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The management of oral cancer – current standards and future perspectives. Review of the literature

Natalia Amrogowicz1, Tomasz Rutkowski2


Oral cancer (OC) is one of the most common cancers of the head and neck region, with approximately 1,950 new cases reported in Poland in 2019. The main factors contributing to the development of OC are cigarette smoking and excessive alcohol consumption. Squamous cell carcinoma accounts for more than 90% of all OCs. In patients with OC surgery is the treatment of choice, but there is a high number of patients who require complementary treatment – radiotherapy or radiochemotherapy. The treatment of these tumours should be comprehensive and multidisciplinary. Due to suboptimal treatment outcomes in this patient group, numerous clinical trials are being conducted to search for new, more effective treatments. The aim of this study was to review the literature on current and new methods of diagnosis and treatment of OC and to analyse the clinical trials currently available for OC patients in Poland. Despite the use of modern drugs, only modest progress has been made in terms of treatment efficacy.

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  1. WHO, Cancer Today, Raport 2020.
  2. Krajowy Rejestr Nowotworów.
  3. Blot WJ, McLaughlin JK, Winn DM, et al. Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res. 1988; 48(11): 3282–3287.
  4. International Agency on Research for Cancer. Smokeless Tobacco and Some Tobacco-specific N-Nitrosamines. Monographs Vol. 89. IARC, Lyon 2007.
  5. Warnakulasuriya S, Sutherland G, Scully C. Tobacco, oral cancer, and treatment of dependence. Oral Oncol. 2005; 41(3): 244–260.
  6. Scully C. Oral cancer aethiopathogenesis; past, present and future aspects. Med Oral Patol Oral Cir Bucal. 2011; 16(3): e306–e311.
  7. Wen CP, Tsai MK, Chung WS, et al. Cancer risks from betel quid chewing beyond oral cancer: a multiple-site carcinogen when acting with smoking. Cancer Causes Control. 2010; 21(9): 1427–1435.
  8. D'Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007; 356(19): 1944–1956.
  9. Herrero R, Castellsagué X, Pawlita M, et al. IARC Multicenter Oral Cancer Study Group. Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study. J Natl Cancer Inst. 2003; 95(23): 1772–1783.
  10. Biesaga B, Smolarczyk R, Mucha-Małecka A, et al. Prognostic Significance of STING Immunoexpression in Relation to HPV16 Infection in Patients with Squamous Cell Carcinomas of Oral Cavity and Oropharynx. Biomedicines. 2022; 10(10).
  11. 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): 622–635.
  12. Shillitoe EJ. The role of viruses in squamous cell carcinoma of the oropharyngeal mucosa. Oral Oncol. 2009; 45(4-5): 351–355.
  13. Sulkowska U, Mańczuk M, Przewoźniak K, et al. Estimating of the number of cancer cases attributed to HPV infections for Poland in 2015. Nowotwory. Journal of Oncology. 2018; 68(4): 173–175.
  14. Popović B, Jekić B, Novaković I, et al. Cancer genes alterations and HPV infection in oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2010; 39(9): 909–915.
  15. Eglin RP, Scully C, Lehner T, et al. Detection of RNA complementary to herpes simplex virus in human oral squamous cell carcinoma. Lancet. 1983; 2(8353): 766–768.
  16. Shillitoe EJ. The role of viruses in squamous cell carcinoma of the oropharyngeal mucosa. Oral Oncol. 2009; 45(4-5): 351–355.
  17. Zheng Y, Xia Pu, Zheng HC, et al. The screening of viral risk factors in tongue and pharyngolaryngeal squamous carcinoma. Anticancer Res. 2010; 30(4): 1233–1238.
  18. Bagan JV, Jiménez Y, Murillo J, et al. Epstein-Barr virus in oral proliferative verrucous leukoplakia and squamous cell carcinoma: A preliminary study. Med Oral Patol Oral Cir Bucal. 2008; 13(2): E110–E113.
  19. Jalouli J, Ibrahim SO, Mehrotra R, et al. Prevalence of viral (HPV, EBV, HSV) infections in oral submucous fibrosis and oral cancer from India. Acta Otolaryngol. 2010; 130(11): 1306–1311.
  20. Laborde RR, Novakova V, Olsen KD, et al. Expression profiles of viral responsive genes in oral and oropharyngeal cancers. Eur J Cancer. 2010; 46(6): 1153–1158.
  21. Yen CY, Lu MC, Tzeng CC, et al. Detection of EBV infection and gene expression in oral cancer from patients in Taiwan by microarray analysis. J Biomed Biotechnol. 2009; 2009: 904589.
  22. Kis A, Fehér E, Gáll T, et al. Epstein-Barr virus prevalence in oral squamous cell cancer and in potentially malignant oral disorders in an eastern Hungarian population. Eur J Oral Sci. 2009; 117(5): 536–540.
  23. Fitzpatrick SG, Katz J. The association between periodontal disease and cancer: a review of the literature. J Dent. 2010; 38(2): 83–95.
  24. Yamazaki H, Inoue T, Yoshida K, et al. Assessment of influence of smoking, drinking, leukoplakia and dental irritation on local control of early oral tongue carcinoma treated with brachytherapy: age and dental factors are potential prognostic factors. Tumori. 2009; 95(4): 461–466.
  25. Freedman ND, Park Y, Subar AF, et al. Fruit and vegetable intake and head and neck cancer risk in a large United States prospective cohort study. Int J Cancer. 2008; 122(10): 2330–2336.
  26. Bosetti C, Gallus S, Trichopoulou A, et al. Influence of the Mediterranean diet on the risk of cancers of the upper aerodigestive tract. Cancer Epidemiol Biomarkers Prev. 2003; 12(10): 1091–1094.
  27. Sakthivel P, Raveendran S, Panda S, et al. Oral potential malignant disorders - A long list not to be forgotten. Oral Oncol. 2021; 116: 105244.
  28. Prime SS, Thakker NS, Pring M, et al. A review of inherited cancer syndromes and their relevance to oral squamous cell carcinoma. Oral Oncol. 2001; 37(1): 1–16.
  29. Irani S. Pre-Cancerous Lesions in the Oral and Maxillofacial Region: A Literature Review with Special Focus on Etiopathogenesis. Iran J Pathol. 2016; 11(4): 303–322.
  30. Khan MM, Frustino J, Villa A, et al. Total RNA sequencing reveals gene expression and microbial alterations shared by oral pre-malignant lesions and cancer. Hum Genomics. 2023; 17(1): 72.
  31. Rivera C. Essentials of oral cancer. Int J Clin Exp Pathol. 2015; 8(9): 11884–11894.
  32. Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009; 45(4-5): 309–316.
  33. Wierzbicka M. Nowotwory jamy ustnej. In: Szyfter W. ed. Nowotwory w otolaryngologii wyd. II. Termedia, Poznań 2015: 177–211.
  34. Ettinger KS, Ganry L, Fernandes RP. Oral Cavity Cancer. Oral Maxillofac Surg Clin North Am. 2019; 31(1): 13–29.
  35. Shah JP, Gil Z. Current concepts in management of oral cancer--surgery. Oral Oncol. 2009; 45(4-5): 394–401.
  36. Lo WL, Kao SY, Chi LY, et al. Outcomes of oral squamous cell carcinoma in Taiwan after surgical therapy: factors affecting survival. J Oral Maxillofac Surg. 2003; 61(7): 751–758.
  37. Byers RM, El-Naggar AK, Lee YY, et al. Can we detect or predict the presence of occult nodal metastases in patients with squamous carcinoma of the oral tongue? Head Neck. 1998; 20(2): 138–144, doi: 10.1002/(sici)1097-0347(199803)20:2<138::aid-hed7>;2-3.
  38. Shah J, Candela F, Poddar A. 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>;2-a.
  39. Massey C, Dharmarajan A, Bannuru RR, et al. Management of N0 neck in early oral squamous cell carcinoma: A systematic review and meta-analysis. Laryngoscope. 2019; 129(8): E284–E298.
  40. Haseeb AA, Rahim AUr, Iqbal S, et al. The frequency of occult cervical metastasis in oral squamous cell carcinoma patients - A cross sectional study. J Pak Med Assoc. 2022; 72(1): 66–70.
  41. Byers RM, Weber RS, Andrews T, et al. Frequency and therapeutic implications of "skip metastases" in the neck from squamous carcinoma of the oral tongue. Head Neck. 1997; 19(1): 14–19, doi: 10.1002/(sici)1097-0347(199701)19:1<14::aid-hed3>;2-y.
  42. Koyfman SA, Ismaila N, Crook D, et al. Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline. J Clin Oncol. 2019; 37(20): 1753–1774.
  43. Paleri V, Urbano TG, Mehanna H, et al. Management of neck metastases in head and neck cancer: United Kingdom National Multidisciplinary Guidelines. J Laryngol Otol. 2016; 130(S2): S161–S169.
  44. Fridman E, Na'ara S, Agarwal J, et al. International Consortium for Outcome Research in Head and Neck Cancer. The role of adjuvant treatment in early-stage oral cavity squamous cell carcinoma: An international collaborative study. Cancer. 2018; 124(14): 2948–2955.
  45. Chen WC, Lai CH, Fang CC, et al. Identification of High-Risk Subgroups of Patients With Oral Cavity Cancer in Need of Postoperative Adjuvant Radiotherapy or Chemo-Radiotherapy. Medicine (Baltimore). 2016; 95(22): e3770.
  46. Amin MB, Edge S, Greene F, et al. AJCC cancer staging manual. Eight edition. Springer 2017.
  47. Fukano H, Matsuura H, Hasegawa Y, et al. Depth of invasion as a predictive factor for cervical lymph node metastasis in tongue carcinoma. Head Neck. 1997; 19(3): 205–210, doi: 10.1002/(sici)1097-0347(199705)19:3<205::aid-hed7>;2-6.
  48. Bànkfalvi A, Piffkò J. Prognostic and predictive factors in oral cancer: the role of the invasive tumour front. J Oral Pathol Med. 2000; 29(7): 291–298.
  49. Yamauchi M, Ishida T, Minesaki A, et al. WPOI-4/5 Correlates With Lymph Node Recurrence and Poor Prognosis in Early-stage Tongue Squamous Cell Carcinoma. Cancer Diagn Progn. 2023; 3(4): 457–462.
  50. Brandwein-Gensler M, Teixeira MS, Lewis CM, 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): 167–178.
  51. Boxberg M, Bollwein C, Jöhrens K, et al. Novel prognostic histopathological grading system in oral squamous cell carcinoma based on tumour budding and cell nest size shows high interobserver and intraobserver concordance. J Clin Pathol. 2019; 72(4): 285–294.
  52. Ragin CCR, Taioli E. Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: review and meta-analysis. Int J Cancer. 2007; 121(8): 1813–1820.
  53. Miranda-Galvis M, Rumayor Piña A, Sales de Sá R, et al. PD-L1 expression patterns in oral cancer as an integrated approach for further prognostic classification. Oral Dis. 2021; 27(7): 1699–1710.
  54. Bauml J, Seiwert TY, Pfister DG, et al. Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study. J Clin Oncol. 2017; 35(14): 1542–1549.
  55. Cramer JD, Burtness B, Ferris RL. Immunotherapy for head and neck cancer: Recent advances and future directions. Oral Oncol. 2019; 99: 104460.
  56. Snietura M, Jaworska M, Mlynarczyk-Liszka J, et al. PTEN as a prognostic and predictive marker in postoperative radiotherapy for squamous cell cancer of the head and neck. PLoS One. 2012; 7(3): e33396.
  57. Strzelczyk JK, Krakowczyk Ł, Gołąbek K, et al. Expression profiles of selected genes in tumors and matched surgical margins in oral cavity cancer: Do we have to pay attention to the molecular analysis of the surgical margins? Adv Clin Exp Med. 2018; 27(6): 833–840.
  58. Lei Yu, Xie Y, Tan YS, et al. Telltale tumor infiltrating lymphocytes (TIL) in oral, head & neck cancer. Oral Oncol. 2016; 61: 159–165.
  59. Maiti GP, Mondal P, Mukherjee N, et al. Overexpression of EGFR in head and neck squamous cell carcinoma is associated with inactivation of SH3GL2 and CDC25A genes. PLoS One. 2013; 8(5): e63440.
  60. Schena M, Guarrera S, Buffoni L, et al. DNA repair gene expression level in peripheral blood and tumour tissue from non-small cell lung cancer and head and neck squamous cell cancer patients. DNA Repair (Amst). 2012; 11(4): 374–380.
  61. Wróbel-Roztropiński A, Zielińska-Kaźmierska B, Roztropiński H, et al. Expression of matrix metalloproteinases (MMPs) and their inhibitor (TIMP) genes on mRNA and protein levels in oral squamous cell carcinoma. Nowotwory. Journal of Oncology. 2021; 71(1): 1–8.
  62. Peters LJ, Goepfert H, Ang KK, et al. Evaluation of the dose for postoperative radiation therapy of head and neck cancer: first report of a prospective randomized trial. Int J Radiat Oncol Biol Phys. 1993; 26(1): 3–11.
  63. Ang KK, Trotti A, Brown BW, et al. Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2001; 51(3): 571–578.
  64. Bernier J, Domenge C, Ozsahin M, et al. European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004; 350(19): 1945–1952.
  65. Cooper JS, Pajak TF, Forastiere AA, et al. Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004; 350(19): 1937–1944.
  66. Pfister DG, Spencer S, Adkins D, et al. Head and Neck Cancers, Version 2.2023. NCCN Clinical Practice Guidelines in Oncology .
  67. Sumioka S, Sawai NY, Kishino M, et al. Risk factors for distant metastasis in squamous cell carcinoma of the oral cavity. J Oral Maxillofac Surg. 2013; 71(7): 1291–1297.
  68. Rosenthal DI, Mohamed ASR, Garden AS, et al. Final Report of a Prospective Randomized Trial to Evaluate the Dose-Response Relationship for Postoperative Radiation Therapy and Pathologic Risk Groups in Patients With Head and Neck Cancer. Int J Radiat Oncol Biol Phys. 2017; 98(5): 1002–1011.
  69. Langendijk JA, de Jong MA, Leemans CR, et al. Postoperative radiotherapy in squamous cell carcinoma of the oral cavity: the importance of the overall treatment time. Int J Radiat Oncol Biol Phys. 2003; 57(3): 693–700.
  70. Rosenthal DI, Liu Li, Lee JH, et al. Importance of the treatment package time in surgery and postoperative radiation therapy for squamous carcinoma of the head and neck. Head Neck. 2002; 24(2): 115–126.
  71. Mucha-Małecka A, Składowski K, Lange D. Histopathological factors influencing results of combined treatment in patients with laryngeal cancer. Pol J Pathol. 2015; 66(3): 260–268.
  72. Snyderman NL, Johnson JT, Schramm VL, et al. Extracapsular spread of carcinoma in cervical lymph nodes. Impact upon survival in patients with carcinoma of the supraglottic larynx. Cancer. 1985; 56(7): 1597–1599, doi: 10.1002/1097-0142(19851001)56:7<1597::aid-cncr2820560722>;2-5.
  73. Bachaud JM, Cohen-Jonathan E, Alzieu C, et al. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Int J Radiat Oncol Biol Phys. 1996; 36(5): 999–1004.
  74. Skóra T, Nowak-Sadzikowska J, Mucha-Małecka A, et al. Postoperative irradiation in patients with pT3-4N0 laryngeal cancer: results and prognostic factors. Eur Arch Otorhinolaryngol. 2015; 272(3): 673–679.
  75. Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005; 27(10): 843–850.
  76. Rutkowski T, Wygoda A, Hutnik M, et al. Intraoperative radiotherapy (IORT) with low-energy photons as a boost in patients with early-stage oral cancer with the indications for postoperative radiotherapy : treatment feasibility and preliminary results. Strahlenther Onkol. 2010; 186(9): 496–501.
  77. Chamoli A, Gosavi AS, Shirwadkar UP, et al. Overview of oral cavity squamous cell carcinoma: Risk factors, mechanisms, and diagnostics. Oral Oncol. 2021; 121: 105451.
  78. de Oliveira TB, Marta GN, de Castro Junior G, et al. Induction Chemotherapy for Advanced Oral Cavity Cancer. Curr Oncol Rep. 2021; 23(11): 129.
  79. Licitra L, Grandi C, Guzzo M, et al. Primary chemotherapy in resectable oral cavity squamous cell cancer: a randomized controlled trial. J Clin Oncol. 2003; 21(2): 327–333.
  80. Marta 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.
  83. Tam S, Araslanova R, Low THH, et al. Estimating Survival After Salvage Surgery for Recurrent Oral Cavity Cancer. JAMA Otolaryngol Head Neck Surg. 2017; 143(7): 685–690.
  84. Tian Z, Wang S, Xia R, et al. Salvage Surgery for Recurrent Tongue Cancer With Contralateral Neck Metastasis. J Oral Maxillofac Surg. 2021; 79(2): 490–500.
  85. Vargo JA, Ward MC, Caudell JJ, et al. A Multi-institutional Comparison of SBRT and IMRT for Definitive Reirradiation of Recurrent or Second Primary Head and Neck Cancer. Int J Radiat Oncol Biol Phys. 2018; 100(3): 595–605.
  86. Spencer SA, Harris J, Wheeler RH, et al. Final report of RTOG 9610, a multi-institutional trial of reirradiation and chemotherapy for unresectable recurrent squamous cell carcinoma of the head and neck. Head Neck. 2008; 30(3): 281–288.
  87. Langer CJ, Harris J, Horwitz EM, et al. Phase II study of low-dose paclitaxel and cisplatin in combination with split-course concomitant twice-daily reirradiation in recurrent squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Protocol 9911. J Clin Oncol. 2007; 25(30): 4800–4805.
  88. Matoscevic K, Graf N, Pezier TF, et al. Success of salvage treatment: a critical appraisal of salvage rates for different subsites of HNSCC. Otolaryngol Head Neck Surg. 2014; 151(3): 454–461.
  89. Gibson MK, Li Yi, Murphy B, et al. Eastern Cooperative Oncology Group. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): an intergroup trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2005; 23(15): 3562–3567.
  90. Colevas AD. Chemotherapy options for patients with metastatic or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2006; 24(17): 2644–2652.
  91. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008; 359(11): 1116–1127.
  92. Burtness B, Rischin D, Greil R, et al. Pembrolizumab Alone or With Chemotherapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma in KEYNOTE-048: Subgroup Analysis by Programmed Death Ligand-1 Combined Positive Score. J Clin Oncol. 2022; 40(21): 2321–2332.
  93. Ferris RL, Blumenschein G, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016; 375(19): 1856–1867.
  97. Palma DA, Olson RA, Harrow S, et al. Stereotactic Ablative Radiation Therapy for the Comprehensive Treatment of Oligometastatic Tumors (SABR-COMET): results of a randomized trial. Int J Radiat Oncol Biol Phys. 2018; 2013: S3–S4.
  98. Sun XuS, Michel C, Babin E, et al. Approach to oligometastatic disease in head and neck cancer, on behalf of the GORTEC. Future Oncol. 2018; 14(9): 877–889.
  99. Mohanti BK, Umapathy H, Bahadur S, et al. Short course palliative radiotherapy of 20 Gy in 5 fractions for advanced and incurable head and neck cancer: AIIMS study. Radiother Oncol. 2004; 71(3): 275–280.
  100. Fortin B, Khaouam N, Filion E, et al. Paliative radiation therapy for advanced head and neck carcinomas: a phase 2 study. Int J Radiat Oncol Biol Phys. 2016; 95(2): 647–653.

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