Skip to main content

Current Updates in Staging and Prognosis in Oral Cancer

  • Chapter
  • First Online:
  • 493 Accesses

Abstract

Purpose of review: In this update, data supporting the recent changes to the eighth edition of the AJCC staging system for oral squamous cell carcinoma, as well as other important prognostic considerations, will be presented.

Recent findings: Depth of invasion ≥4 mm and the presence of extranodal extension are independent factors that negatively impact locoregional control and survival. Computed tomography and magnetic resonance imaging have a low sensitivity, but high specificity in detecting extranodal extension. Sentinel lymph node biopsy may prove useful in oral squamous cell carcinoma with a detection rate of 98%, sensitivity of 92%, and specificity of 100%. Close resection margins of <5 mm maintain a local control rate of 91% and disease-specific survival of 84%, regardless of additional adverse tumor features. Perineural invasion, lymphovascular invasion, infiltrative patterns of invasion, and high lymph node ratios have been associated with locoregional recurrence and mortality. HPV seems to play a minor role in the oncogenesis of oral squamous cell carcinoma.

Summary: In the latest edition of the cancer staging system by the AJCC, depth of invasion and extranodal extension are used to further define staging categories. The T stage increases by one for every 5 mm of tumor DOI until ≥10 mm and the pathologic N stage increases by one with ENE. Changes better correlate to locoregional control and survival. Adverse features and tumor burden must also be considered when optimizing treatment protocols.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Ridge JA, Lydiatt WM, Patel SG, Glastonbury CM, Brandwein-Gensler MS, Ghossein RA, et al. Lip and oral cavity. In: Amin MB, editor. AJCC cancer staging manual. 8th ed. NewYork, NY: Springer; 2017. p. 79–94.

    Chapter  Google Scholar 

  2. Tirelli G, Gatto A, Boscolo Nata F, Bussani R, Piccinato A, Marcuzzo AV, et al. 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. Br J Oral Maxillofac Surg. 2018;56(1):8–13.

    Article  PubMed  Google Scholar 

  3. Ebrahimi A, Gil Z, Amit M, Yen TC, Liao CT, Chaturvedi P, et al. Primary tumor staging for oral cancer and a proposed modification incorporating depth of invasion: an international multicenter retrospective study. JAMA Otolaryngol Head Neck Surg. 2014;140(12):1138–48.

    Article  PubMed  Google Scholar 

  4. Almangush A, Leivo I, Siponen M, Sundquist E, Mroueh R, Makitie AA, et al. Evaluation of the budding and depth of invasion (BD) model in oral tongue cancer biopsies. Virchows Archiv. 2018;472(2):231–6.

    Article  PubMed  Google Scholar 

  5. Tan WJ, Chia CS, Tan HK, Soo KC, Iyer NG. Prognostic significance of invasion depth in oral tongue squamous cell carcinoma. ORL. 2012;74(5):264–70.

    Article  PubMed  Google Scholar 

  6. Almangush A, Bello IO, Coletta RD, Makitie AA, Makinen LK, Kauppila JH, et al. For early-stage oral tongue cancer, depth of invasion and worst pattern of invasion are the strongest pathological predictors for locoregional recurrence and mortality. Virchows Archiv. 2015;467(1):39–46.

    Article  PubMed  Google Scholar 

  7. Brockhoff HC 2nd, Kim RY, Braun TM, Skouteris C, Helman JI, Ward BB. Correlating the depth of invasion at specific anatomic locations with the risk for regional metastatic disease to lymph nodes in the neck for oral squamous cell carcinoma. Head Neck. 2017;39(5):974–9.

    Article  PubMed  Google Scholar 

  8. Arora A, Husain N, Bansal A, Neyaz A, Jaiswal R, Jain K, et al. Development of a new outcome prediction model in early-stage squamous cell carcinoma of the oral cavity based on histopathologic parameters with multivariate analysis: the Aditi-Nuzhat Lymph-node Prediction Score (ANLPS) system. Am J Surg Pathol. 2017;41(7):950–60.

    Article  PubMed  Google Scholar 

  9. Li C, Lin J, Men Y, Yang W, Mi F, Li L. Does medullary versus cortical invasion of the mandible affect prognosis in patients with oral squamous cell carcinoma? J Oral Maxillofac Surg. 2017;75(2):403–15.

    Article  PubMed  Google Scholar 

  10. Fives C, Nae A, Roche P, O'Leary G, Fitzgerald B, Feeley L, et al. Impact of mandibular invasion on prognosis in oral squamous cell carcinoma four centimeters or less in size. Laryngoscope. 2017;127(4):849–54.

    Article  PubMed  Google Scholar 

  11. Almulla A, Noel CW, Lu L, Xu W, O'Sullivan B, Goldstein DP, et al. Radiologic-pathologic correlation of extranodal extension in patients with squamous cell carcinoma of the oral cavity: implications for future editions of the TNM classification. Int J Radiat Oncol Biol Phys. 2018;102(4):698–708.

    Article  PubMed  Google Scholar 

  12. Carlton JA, Maxwell AW, Bauer LB, McElroy SM, Layfield LJ, Ahsan H, et al. Computed tomography detection of extracapsular spread of squamous cell carcinoma of the head and neck in metastatic cervical lymph nodes. Neuroradiol J. 2017;30(3):222–9.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lewis JS Jr, Carpenter DH, Thorstad WL, Zhang Q, Haughey BH. Extracapsular extension is a poor predictor of disease recurrence in surgically treated oropharyngeal squamous cell carcinoma. Modern Pathol. 2011;24(11):1413–20.

    Article  Google Scholar 

  14. Suton P, Salaric I, Granic M, Mueller D, Luksic I. Prognostic significance of extracapsular spread of lymph node metastasis from oral squamous cell carcinoma in the clinically negative neck. Int J Oral Maxillofac Surg. 2017;46(6):669–75.

    Article  PubMed  Google Scholar 

  15. Jose J, Coatesworth AP, Johnston C, MacLennan K. Cervical node metastases in squamous cell carcinoma of the upper aerodigestive tract: the significance of extracapsular spread and soft tissue deposits. Head Neck. 2003;25(6):451–6.

    Article  PubMed  Google Scholar 

  16. Ho AS, Kim S, Tighiouart M, Gudino C, Mita A, Scher KS, et al. Metastatic lymph node burden and survival in oral cavity cancer. J Clin Oncol. 2017;35(31):3601–9.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Matos LL, Dedivitis RA, Kulcsar MAV, de Mello ES, Alves VAF, Cernea CR. External validation of the AJCC cancer staging manual, 8th edition, in an independent cohort of oral cancer patients. Oral Oncol. 2017;71:47–53.

    Article  PubMed  Google Scholar 

  18. Mermod M, Tolstonog G, Simon C, Monnier Y. Extracapsular spread in head and neck squamous cell carcinoma: a systematic review and meta-analysis. Oral Oncol. 2016;62:60–71.

    Article  PubMed  Google Scholar 

  19. Buchakjian MR, Tasche KK, Robinson RA, Pagedar NA, Sperry SM. Association of main specimen and tumor bed margin status with local recurrence and survival in oral cancer surgery. JAMA Otolaryngol Head Neck Surg. 2016;142(12):1191–8.

    Article  PubMed  Google Scholar 

  20. Maxwell JH, Thompson LD, Brandwein-Gensler MS, Weiss BG, Canis M, Purgina B, et al. Early oral tongue squamous cell carcinoma: sampling of margins from tumor bed and worse local control. JAMA Otolaryngol Head Neck Surg. 2015;141(12):1104–10.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Mair M, Nair D, Nair S, Dutta S, Garg A, Malik A, et al. Intraoperative gross examination vs frozen section for achievement of adequate margin in oral cancer surgery. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;123(5):544–9.

    Article  PubMed  Google Scholar 

  22. Nieberler M, Haussler P, Kesting MR, Kolk A, Deppe H, Weirich G, et al. Clinical impact of intraoperative cytological assessment of bone resection margins in patients with head and neck carcinoma. Ann Surg Oncol. 2016;23(11):3579–86.

    Article  PubMed  Google Scholar 

  23. Meier JD, Oliver DA, Varvares MA. Surgical margin determination in head and neck oncology: current clinical practice. the results of an International American Head and Neck Society Member Survey. Head Neck. 2005;27(11):952–8.

    Article  PubMed  Google Scholar 

  24. Ch'ng S, Corbett-Burns S, Stanton N, Gao K, Shannon K, Clifford A, et al. Close margin alone does not warrant postoperative adjuvant radiotherapy in oral squamous cell carcinoma. Cancer. 2013;119(13):2427–37.

    Article  PubMed  Google Scholar 

  25. Buchakjian MR, Ginader T, Tasche KK, Pagedar NA, Smith BJ, Sperry SM. Independent predictors of prognosis based on oral cavity squamous cell carcinoma surgical margins. Otolaryngol Head Neck Surg. 2018;2018:194599818773070.

    Google Scholar 

  26. Ross MI, Reintgen D, Balch CM. Selective lymphadenectomy: emerging role for lymphatic mapping and sentinel node biopsy in the management of early stage melanoma. Semin Surg Oncol. 1993;9(3):219–23.

    PubMed  Google Scholar 

  27. Yang Y, Zhou J, Wu H. Diagnostic value of sentinel lymph node biopsy for cT1/T2N0 tongue squamous cell carcinoma: a meta-analysis. Eur Archiv Oto-rhino-laryngol. 2017;274(11):3843–52.

    Article  Google Scholar 

  28. Lin R, Yan J, Liu W, Fan T, Tang L. The predictive value of cervical lymph node metastasis through sentinel lymph node biopsy in patients with oral cancer: a meta-analysis. J Cancer Res Ther. 2016;12(Suppl):C256–c9.

    PubMed  Google Scholar 

  29. Schilling C, Stoeckli SJ, Haerle SK, Broglie MA, Huber GF, Sorensen JA, et al. Sentinel European Node Trial (SENT): 3-year results of sentinel node biopsy in oral cancer. Eur J Cancer. 2015;51(18):2777–84.

    Article  PubMed  Google Scholar 

  30. Civantos FJ, Zitsch RP, Schuller DE, Agrawal A, Smith RB, Nason R, 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):1395–400.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Miura K, Hirakawa H, Uemura H, Yoshimoto S, Shiotani A, Sugasawa M, et al. Sentinel node biopsy for oral cancer: a prospective multicenter Phase II trial. Auris Nasus Larynx. 2017;44(3):319–26.

    Article  PubMed  Google Scholar 

  32. Liebig C, Ayala G, Wilks JA, Berger DH, Albo D. Perineural invasion in cancer: a review of the literature. Cancer. 2009;115(15):3379–91.

    Article  PubMed  Google Scholar 

  33. Tai SK, Li WY, Chu PY, Chang SY, Tsai TL, Wang YF, et al. Risks and clinical implications of perineural invasion in T1-2 oral tongue squamous cell carcinoma. Head Neck. 2012;34(7):994–1001.

    Article  PubMed  Google Scholar 

  34. Jardim JF, Francisco AL, Gondak R, Damascena A, Kowalski LP. Prognostic impact of perineural invasion and lymphovascular invasion in advanced stage oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2015;44(1):23–8.

    Article  PubMed  Google Scholar 

  35. Chatzistefanou I, Lubek J, Markou K, Ord RA. The role of neck dissection and postoperative adjuvant radiotherapy in cN0 patients with PNI-positive squamous cell carcinoma of the oral cavity. Oral Oncol. 2014;50(8):753–8.

    Article  PubMed  Google Scholar 

  36. Bur AM, Lin A, Weinstein GS. Adjuvant radiotherapy for early head and neck squamous cell carcinoma with perineural invasion: a systematic review. Head Neck. 2016;38(Suppl 1):E2350–7.

    Article  PubMed  Google Scholar 

  37. Liu T, Chua B, Batstone M. Postoperative radiotherapy for oral squamous cell carcinoma with histologic risk factors: are we over-treating? J Oral Maxillofac Surg. 2018;76(7):1565–70.

    Article  PubMed  Google Scholar 

  38. Cassidy RJ, Switchenko JM, Jegadeesh N, Sayan M, Ferris MJ, Eaton BR, et al. Association of lymphovascular space invasion with locoregional failure and survival in patients with node-negative oral tongue cancers. JAMA Otolaryngol Head Neck Surg. 2017;143(4):382–8.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Fives C, Feeley L, O'Leary G, Sheahan P. Importance of lymphovascular invasion and invasive front on survival in floor of mouth cancer. Head Neck. 2016;38(Suppl 1):E1528–34.

    Article  PubMed  Google Scholar 

  40. Hosni A, McMullen C, Huang SH, Xu W, Su J, Bayley A, et al. Lymph node ratio relationship to regional failure and distant metastases in oral cavity cancer. Radiother Oncol. 2017;124(2):225–31.

    Article  PubMed  Google Scholar 

  41. Bishop JA, Lewis JS Jr, Rocco JW, Faquin WC. HPV-related squamous cell carcinoma of the head and neck: An update on testing in routine pathology practice. Semin Diagn Pathol. 2015;32(5):344–51.

    Article  PubMed  Google Scholar 

  42. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Wang F, Zhang H, Xue Y, Wen J, Zhou J, Yang X, et al. A systematic investigation of the association between HPV and the clinicopathological parameters and prognosis of oral and oropharyngeal squamous cell carcinomas. Cancer Med. 2017;6(5):910–7.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Westra WH. Detection of human papillomavirus (HPV) in clinical samples: evolving methods and strategies for the accurate determination of HPV status of head and neck carcinomas. Oral Oncol. 2014;50(9):771–9.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Mirghani H, Amen F, Moreau F, Lacau St Guily J. Do high-risk human papillomaviruses cause oral cavity squamous cell carcinoma? Oral Oncol. 2015;51(3):229–36.

    Article  PubMed  Google Scholar 

  46. Thomas J, Primeaux T. Is p16 immunohistochemistry a more cost-effective method for identification of human papilloma virus-associated head and neck squamous cell carcinoma? Ann Diagn Pathol. 2012;16(2):91–9.

    Article  PubMed  Google Scholar 

  47. Miller CS, Johnstone BM. Human papillomavirus as a risk factor for oral squamous cell carcinoma: a meta-analysis, 1982-1997. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91(6):622–35.

    Article  PubMed  Google Scholar 

  48. Kansy K, Thiele O, Freier K. The role of human papillomavirus in oral squamous cell carcinoma: myth and reality. Oral Maxillofac Surg. 2014;18(2):165–72.

    Article  PubMed  Google Scholar 

  49. Poling JS, Ma XJ, Bui S, Luo Y, Li R, Koch WM, et al. Human papillomavirus (HPV) status of non-tobacco related squamous cell carcinomas of the lateral tongue. Oral Oncol. 2014;50(4):306–10.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Harris SL, Thorne LB, Seaman WT, Hayes DN, Couch ME, Kimple RJ. Association of p16(INK4a) overexpression with improved outcomes in young patients with squamous cell cancers of the oral tongue. Head Neck. 2011;33(11):1622–7.

    Article  PubMed  Google Scholar 

  51. Lingen MW, Xiao W, Schmitt A, Jiang B, Pickard R, Kreinbrink P, et al. Low etiologic fraction for high-risk human papillomavirus in oral cavity squamous cell carcinomas. Oral Oncol. 2013;49(1):1–8.

    Article  PubMed  Google Scholar 

  52. Kruger M, Pabst AM, Walter C, Sagheb K, Gunther C, Blatt S, et al. The prevalence of human papilloma virus (HPV) infections in oral squamous cell carcinomas: a retrospective analysis of 88 patients and literature overview. J Cranio-maxillo-fac Surg. 2014;42(7):1506–14.

    Article  Google Scholar 

  53. Bryne M, Koppang HS, Lilleng R, Kjaerheim A. Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value. J Pathol. 1992;166(4):375–81.

    Article  PubMed  Google Scholar 

  54. Brandwein-Gensler M, Teixeira MS, Lewis CM, Lee B, Rolnitzky L, Hille JJ, et al. Oral squamous cell carcinoma: histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival. Am J Surg Pathol. 2005;29(2):167–78.

    Article  PubMed  Google Scholar 

  55. Safi AF, Grandoch A, Nickenig HJ, Zoller JE, Kreppel M. The importance of lymph node ratio for locoregional recurrence of squamous cell carcinoma of the tongue. J Cranio-maxillo-fac Surg. 2017;45(7):1058–61.

    Article  Google Scholar 

  56. Safi AF, Grandoch A, Nickenig HJ, Zoller JE, Kreppel M. Importance of lymph node ratio for locoregional recurrence of squamous cell carcinoma of the buccal mucosa. Head Neck. 2017;39(12):2488–93.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Photomicrograph in Fig. 4.2 by Ashley Flowers, MD—Assistant Professor, Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA.

Conflicts of interest: There are no conflicts of interest to report.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. David Kim .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Covello, P., Kim, D.D. (2020). Current Updates in Staging and Prognosis in Oral Cancer. In: Kademani, D. (eds) Improving Outcomes in Oral Cancer. Springer, Cham. https://doi.org/10.1007/978-3-030-30094-4_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-30094-4_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-30093-7

  • Online ISBN: 978-3-030-30094-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics