph nodes: at the crossroads of metastasis and immunity. Sci Immunol. 2021; 6(63):eabg3551. doi:10.1126/sciimmunol.abg3551
- 78Lapeyre M, Racadot S, Renard S, et al. Radiotherapy for oral cavity cancers. Cancer/Radiothérapie. 2022; 26(1-2): 189-198.
- 79Hartford AC, Palisca MG, Eichler TJ, et al. American Society for Therapeutic Radiology and Oncology (ASTRO) and American College of Radiology (ACR) practice guidelines for intensity-modulated radiation therapy (IMRT). Int J Radiat Oncol Biol Phys. 2009; 73(1): 9-14.
- 80Henneman R, Rouwenhorst L, Karakullukcu MB, et al. Surgical site complications of isolated salvage neck dissection post-radiotherapy and post-chemoradiotherapy—a cohort analysis (1997-2017). Eur J Surg Oncol. 2023; 49(4): 764-770. doi:10.1016/j.ejso.2022.12.010
- 81Lundin E, Reizenstein J, Landstrom F, Bergqvist M, Lennernas B, Ahlgren J. Radiotherapy as elective treatment of the node-negative neck in oral squamous cell cancer. Anticancer Res. 2021; 41(7): 3489-3498.
- 82Brown J, Shaw R, Bekiroglu F, Rogers SN. Systematic review of the current evidence in the use of postoperative radiotherapy for oral squamous cell carcinoma. Br J Oral Maxillofac Surg. 2012; 50(6): 481-489.
- 83Kämmerer PW, Tribius S, Cohrs L, et al. Adjuvant radiotherapy in patients with squamous cell carcinoma of the oral cavity or oropharynx and solitary ipsilateral lymph node metastasis (pN1)—a prospective multicentric cohort study. Cancers. 2023; 15(6): 1833.
- 84Zecha JAEM, Raber-Durlacher JE, Nair RG, et al. Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols. Support Care Cancer. 2016; 24(6): 2793-2805. doi:10.1007/s00520-016-3153-y
- 85Deshmukh M, Bal M, Deshpande P, Jambhekar NA. Synchronous squamous cell carcinoma of tongue and unicentric cervical Castleman's disease clinically mimicking a stage IV disease: a rare association or coincidence? Head Neck Pathol. 2011; 5(2): 180-183. doi:10.1007/s12105-011-0240-8
- 86Kubo K, Kawahara D, Murakami Y, et al. Development of a radiomics and machine learning model for predicting occult cervical lymph node metastasis in patients with tongue cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2022; 134(1): 93-101. doi:10.1016/j.oooo.2021.12.122
- 87Chen Q, Wei R, Li S. A preoperative nomogram model for the prediction of lymph node metastasis in buccal mucosa cancer. Cancer Med. 2023; 12(13): 14120-14129. doi:10.1002/cam4.6076
- 88Olmeda D, Cerezo-Wallis D, Castellano-Sanz E, Garcia-Silva S, Peinado H, Soengas MS. Physiological models for in vivo imaging and targeting the lymphatic system: nanoparticles and extracellular vesicles. Adv Drug Deliv Rev. 2021; 175:113833. doi:10.1016/j.addr.2021.113833
- 89Mazumder S, Datta S, Ray JG, Chaudhuri K, Chatterjee R. Liquid biopsy: miRNA as a potential biomarker in oral cancer. Cancer Epidemiol. 2019; 58: 137-145. doi:10.1016/j.canep.2018.12.008
- 90Kawaguchi S, Kawahara K, Fujiwara Y, et al. Naringenin potentiates anti-tumor immunity against oral cancer by inducing lymph node CD169-positive macrophage activation and cytotoxic T cell infiltration. Cancer Immunol Immunother. 2022; 71(9): 2127-2139. doi:10.1007/s00262-022-03149-w
- 91Ho AS, Kim S, Tighiouart M, et al. Metastatic lymph node burden and survival in oral cavity cancer. J Clin Oncol. 2017; 35(31): 3601-3609. doi:10.1200/jco.2016.71.1176
- 92Kim JH, Ku M, Yang J, Byeon HK. Recent developments of ICG-guided sentinel lymph node mapping in oral cancer. Diagnostics (Basel). 2021; 11(5): 891. doi:10.3390/diagnostics11050891
- 93Mockelmann N, Lorincz BB, Knecht R. Robotic-assisted selective and modified radical neck dissection in head and neck cancer patients. Int J Surg. 2016; 25: 24-30. doi:10.1016/j.ijsu.2015.11.022
- 94Jimenez-Maggiora GA, Bruschi S, Qiu H, So JS, Aisen PS. ATRI EDC: a novel cloud-native remote data capture system for large multicenter Alzheimer's disease and Alzheimer's disease-related dementias clinical trails. JAMIA Open. 2022; 5(1):ooab119. doi:10.1093/jamiaopen/ooab119
- 95Darragh LB, Gadwa J, Pham TT, et al. Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors. Nat Commun. 2022; 13(1): 7015. doi:10.1038/s41467-022-34676-w
- 96Saddawi-Konefka R, O'Farrell A, Faraji F, et al. Lymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC. Nat Commun. 2022; 13(1): 4298. doi:10.1038/s41467-022-31941-w
- 97Mermod M, Hiou-Feige A, Bovay E, et al. Mouse model of postsurgical primary tumor recurrence and regional lymph node metastasis progression in HPV-related head and neck cancer. Int J Cancer. 2018; 142(12): 2518-2528. doi:10.1002/ijc.31240
- 98Bower NI, Vogrin AJ, Le Guen L, et al. Vegfd modulates both angiogenesis and lymphangiogenesis during zebrafish embryonic development. Development. 2017; 144(3): 507-518. doi:10.1242/dev.146969
- 99Ha SW, Lee HJ, Cho AS, Hwang SI, Lee HJ. Evaluation of lymph node metastasis in a rabbit tumor model: correlations between contrast-enhanced ultrasound and pathologic findings. Ultrasonography. 2020; 39(1): 60-69. doi:10.14366/usg.19010
- 100Habanjar O, Diab-Assaf M, Caldefie-Chezet F, Delort L. 3D cell culture systems: tumor application, advantages, and disadvantages. Int J Mol Sci. 2021; 22(22):12200. doi:10.3390/ijms222212200
- 101Low LA, Mummery C, Berridge BR, Austin CP, Tagle DA. Organs-on-chips: into the next decade. Nat Rev Drug Discovery. 2021; 20(5): 345-361. doi:10.1038/s41573-020-0079-3
- 102Gil JF, Moura CS, Silverio V, Gonçalves G, Santos HA. Cancer models on chip: paving the way to large scale trial applications. Adv Mater. 2023;e2300692. doi:10.1002/adma.202300692
- 103Shanti A, Hallfors N, Petroianu GA, Planelles L, Stefanini C. Lymph nodes-on-chip: promising immune platforms for pharmacological and toxicological applications. Front Pharmacol. 2021; 12:711307. doi:10.3389/fphar.2021.711307
- 104Liu J, Li H-J, Luo Y-L, et al. Enhanced primary tumor penetration facilitates nanoparticle draining into lymph nodes after systemic injection for tumor metastasis inhibition. ACS Nano. 2019; 13(8): 8648-8658. doi:10.1021/acsnano.9b03472
- 105Yan H, Li Y, Cheng S, Zeng Y. Advances in analytical technologies for extracellular vesicles. Anal Chem. 2021; 93(11): 4739-4774. doi:10.1021/acs.analchem.1c00693
- 106Wang S-H, Liou G-G, Liu S-H, et al. Laminin γ2-enriched extracellular vesicles of oral squamous cell carcinoma cells enhance in vitro lymphangiogenesis via integrin α3-dependent uptake by lymphatic endothelial cells. Int J Cancer. 2019; 144(11): 2795-2810. doi:10.1002/ijc.32027
- 107Wang J, Man Q-W, Fu Q-Y, et al. Preliminary extracellular vesicle profiling in drainage fluid after neck dissection in OSCC. J Dent Res. 2023; 102(2): 178-186. doi:10.1177/00220345221130013
- 108Wang S, Zhang MJ, Wu ZZ, et al. GSDME is related to prognosis and response to chemotherapy in oral cancer. J Dent Res. 2022; 101(7): 848-858. doi:10.1177/00220345211073072
- 109Wang Z, Zhang H, Zhai Y, Li F, Shi X, Ying M. Single-cell profiling reveals heterogeneity of primary and lymph node metastatic tumors and immune cell populations and discovers important prognostic significance of CCDC43 in oral squamous cell carcinoma. Front Immunol. 2022; 13:843322. doi:10.3389/fimmu.2022.843322
- 110Pour M, Yanai I. New adventures in spatial transcriptomics. Dev Cell. 2022; 57(10): 1209-1210. doi:10.1016/j.devcel.2022.04.021
- 111Wu D, Liu X, Zhang J, Li L, Wang X. Significance of single-cell and spatial transcriptomes in cell biology and toxicology. Cell Biol Toxicol. 2021; 37(1): 1-5. doi:10.1007/s10565-020-09576-8
- 112Wang DC, Wang X. Discovery in clinical and translational medicine. Clin Transl Med. 2021; 11(10):e568. doi:10.1002/ctm2.568
