{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T20:58:15Z","timestamp":1785790695643,"version":"3.56.0"},"reference-count":63,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,8]],"date-time":"2023-10-08T00:00:00Z","timestamp":1696723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The American Joint Committee on Cancer (AJCC), in its 8th edition, introduces modifications to the previous TNM classification, incorporating tumour depth of invasion (DOI). The aim of this research is to analyse the prognosis (in terms of disease-free survival and overall survival) of clinical early stage (I and II) squamous cell carcinomas of the oral tongue according to the DOI levels established by the AJCC in its latest TNM classification to assess changes to the T category and global staging system and to evaluate the association between DOI and other histological risk factors. Methods: A retrospective longitudinal observational study of a series of cases was designed. All patients were treated with upfront surgery at our institution between 2010 and 2019. The variables of interest were defined and classified into four groups: demographic, clinical, histological and evolutive control. Univariate and multivariate analyses were carried out and survival functions were calculated using the Kaplan\u2013Meier method. Statistical significance was established for p values below 0.05. Results: Sixty-one patients were included. The average follow-up time was 47.42 months. Fifteen patients presented a loco-regional relapse (24.59%) and five developed distant disease (8.19%). Twelve patients died (19.67%). Statistically significant differences were observed, with respect to disease-free survival (p = 0.043), but not with respect to overall survival (p = 0.139). A total of 49.1% of the sample upstaged their T category and 29.5% underwent modifications of their global stage. The analysis of the relationship between DOI with other histological variables showed a significant association with the presence of pathological cervical nodes (p = 0.012), perineural invasion (p = 0.004) and tumour differentiation grade (p = 0.034). Multivariate analysis showed association between depth of invasion and perineural invasion. Conclusions: Depth of invasion is a histological risk factor in early clinical stages of oral tongue squamous cell carcinoma. Depth of invasion impacts negatively on patient prognosis, is capable per se of modifying the T category and the global tumour staging, and is associated with the presence of cervical metastatic disease, perineural invasion and tumoural differentiation grade.<\/jats:p>","DOI":"10.3390\/cancers15194882","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T04:56:43Z","timestamp":1696827403000},"page":"4882","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Depth of Invasion: Influence of the Latest TNM Classification on the Prognosis of Clinical Early Stages of Oral Tongue Squamous Cell Carcinoma and Its Association with Other Histological Risk Factors"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1890-9725","authenticated-orcid":false,"given":"Ignacio","family":"Navarro Cu\u00e9llar","sequence":"first","affiliation":[{"name":"Oral and Maxillofacial Surgery Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Esp\u00edas Alonso","sequence":"additional","affiliation":[{"name":"Private Practice, Sta. Susana, 41, 33007 Oviedo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Alijo Serrano","sequence":"additional","affiliation":[{"name":"Pathology Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Herrera Herrera","sequence":"additional","affiliation":[{"name":"Radiology Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Javier","family":"Zamorano Le\u00f3n","sequence":"additional","affiliation":[{"name":"Public Health and Maternal & Child Health Department, School of Medicine, Universidad Complutense, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3500-2917","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Del Castillo Pardo de Vera","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Department, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Mar\u00eda","family":"L\u00f3pez L\u00f3pez","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2606-8997","authenticated-orcid":false,"given":"Cristina","family":"Maza Muela","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gema","family":"Arenas de Frutos","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3576-6498","authenticated-orcid":false,"given":"Santiago","family":"Ochandiano Caicoya","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3329-4896","authenticated-orcid":false,"given":"Manuel","family":"Tousidonis Rial","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9466-926X","authenticated-orcid":false,"given":"Alba","family":"Garc\u00eda Sevilla","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"Ant\u00fanez-Conde","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Department, Hospital Universitario Ruber Juan Bravo, 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Cebri\u00e1n Carretero","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Department, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Isabel","family":"Garc\u00eda-Hidalgo Alonso","sequence":"additional","affiliation":[{"name":"Radiology Department, Hospital Universitario Puerta de Hierro, 28222 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Ignacio","family":"Salmer\u00f3n Escobar","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Burgue\u00f1o Garc\u00eda","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Department, Hospital Universitario La Paz, 28046 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Navarro Vila","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9869-9240","authenticated-orcid":false,"given":"Carlos","family":"Navarro Cu\u00e9llar","sequence":"additional","affiliation":[{"name":"Oral and Maxillofacial Surgery Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","first-page":"11884","article-title":"Essentials of oral cancer","volume":"8","author":"Rivera","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"104627","DOI":"10.1016\/j.oraloncology.2020.104627","article-title":"Management of early oral cavity squamous cancers","volume":"104","author":"Chatterjee","year":"2020","journal-title":"Oral Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.oraloncology.2012.08.006","article-title":"Outcome of patients with early stage oral cancer managed by an observation strategy towards the N0 neck using ultrasound guided fine needle aspiration cytology: No survival difference as compared to elective neck dissection","volume":"49","author":"Flach","year":"2013","journal-title":"Oral Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1056\/NEJMoa1506007","article-title":"Elective versus Therapeutic Neck Dissection in Node-Negative Oral Cancer","volume":"373","author":"Vaish","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/s41416-019-0587-2","article-title":"Nationwide randomised trial evaluating elective neck dissection for early stage oral cancer (SEND study) with meta-analysis and concurrent real-world cohort","volume":"121","author":"Hutchison","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1016\/j.ejca.2015.08.023","article-title":"Sentinel European Node Trial (SENT): 3-year results of sentinel node biopsy in oral cancer","volume":"51","author":"Schilling","year":"2015","journal-title":"Eur. J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1159\/000276274","article-title":"Elective radiotherapy of the neck in patients with squamous cell carcinoma of the head and neck","volume":"54","author":"Boysen","year":"1992","journal-title":"ORL J. Otorhinolaryngol. Relat. Spec."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.oraloncology.2011.11.007","article-title":"Tumour infiltration depth \u2265 4 mm is an indication for an elective neck dissection in pT1cN0 oral squamous cell carcinoma","volume":"48","author":"Melchers","year":"2012","journal-title":"Oral Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1002\/cncr.24161","article-title":"Predictive value of tumor thickness for cervical lymph-node involvement in squamous cell carcinoma of the oral cavity: A meta-analysis of reported studies","volume":"115","author":"Huang","year":"2009","journal-title":"Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Faisal, M., Abu Bakar, M., Sarwar, A., Adeel, M., Batool, F., Malik, K.I., Jamshed, A., and Hussain, R. (2018). Depth of invasion (DOI) as a predictor of cervical nodal metastasis and local recurrence in early stage squamous cell carcinoma of oral tongue (ESSCOT). PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0202632"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.joms.2015.09.015","article-title":"Tumor Infiltration Depth as Predictor of Nodal Metastasis in Early Tongue Squamous Cell Carcinoma","volume":"74","author":"Tarsitano","year":"2016","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1002\/hed.20275","article-title":"Importance of tumor thickness and depth of invasion in nodal involvement and prognosis of oral squamous cell carcinoma: A review of the literature","volume":"27","author":"Pentenero","year":"2005","journal-title":"Head Neck"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/S0030-6665(05)70076-1","article-title":"Nodal metastases: Predictive factors","volume":"31","author":"Kowalski","year":"1998","journal-title":"Otolaryngol. Clin. North Am."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/hed.2880110502","article-title":"Evaluation of some prognostic factors in small squamous cell carcinoma of the mobile tongue: A multicenter study in Sweden","volume":"11","author":"Nathanson","year":"1989","journal-title":"Head Neck"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.ijom.2016.11.003","article-title":"Squamous cell carcinoma of the anterior tongue: Is tumour thickness an indicator for cervical metastasis?","volume":"46","author":"Loganathan","year":"2017","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S1368-8375(02)00142-2","article-title":"Tumour thickness predicts cervical nodal metastases and survival in early oral tongue cancer","volume":"39","author":"charoenrat","year":"2003","journal-title":"Oral Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"122","DOI":"10.3322\/caac.21389","article-title":"Head and Neck cancers-major changes in the American Joint Committee on cancer eighth edition cancer staging manual","volume":"67","author":"Lydiatt","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_20","first-page":"55","article-title":"Staging Head and Neck Cancers","volume":"Volume 1","author":"Amit","year":"2017","journal-title":"AJCC Cancer Staging Manual"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S76","DOI":"10.1097\/SAP.0000000000002346","article-title":"Functional Outcomes Regarding Facial Artery Musculomucosal Flap for Reconstruction of Partial Glossectomy Defects","volume":"85","author":"Benjamin","year":"2020","journal-title":"Ann. Plast. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1097\/PRS.0b013e3181f44742","article-title":"A strategic approach for tongue reconstruction to achieve predictable and improved functional and aesthetic outcomes","volume":"126","author":"Engel","year":"2010","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.coms.2014.05.003","article-title":"Maxillofacial reconstruction with nasolabial and facial artery musculomucosal flaps","volume":"26","author":"Braasch","year":"2014","journal-title":"Oral Maxillofac. Surg. Clin. North Am."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Navarro Vila, C. (2015). Reconstructive Oral and Maxillofacial Surgery, Springer.","DOI":"10.1007\/978-3-319-20487-1"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1002\/hed.24679","article-title":"Treatment-related determinants of survival in early-stage (T1-2N0M0) oral cavity cancer: A population-based study","volume":"39","author":"Sowder","year":"2017","journal-title":"Head Neck"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.ijom.2006.01.006","article-title":"Treatment results and prognostic factors in oral tongue cancer: Analysis of 80 patients","volume":"35","author":"Aksu","year":"2006","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1002\/hed.21033","article-title":"Prospective randomized study of selective neck dissection versus observation for N0 neck of early tongue carcinoma","volume":"31","author":"Yuen","year":"2009","journal-title":"Head Neck"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1002\/hed.25739","article-title":"Surgical consensus guidelines on sentinel node biopsy (SNB) in patients with oral cancer","volume":"41","author":"Schilling","year":"2019","journal-title":"Head Neck"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3843","DOI":"10.1007\/s00405-017-4740-3","article-title":"Diagnostic value of sentinel lymph node biopsy for cT1\/T2N0 tongue squamous cell carcinoma: A meta-analysis","volume":"274","author":"Yang","year":"2017","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1001\/archsurg.1986.01400120060009","article-title":"Thickness as prognostic aid in upper aerodigestive tract cancer","volume":"121","author":"Moore","year":"1986","journal-title":"Arch. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/hed.2880170604","article-title":"Micrometastases in carcinoma of the upper aerodigestive tract: Detection, risk of metastasizing, and prognostic value of depth of invasion","volume":"17","author":"Ambrosch","year":"1995","journal-title":"Head Neck"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1093\/ajcp\/94.5.624","article-title":"Microstaging of squamous cell carcinomas","volume":"94","author":"Breuninger","year":"1990","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/jso.2930310209","article-title":"Cervical lymph node metastases of oral carcinoma related to the depth of invasion of the primary lesion","volume":"31","author":"Thompson","year":"1986","journal-title":"J. Surg. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1097\/00000658-197011000-00017","article-title":"Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma","volume":"172","author":"Breslow","year":"1970","journal-title":"Ann. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1054\/bjom.1999.0034","article-title":"T2 carcinoma of the tongue: The histopathologist\u2019s perspective","volume":"37","author":"Woolgar","year":"1999","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1288\/00005537-199505000-00008","article-title":"Relationship of biopsy and final specimens in evaluation of tumor thickness in floor of mouth carcinoma","volume":"105","author":"Karas","year":"1995","journal-title":"Laryngoscope"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1001\/archotol.1994.01880310023005","article-title":"Tumor thickness in early tongue cancer","volume":"120","author":"Morton","year":"1994","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1001\/archotol.1992.01880050029006","article-title":"Prognostic factors in the recurrence of stage I and II squamous cell cancer of the oral cavity","volume":"118","author":"Jones","year":"1992","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/j.0904-2512.2004.00178.x","article-title":"The relationship of proliferating cell density at the invasive tumour front with prognostic and risk factors in human oral squamous cell carcinoma","volume":"33","author":"Tumuluri","year":"2004","journal-title":"J. Oral Pathol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1097\/00005537-199905000-00021","article-title":"Predictive factors of nodal metastases in oral cavity and oropharynx carcinomas","volume":"109","author":"Giacomarra","year":"1999","journal-title":"Laryngoscope"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/S1368-8375(01)00081-1","article-title":"Importance of tumour thickness measurement in prognosis of tongue cancer","volume":"38","author":"Esteban","year":"2002","journal-title":"Oral Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1001\/jamaoto.2014.1548","article-title":"Primary tumor staging for oral cancer and a proposed modification incorporating depth of invasion: An international multicenter retrospective study","volume":"140","author":"Ebrahimi","year":"2014","journal-title":"JAMA Otolaryngol\u2014Head Neck Surg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.oraloncology.2018.04.018","article-title":"AJCC 8th Edition oral cavity squamous cell carcinoma staging\u2014Is it an improvement on the AJCC 7th Edition?","volume":"82","author":"Pollaers","year":"2018","journal-title":"Oral Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.bjoms.2017.11.009","article-title":"Prognosis of oral cancer: A comparison of the staging systems given in the 7th and 8th editions of the American Joint Committee on Cancer Staging Manual","volume":"56","author":"Tirelli","year":"2018","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.oraloncology.2017.05.020","article-title":"External validation of the AJCC Cancer Staging Manual, 8th edition, in an independent cohort of oral cancer patients","volume":"71","author":"Matos","year":"2017","journal-title":"Oral Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1002\/hed.25553","article-title":"Prognostic performance of the American Joint Committee on Cancer 8th edition of the TNM staging system in patients with early oral tongue cancer","volume":"41","author":"Amit","year":"2019","journal-title":"Head Neck"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.bjoms.2018.01.017","article-title":"Is the 8th edition of the Union for International Cancer Control staging of oral cancer good enough?","volume":"56","author":"Vuity","year":"2018","journal-title":"Br. J. Oral Maxillofac. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1111\/odi.13194","article-title":"Tumor depth of invasion and prognosis of early-stage oral squamous cell carcinoma: A meta-analysis","volume":"26","author":"Caldeira","year":"2020","journal-title":"Oral Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s00784-020-03421-2","article-title":"Staging more important than grading? Evaluation of malignancy grading, depth of invasion, and resection margins in oral squamous cell carcinoma","volume":"25","author":"Wunschel","year":"2021","journal-title":"Clin. Oral Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"104937","DOI":"10.1016\/j.oraloncology.2020.104937","article-title":"The 8th TNM classification for oral squamous cell carcinoma: What is gained, what is lost, and what is missing","volume":"111","author":"Mattavelli","year":"2020","journal-title":"Oral Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.oraloncology.2017.09.007","article-title":"Tumor thickness versus depth of invasion\u2014Analysis of the 8th edition American Joint Committee on Cancer Staging for oral cancer","volume":"74","author":"Dirven","year":"2017","journal-title":"Oral Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1002\/hed.21846","article-title":"Risks and clinical implications of perineural invasion in T1-2 oral tongue squamous cell carcinoma","volume":"34","author":"Tai","year":"2012","journal-title":"Head Neck"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1245\/s10434-011-2182-5","article-title":"Treatment for T1-2 oral squamous cell carcinoma with or without perineural invasion: Neck dissection and postoperative adjuvant therapy","volume":"19","author":"Tai","year":"2012","journal-title":"Ann. Surg. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.tripleo.2003.10.014","article-title":"Prognostic significance of perineural invasion in oral and oropharyngeal carcinoma","volume":"97","author":"Rahima","year":"2004","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.1245\/s10434-013-3068-5","article-title":"Perineural invasion as a major determinant for the aggressiveness associated with increased tumor thickness in t1-2 oral tongue and buccal squamous cell carcinoma","volume":"20","author":"Tai","year":"2013","journal-title":"Ann. Surg. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.oraloncology.2008.03.009","article-title":"The impact of lymphovascular invasion on survival in oral carcinoma","volume":"45","author":"Jones","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.ijom.2004.10.006","article-title":"Factors affecting survival in patients with oral cancer: An Australian perspective","volume":"34","author":"Chandu","year":"2005","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1001\/jamaoto.2016.3795","article-title":"Association of Lymphovascular Space Invasion With Locoregional Failure and Survival in Patients With Node-Negative Oral Tongue Cancers","volume":"143","author":"Cassidy","year":"2017","journal-title":"JAMA Otolaryngol. Head Neck Surg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1001\/jama.1920.02620100016007","article-title":"Squamous cell epithelioma of the lip. A study of five hundred and thirty-seven cases","volume":"74","author":"Broders","year":"1920","journal-title":"JAMA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.1600-0714.2009.00751.x","article-title":"Malignancy grading is no better than conventional histopathological grading in small squamous cell carcinoma of tongue and floor of mouth: Retrospective study in 128 patients","volume":"38","author":"Weijers","year":"2009","journal-title":"J. Oral Pathol. Med."},{"key":"ref_61","first-page":"e603","article-title":"Oral squamous cell carcinoma of tongue: Histological risk assessment. A pilot study","volume":"24","year":"2019","journal-title":"Med. Oral Patol. Oral Cir. Bucal."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/S0046-8177(86)80457-9","article-title":"Prognostic factors in squamous cell carcinoma of the lower lip","volume":"17","author":"Frierson","year":"1986","journal-title":"Hum. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"104706","DOI":"10.1016\/j.oraloncology.2020.104706","article-title":"Tumor histologic grade as a risk factor for neck recurrence in patients with T1-2N0 early tongue cancer","volume":"106","author":"Chuang","year":"2020","journal-title":"Oral Oncol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/19\/4882\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:02:58Z","timestamp":1760130178000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/19\/4882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,8]]},"references-count":63,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["cancers15194882"],"URL":"https:\/\/doi.org\/10.3390\/cancers15194882","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,8]]}}}