Skip to main content
NCBI home page
Indian Journal of Otolaryngology and Head & Neck Surgery logoLink to Indian Journal of Otolaryngology and Head & Neck Surgery
. 2023 Oct 3;76(1):626–632. doi: 10.1007/s12070-023-04230-1

Comparative Evaluation of Surgical Operability with and without Induction Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma

Haraprathap Yelishetty 1,✉, Jitendra Singh Yadav 1, Chandni Sethi 1, Rachna Chaurasia 1, Mayank Singh 1, Sachin Mahur 1, Shalini Tripathi 1, Bomkar Bam 1, Shraddha Gupta 1
PMCID: PMC10908765  PMID: 38440429

Abstract

To compare and evaluation of surgical operability with and without induction chemotherapy in locally advanced head and neck squamous cell carcinoma. Head and neck malignancy grossly refers to squamous cell carcinomas of head and neck (HNSCC) have multiple treatment modalities and strategies, when opted in an appropriate manner renders tumours curable. The aim of this study is to compare and evaluation of surgical operability with and without induction chemotherapy in locally advanced head and neck squamous cell carcinoma. A prospective observational study involving 50 patients of histologically proven squamous cell carcinoma of head and neck region. Patients were categorized into two major groups, group-1 patients included resectable tumour stage and group-2 included unresectable tumour stage. Both groups were compared after appropriate chemotherapy and surgical intervention. There were a total of 78% males and 22% females with majority of patients in age group of 41–60 years. 54% patients had ulcerative type of growth pattern and most patients had primary site of lesion in oral cavity. 50% patients had moderately differentiated squamous cell carcinoma. Induction chemotherapy was considered in 70% of patients, while majority of patients were belonging to T4N2M0 stage. In this study, we recommend that the borderline category of patients who are initially in an unresectable tumour stage can undergo induction chemotherapy to downstage and shrink the tumour to a resectable stage following which the appropriate surgical intervention should be done with a close monitoring and sustained follow up to prevent recurrence.

Keywords: Resectable and unresectable tumours, Head and neck squamous cell carcinoma, Induction chemotherapy, Surgical operability

Introduction

The term head and neck malignancy grossly refers to squamous cell carcinomas of head and neck (HNSCC), which are the most common cancers in developing countries, especially in Southeast Asia like India [1]. Overall, 57.5% of global head and neck cancers occur in Asia especially in India. Head and neck cancers in India account for 30% of all cancers [2, 3]. Over 2,00,000 cases of head and neck cancers occur each year in India. Nearly 80,000 oral cancers are diagnosed every year in our country [4]. Men are two to three times more commonly affected than women and the incidence among them increases with age around 98 percent of cases occurring in patients over 40 years of age.

The two most important factors in the etiology of head and neck cancer are tobacco and alcohol. There is a synergistic interaction between these two agents which is multiplicative for mouth, additive for the larynx [5]. Large case–control study from the United States shows good evidence of a dose–response relationship for both tobacco and alcohol [6, 7], other risk factors include use of areca nut, smoking and smokeless tobacco like khaini, mava, zarda, snuff etc, diet, occupational agents, pollutants and genetic profile influences the incidence. There is also a strong association between the subsite of oral cancer and the site where the tobacco is placed. In India and parts of Asia, oral tobacco is mixed with betel leaf, slaked lime and areca nut to form a quid called ‘paan’.

Head and neck malignancy of oral cavity and larynx are mostly squamous cell carcinomas, which gets evolved from flat squamous cells which make up the thin layer of tissue on the surface of structures in head and neck. Histologically, progression to invasive HNSCC follows an ordered series of steps beginning with epithelial cell hyperplasia, followed by dysplasia (mild, moderate and severe), carcinoma in situ and, ultimately, invasive carcinoma. However, in each case, normal adult stem or progenitor cells are likely candidates for the cell of origin, giving rise, following oncogenic transformation, to cancer stem cells (CSCs) with properties of self-renewal and pluripotency [8].

Chemotherapy alone cannot cure head and neck cancer, which should be used in conjunction with other treatments, like surgery and radiotherapy, to improve outcomes such as better local control, organ preservation with continued organ function and decrease the incidence of subclinical micrometastatic spread [9]. Locally advanced head and neck squamous cell carcinoma can be classified as resectable, borderline category (with a poor functional outcome) and unresectable categories whereas the borderline category of patients could benefit from an aggressive non-surgical approach instead of surgery [10]. Locally advanced unresectable oral squamous cell carcinoma is defined by the American Joint Committee on Cancer, 8th edition as the tumour invading the masticator space, pterygoid plates, skull base, or encasement of the internal carotid artery [11].

Patients who present with early clinical stages like stage 1 or stage 2 can be opted for any single mode of treatment with either chemotherapy alone or surgery for proper disease control and for good long term survival rates. But for patients who are presented with advanced clinical stages like stage 3 or stage 4, a multimodality approach of treatment may be required with surgery and /or radiotherapy, with or without chemotherapy.

Induction chemotherapy makes a possible strategy to shrink or downstage locally advanced head and neck cancers, which also increases the possibility of organ preservation, and/or to reduce the local and/or distant spread and recurrence, which ultimately improves treatment outcomes. It has to be kept in mind that even after induction chemotherapy, local surgical intervention has to be performed according to the original tumour borders, which should be marked accordingly before the commencement of treatment strategy [12].

Advantage of induction chemotherapy is that it includes early control of micrometastases, assessment of response to chemotherapy and rate of tumour regression which increases the chance of operability. Complete response (CR)-The disappearance of all known disease, determined by two observations not less than four weeks apart. Partial response (PR)- 50% or more decrease in total tumor load of the lesions that have been measured to determine the effect of therapy by two observations not less than four weeks apart. Bi-dimensional: single lesion, greater than or equal to 50% decrease in tumor area (multiplication of longest diameter by greatest perpendicular diameter); multiple lesions, a 50% decrease in sum of the products of perpendicular diameters of multiple lesions. Uni-dimensional: greater than or equal to 50% decrease in linear tumor measurement. In addition there can be no appearance of new lesions or progression of any lesion. No change (NC)- A 50% decrease in total tumor size cannot be established nor has a 25% increase in the size of one or more measurable lesions been demonstrated. Progressive disease (PD)- 25% or more increase in the size of one or more measurable lesions or the appearance of new lesions [13].

Materials and Methodology

The present study is tertiary care centre based and includes surgical operability with and without induction chemotherapy in locally advanced oral and laryngeal squamous cell carcinoma of both sex after obtaining the consent form from patients and relatives, with a minimum number of 50 patients selected for the study.

Inclusion Criteria

  • Histologically proven squamous cell carcinoma of head and neck region

  • Has a primary tumor location of oral cavity (lip, tongue, buccal mucosa, soft palate, hard palate, retromolar trigone, anterior pillar, gingivobuccal sulcus, teeth), or larynx.

  • Patients with resectable and underwent surgery and unresectable tumour stage

  • Patients who are fit to undergo chemotherapy

  • Informed consent

  • Age above 18 years

Exclusion Criteria

  • Patients not giving consent for the study

  • Patients with distant metastasis

  • Secondary malignancies

  • Patients with expected insufficient compliance

    Selected patients were subjected and evaluated with detailed history taking including present and past history and history of any previous illness and any relevant history noted followed by thorough clinical examination of the patients along with the investigations like routine blood investigations, biopsy of the lesion, FNAC, radiological investigations like Ultrasound along with contrast-enhanced computed tomography (CECT) of the head and neck and staged according to TNM classification. The clinical data given by patients were then complemented with information on diagnosis of the disease, the treatment administered (present and/or past), adverse effects reported (Figs. 1, 2, 3).

Fig. 1.

Fig. 1

Open in a new tab

Ulceroproliferative growth over left buccal mucosa with extension to left angle of mouth, wide local excision of primary tumour with supraomohyoid neck dissection with pectoralis major myocutaneous flap rotation was performed 

Fig. 2.

Fig. 2

Open in a new tab

Ulceroproliferative growth over left buccal mucosa with extension to left angle of mouth, wide local excision of primary tumour with supraomohyoid neck dissection with pectoralis major myocutaneous flap rotation

Fig. 3.

Fig. 3

Open in a new tab

Ulceroproliferative growth over left buccal mucosa with extension to left angle of mouth, wide local excision of primary tumour with supraomohyoid neck dissection with pectoralis major myocutaneous flap rotation

The patients were categorized mainly into two groups- patients with resectable tumours (group-1) and patients with unresectable tumours (group-2). Group-1 is further divided into group-1a and group-1b. group-1a is further divided into group-1aA and group-1aB. Group-2 is further divided into group-2a and group-2b.

  • Group- 1a: patients with resectable tumours, subjected to induction chemotherapy and surgical intervention

  • Group- 1aA: patients with resectable tumours, showed response to induction chemotherapy and underwent surgical intervention

  • Group-1aB: patients with resectable tumours, didn’t show response to induction chemotherapy and underwent surgical intervention

  • Group- 1b: patients with resectable tumours, subjected to surgical intervention without chemotherapy

  • Group- 2a: patients with unresectable tumours, subjected to induction chemotherapy and showed response then underwent surgical intervention

  • Group- 2b: patients with unresectable tumours, sent for radiotherapy.

Results

Total cases included in this study are 50. Out of which 39 (78%) patients were males and 11 (22%) patients were females. 29 (58%) patients were between 41 and 60 years of age group, followed by 17 (34%) patients were less than 40 years of age and 4 (8%) were in age group above 60 years. Mean age-45.92 years (range: 32–65 years), 45 (90%) patients had primary lesion in oral cavity while 5 (10%) patients had primary lesion in larynx (Fig. 4; Table 1).

Fig. 4.

Fig. 4

Open in a new tab

Showing distribution of cases on the basis of TNM staging before chemotherapy

Table 1.

Showing distribution of cases on the basis of sub site of occurrence of lesion

Sub site of lesion No. of patients (n = 50) Percentage
Oral cavity Tongue Ant.2/3 7 14
Post.1/3 3 6
Mid. buccal mucosa 19 38
Gingivobuccal sulcus Upper 6 12
Lower 4 8
Soft palate 1 2
Retromolar trigone 4 8
Lower lip 1 2
Larynx Supraglottic area 4 8
Glottic area 1 2
Subglottic area 0 0
Open in a new tab

TNM staging based on histopathology report with chemotherapy shows 5 (25%) patients had T2N1M0 stage and 5 (25%) patients had T1N1M0 stage, 4 (20%) patients had T4N2M0 stage, 4 (20%) patients had T4N1M0, 2 (10%) patients had T3N1M0 stage, TNM staging based on histopathology report without chemotherapy shows 10 (66.6%) patients had T2N1M0 stage, 3 (20%) patients had T3N1M0 stage, 1 (6.7%) patients had T1N1M0 stage, 1 (6.7%) patients had T4N2M0 stage (Fig. 5).

Fig. 5.

Fig. 5

Open in a new tab

Showing distribution of cases on the basis of TNM staging after chemotherapy

Among resectable tumours, 9 (60%, 25.8%) patients showed response while 6 (40%, 17.2%) patients showed no response. Among unresectable tumours, 5 (25%, 14.2%) patients showed response while 15 (75%, 42.8%) patients showed no response.

Discussion

The study was conducted on patients who underwent appropriate treatment interventions in oral and laryngeal squamous cell carcinoma to access the type of treatment given and its efficacy. According to Shukla et al. [14] study population consisted of 71 (57%) males and 53 (43%) females with mean age of the patients was 50.4 ± 12.0 years. This study suggests the age group and gender distribution was in some contrast with our study. Gnanaguru et al. [15] study population consisted of 22 (84%) males and 4 (16%) females with median age of 45 years. This suggests that obtained numericals in our study were in accordance with their study. Tandon et al. [16] conducted a study in which 31.47% had carcinoma of buccal mucosa, 21.5% patients had lesion at gingivobuccal sulcus, 19.21% had carcinoma of tongue. The available data of this study has some similarities in terms of incidence of carcinomas at various sites of oral cavity in comparison with our study. In a study conducted by Dasgupta et al. [17], they found that out of 108 patients which were selected for the study, buccal mucosa was the common site of primary lesion (36,33.33%), followed by tongue(26,24.07%), third was retromolar trigone which accounts for (16,14.81%), (13,12.04%) lesion of larynx, (1,0.93%) cases were of lip and (1,0.93%) cases were of palate. Most of the findings noted and compared in this study were found to be in similarity with our study. Yasin et al. [18] conducted a study, out of 100 patients of squamous cell carcinoma, they found that majority of the patients had moderately differentiated squamous cell carcinoma (78,76.5%), followed by well differentiated (19,18.6%) then poorly differentiated (3,2.9%). This study suggests that the values obtained were in similar comparison with our study. Dascălu et al. [19] conducted a study where they found that, out of 115 patients, 85 patients (73,91%) had stage III & IV tumors, 28 patients (22,60%) had stage II and only 2 patients (1,7.3%) had ‘in situ’ carcinoma. This study suggests that the obtained numericals were in accordance with our study.

In a study conducted by Chinn et al. [20], 10 (53%) patients showed response, while rest 9 (47%) showed no response. This study suggests that the obtained numerical were in similarity with our study. In a study conducted by Gnanaguru et al. [21] 2 (9.5%) patients showed complete response while 14 (66.7%) patients showed partial response, 4 (19%) patients had stable disease and 1 (4.8%) patient had progressive disease. This study also suggests that the procured results were in accordance with our study. Patil et al. [22] conducted a study in which they found that, out of 123 patients who received chemotherapy, resectability was achieved in 53 (43%) patients. This suggests that the obtained results were in near comparison with our study. Koch et al. [23], out of 486 patients, they found that 168 (35%) patients were found to have T2 stage of tumours followed by 133 (27%) patients had T1 stage of tumours, 102 (21%) patients had T4 staging of tumours and 83 (17%) patients had T3 staging of the tumours. This study suggests that the obtained values were in some accordance with our study. The types of neck dissection of patients who underwent surgical intervention were categorized and we found that, out of 35 patients, 28 (80%) patients underwent supraomohyoid neck dissection followed by 2 (6%) patients underwent modified radical neck dissection type II followed by 2 (6%) patients underwent jugular neck dissection and 3 (8%) patients haven’t underwent any kind of neck dissection. According to a study conducted by Rani et al. [24], out of 10 patients who underwent neck dissection, they found that 6 (60%) of the patients underwent supraomohyoid neck dissection and 4 (40%) patients underwent modified radical neck dissection. This study suggests that the results were in similar comparison with our study. Anil et al. [25] conducted a study, 174 (67%) patients underwent selective neck dissection and 60 (23%) patients under went modified radical neck dissection. This study shows the results were in accordance with our study.

Conclusion

The patients with well differentiated squamous cell carcinoma though didn’t respond well to the administered chemotherapy, but depending on the stage of tumour at the time of presentation, one can chose for the surgical intervention with or without radiotherapy if possible. The patients with moderately differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma showed satisfactory response to the chemotherapy and even the results of surgical intervention showed tumour free margins of the specimens and nodes negative for malignancy on histopathological examination than in patients who didn’t respond well with chemotherapy.

In this study, we recommend that the borderline category of patients who are initially in an unresectable tumour stage can undergo induction chemotherapy to downstage and shrink the tumour to a resectable stage following which the appropriate surgical intervention should be done with a close monitoring and sustained follow up to prevent recurrence.

Funding

The authors have no relevant financial or non-financial interests to disclose.

Declarations

Competing interests

The authors have no competing interests to declare that are relevant to the content of this article. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. The authors have no financial or proprietary interests in any material discussed in this article. Authors are responsible for correctness of the statements provided in the manuscript.

Human and Animal Rights

Research involved human participants only, after duly taking informed consent and obtaining ethical clearance from the institution.

Footnotes

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

  • 1.Joshi P, Dutta S, Chaturvedi P, Nair S. Head and neck cancers in developing countries. Rambam Maimonides Med J. 2014;5(2):e0009. doi: 10.5041/RMMJ.10143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Masud D, Gilbert P. Secure sterile head drape for head and neck surgery. J Plast Reconstr Aesthet Surg. 2009;62(01):143–144. doi: 10.1016/j.bjps.2008.06.034. [DOI] [PubMed] [Google Scholar]
  • 3.Kulkarni MK. Head and neck cancer burden in India. Int J Head Neck Surg. 2013;4:29–35. doi: 10.5005/jp-journals-10001-1132. [DOI] [Google Scholar]
  • 4.Guru K, Manoor UK, Supe SS. A comprehensive review of head and neck cancer rehabilitation: physical therapy perspectives. Indian J Palliative Care. 2012;18(2):87–97. doi: 10.4103/0973-1075.100820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Franceschi S, Talamani R, Barra S, et al. Smoking and drinking in relation to cancer of the oral cavity, pharynx, larynx and oesophagus in Northern Italy. Can Res. 1990;50:6502–6507. [PubMed] [Google Scholar]
  • 6.Blot WJ, McLaughlin JK, Winn DM, et al. Smoking and drinking in relation to oral and pharyngeal cancer. Can Res. 1988;48:3282–3287. [PubMed] [Google Scholar]
  • 7.Blot WJ. Alcohol and cancer. Can Res. 1992;52(Suppl. 7):2119s–s2123. [PubMed] [Google Scholar]
  • 8.Krishnamurthy S, Dong Z, Vodopyanov D, Imai A, Helman JI, Prince ME, Wicha MS, Nör JE. Endothelial cell-initiated signaling promotes the survival and self-renewal of cancer stem cells. Cancer Res. 2010;70(23):9969–78. doi: 10.1158/0008-5472.CAN-10-1712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Scott Brown‟s otorhinolaryngology head & neck surgery, 8th edition volume 3, Head and neck surgery, plastic surgery, chap-24, pp 393
  • 10.Gregoire V, Lefebvre JL, Licitra L, Licitra L, Felip E. EHNS-ESMO-ESTRO Guidelines Working Group Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(Suppl. 5):v184–v186. doi: 10.1093/annonc/mdq185. [DOI] [PubMed] [Google Scholar]
  • 11.Amin MBES, Greene FL et al. eds, (2017) AJCC Cancer Staging Manual. 8th ed. Springer International Publishing: American Joint Commission on Cancer; New York
  • 12.Ma J, Liu Y, Yang X, et al. Induction chemotherapy in patients with resectable head and neck squamous cell carcinoma: a meta-analysis. World J Surg Onc. 2013;11:67. doi: 10.1186/1477-7819-11-67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981;47:207–214. doi: 10.1002/1097-0142(19810101)47:1<207::AID-CNCR2820470134>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
  • 14.Shukla NK, Deo SVS, Garg PK, Manjunath NML, Bhaskar S, Sreenivas V. Operable oral tongue squamous cell cancer: 15 years experience at a tertiary care center in North India. Indian J Surg Oncol. 2018;9(1):15–23. doi: 10.1007/s13193-017-0658-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Gnanaguru V, Dhanushkodi M, Radhakrishnan V, Kalaiarasi JP, Rajan AK, Selvarajan G, Kesana S, Kothandaraman S, Sekhar S, Vaidhyalingam V, Krishnamurthi A, Nagarajan A, Ramanaiah K, Kumar H, Kumar A, Madhavan R, John A, Ranganathan R, Ganesan TS, Sagar TG. Induction chemotherapy in locally advanced head-and-neck squamous cell carcinoma: real-world outcome. Oncol J India. 2020;4:105–9. doi: 10.4103/oji.oji_21_20. [DOI] [Google Scholar]
  • 16.Tandon P, Dadhich A, Saluja H, Bawane S, Sachdeva S. The prevalence of squamous cell carcinoma in different sites of oral cavity at our Rural Health Care Centre in Loni, Maharashtra - a retrospective 10-year study. Contemp Oncol (Pozn) 2017;21(2):178–183. doi: 10.5114/wo.2017.68628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Dasgupta S, Chakrabarti S, Deb AR. Clinicopathological profile of head and neck squamous cell carcinoma. Indian J Med Paediatr Oncol. 2019;40:369–373. doi: 10.4103/ijmpo.ijmpo_180_17. [DOI] [Google Scholar]
  • 18.Yasin MM, Abbas Z, Hafeez A. Correlation of histopathological patterns of OSCC patients with tumor site and habits. BMC Oral Health. 2022;22:305. doi: 10.1186/s12903-022-02336-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Dascălu IT, et al. Histopathological aspects in oral squamous cell carcinoma. J Dental Sci. 2018;3(2):000173. [Google Scholar]
  • 20.Chinn SB, Spector ME, Bellile EL, et al. Efficacy of induction selection chemotherapy vs primary surgery for patients with advanced oral cavity carcinoma. JAMA Otolaryngol Head Neck Surg. 2014;140(2):134–142. doi: 10.1001/jamaoto.2013.5892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Gnanaguru V, Dhanushkodi M, Radhakrishnan V, Kalaiarasi JP, Rajan AK, Selvarajan G, Kesana S, Kothandaraman S, Sekhar S, Vaidhyalingam V, Krishnamurthi A, Nagarajan A, Ramanaiah K, Kumar H, Kumar A, Madhavan R, John A, Ranganathan R, Ganesan TS, Sagar TG. Induction chemotherapy in locally advanced head-and-neck squamous cell carcinoma: real-world outcome. Oncol J India. 2020;4:105–9. doi: 10.4103/oji.oji_21_20. [DOI] [Google Scholar]
  • 22.Patil VM, Noronha V, Joshi A, Muddu VK, Gulia S, Bhosale B, Arya S, Juvekar S, Chatturvedi P, Chaukar DA, Pai P, D'cruz A, Prabhash K. Induction chemotherapy in technically unresectable locally advanced oral cavity cancers: does it make a difference? Indian J Cancer. 2013;50(1):1–8. doi: 10.4103/0019-509X.112263. [DOI] [PubMed] [Google Scholar]
  • 23.Koch WM, Ridge JA, Forastiere A, Manola J. Comparison of clinical and pathological staging in head and neck squamous cell carcinoma: results from Intergroup Study ECOG 4393/RTOG 9614. Arch Otolaryngol Head Neck Surg. 2009;135(9):851–858. doi: 10.1001/archoto.2009.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Rani P, Bhardwaj Y, Dass PK, Gupta M, Malhotra D, Ghezta NK. Neck dissection for oral squamous cell carcinoma: our experience and a review of the literature. J Korean Assoc Oral Maxillofac Surg. 2015;41(6):299–305. doi: 10.5125/jkaoms.2015.41.6.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.D’Cruz Anil K, Richa V, Neeti K, Mitali D, Sudeep G, Rohini H, Jai PA, et al. Elective versus therapeutic neck dissection in node-negative oral cancer. New England J Med. 2010;373(6):521–29. doi: 10.1056/NEJMoa1506007. [DOI] [PubMed] [Google Scholar]

Articles from Indian Journal of Otolaryngology and Head & Neck Surgery are provided here courtesy of Springer

RESOURCES