|ORIGINAL ARTICLE - EVALUATIVE STUDY
|Year : 2021 | Volume
| Issue : 1 | Page : 27-31
Feasibility of use of the 8th edition of the American Joint Committee on Cancer staging for head and neck cancers in Indian scenario: An evaluative study
Kalpa Pandya1, Sivakumar Pradeep2, Naveen Kumar Jayakumar1, Sivakumar Vidhyadharan2, Naveen Hedne2
1 Department of Oral and Maxillofacial Surgery, Faculty of Dental Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
2 Department of Head and Neck Surgical Oncology, Apollo Proton Cancer Center, Chennai, Tamil Nadu, India
|Date of Submission||15-Apr-2020|
|Date of Decision||21-Jan-2021|
|Date of Acceptance||03-Feb-2021|
|Date of Web Publication||24-Jul-2021|
Dr. Sivakumar Pradeep
82/1, F Block, Second Street, Anna Nagar East, Chennai - 600 102, Tamil Nadu
Introduction: Inclusion of depth of invasion (DOI) and a separate classification for human papillomavirus (HPV)-associated Oropharyngeal Cancers (OPCs) are two of the many major changes in the 8th edition of the American Joint Committee on Cancer staging system. After more than 2 years of implementation, the authors found the need to evaluate if the Indian clinicians found it feasible to apply the system in their practice and if the same has influenced their decision-making. Methods: The survey was done in the form of a questionnaire which was distributed personally and via the internet to 100 clinicians. Seventy-two clinicians responded to the questionnaire. The results were analyzed and frequency distribution was computed. Results: Eighty-three percent of the clinicians experienced that palpation of the tumour was not a reliable method to determine the DOI. The common issues stated by the clinicians were difficulty in assessing DOI in certain subsites of the oral cavity (most commonly retromolar trigone–83%), inability to determine DOI in patients with trismus, and inability to correlate pathological and clinical DOI. Thirteen percent of the clinicians did not rely on radiological tools for measuring the DOI. Seventy percent of the clinicians did not perform a P16 assay for patients with oropharyngeal cancers. Fifty percent of the clinicians preferred chemoradiotherapy for early HPV positive oropharyngeal cancers. Discussion: Based on the results of the survey, the authors recommend a need for more interpretative guidelines and methods for determining the DOI. The authors also emphasize the need for determining HPV status for all oropharyngeal carcinomas.
Keywords: Classification, mouth neoplasms, neoplasm staging, oropharyngeal neoplasms, P16 protein
|How to cite this article:|
Pandya K, Pradeep S, Jayakumar NK, Vidhyadharan S, Hedne N. Feasibility of use of the 8th edition of the American Joint Committee on Cancer staging for head and neck cancers in Indian scenario: An evaluative study. Ann Maxillofac Surg 2021;11:27-31
|How to cite this URL:|
Pandya K, Pradeep S, Jayakumar NK, Vidhyadharan S, Hedne N. Feasibility of use of the 8th edition of the American Joint Committee on Cancer staging for head and neck cancers in Indian scenario: An evaluative study. Ann Maxillofac Surg [serial online] 2021 [cited 2021 Dec 5];11:27-31. Available from: https://www.amsjournal.com/text.asp?2021/11/1/27/322231
| Background|| |
The 8th edition of the American Joint Committee on Cancer (AJCC) staging system was published in 2017 and was applied for all cases diagnosed on and after January 1, 2018. The major changes in the eighth edition include:
- Inclusion of depth of invasion (DOI) of oral cavity cancers
- Upstaging of nodal staging based on extranodal extension
- Reclassification of oropharyngeal cancers based on human papillomavirus (HPV) expression
- Testing for HPV and Epstein–Barr virus (EBV) in all cases of cervical metastasis of unknown origin.
It has been recognized since the early work of Spiro et al. that the prognosis of the diseases becomes worse as the thickness of the tumour increases. It is now a well-accepted fact that DOI is more representative of tumour infiltration than the tumour thickness. Increase in DOI is known to increase the risk of nodal metastasis and recurrence., However, difficulty in measuring DOI clinically in certain subsites and interobserver variability makes this parameter challenging to assess.
In the recent times, there has been a rise in the HPV-associated oropharyngeal cancers. In the 8th edition of the tumour, node, and metastasis (TNM) staging system, AJCC recommends determination of P16 status of all oropharyngeal cancers to classify the HPV-positive cancers separately, owing to the better prognosis that HPV-positive oropharyngeal cancers offer in comparison to those which do not demonstrate HPV. It has been stated that in the Indian scenario, lack of infrastructure for immunohistochemistry (IHC) in certain facilities and low socioeconomic status make application of this system slightly difficult. Affordable cancer diagnosis and treatment are one of the challenges faced by the Indian public health system. This makes approach of patients and hence the clinicians slightly varied toward cancer diagnosis and treatment than that in the developed nations.
We conducted a nationwide survey to evaluate feasibility and the use of recent AJCC staging of the head and neck among clinicians actively involved in the treatment of head and neck cancers, the area of focus being measurement of DOI in oral cavity cancers and HPV determination in oropharyngeal cancers.
| Methods|| |
This was an evaluative cross sectional study. The study duration was 3 months. The data were collected through a questionnaire [Table 1] consisting of 7 questions, distributed personally and via the internet. A total of 100 clinicians across India were approached to participate in the study, of which 72 clinicians responded. Inclusion criteria included those clinicians actively involved in diagnosis and management of head and neck cancers. The questionnaire was validated by an internal committee from the institutions where the study was designed. The question 1 and question 2 were aimed to identify if the clinicians were able to measure the DOI with ease and if they experienced greater trouble in measuring DOI in any specific subsites of the oral cavity. Question 3 explored if the clinicians relied on imaging for assessing the DOI. Question 4 enquired if there was any change in treatment strategy due to the upstaging of oral cavity cancers on inclusion of DOI. Question 5 focused on whether clinicians determined HPV status of all oropharyngeal cancer patients they encounter. Question 7 asked the clinicians their choice of treatment for HPV-positive early oropharyngeal cancers. Since the study did not involve comparison of any variables or groups, statistical analysis was not performed. The responses were analyzed and frequency distribution was computed.
|Table 1: Eighth edition of the American Joint Committee on Cancer feasibility questionnaire|
Click here to view
| Results|| |
The question-wise results were as follows:
As a response to question 1, 78% of the respondents answered that they did not feel that palpation of the tumour was a reliable method to measure the DOI. Twenty percent of the respondents stated that it was not precise and 13% of respondents felt that it was subjective and had inter observer variability. Pain and gag reflex made examination difficult, as reported by 13% of respondents. Twenty-eight percent of the respondents found it difficult to palpate DOI in certain subsites of the oral cavity. Some of the respondents also reported that DOI was difficult to measure in tumours invading the hard tissues.
Question 2 inquired if the clinicians were able to clinically estimate the DOI in all the subsites of oral cavity and if not, which are the subsites where they encounter difficulty. Ninety-two percent of the respondents were not able to clinically estimate the DOI in certain subsites. The sites where DOI was most difficult to assess were retromolar trigone, hard palate, alveolus, and gingivobuccal sulcus.
As a response to question 3, 87% of the respondents agreed to be relying on radiological tools for measuring the DOI.
Question 5 inquired regarding their preferred modality of treatment for a tumour that is 3 cm in size and >10 mm in clinical DOI. Ninety percent of the respondents opted for multimodality treatment.
On analyzing responses to question 6, it was found that 70% of the respondents did not advise HPV determination as a routine practice. The reasons behind this were IHC not being available in their setup, test being expensive, unwillingness of the patient, and the fact that there is no conclusive evidence to alter the treatment plan in these cases.
While replying to question 7, 50% of the respondents preferred to opt for chemoradiotherapy whereas 30% opted for transoral robotic surgery [TORS] as the choice of treatment for HPV positive early oropharyngeal cancers. The rest 20% of the respondents did not respond to question 6.
| Discussion|| |
Staging forms a pivotal role in establishing the diagnosis, treatment plan, and prognosis of cancer. Accurate staging forms a basis for interdisciplinary communication and research. AJCC in collaboration with the Union for International Cancer Control has formulated a system known as TNM, which is popularly used worldwide for clinical and research purposes.
The 8th edition of the AJCC staging system was published in 2017 and was applied for all cancer cases diagnosed on and after January 1, 2018. Significant changes have been made in the head and neck staging system in the eighth edition, based on the changing nature of cancers and advanced research in the field.
DOI has been discussed extensively in the literature as an independent prognosticator of survival and recurrence in oral cavity cancers., Ebrahimi et al. in their multicenter retrospective study demonstrated a significant association between DOI and disease-specific survival. As a result, AJCC incorporated DOI in the T criteria for oral cavity cancers in 2016, which was earlier defined by only a two-dimensional measurement of tumour diameter. Inclusion of DOI leads to upstaging of certain tumours with a small diameter but increased DOI. Seventy-eight percent of the respondents of the present survey found palpation of the tumour unreliable for measuring the DOI. Reasons stated for the same were subjectivity, pain when palpating the posterior areas, gag reflex, trismus, and inability to assess DOI in the intrabony component of the tumour. Ambiguity in measurement of the clinical depth by palpation makes one dependent on the imaging for determining the DOI. 87% of the respondents used imaging as a supplementary tool to determine the DOI. MRI is as an acceptable modality for measuring the DOI. However, inflammation and peritumoural edema tends to overestimate the depth in postcontrast MRI. Vidiri et al. have established a good correlation between radiological depth measured through contrast MRI and pathological depth. However, their study consisted of a small sample size of 43 and they insisted on measurement of DOI within 1 min of injecting the contrast (early postcontrast phase) for accurate calculation of DOI., AJCC gives clearcut guidelines for the measurement of DOI histologically through a plumb line. However, it has been observed that DOI measurement in large tumours is associated with high interobserver variability and ambiguity. This may obviate the primary aim of staging. Kano et al. in their validation study for modified AJCC staging for oral cavity cancers have suggested to improvise the method of measurement of histopathological DOI in larger tumours of the tongue.
Ninety percent of the respondents preferred multimodality treatment for a tumour that is 3 cm in size and >10 mm in clinical DOI. Addition of DOI as fundamental criteria in T staging leads to restaging of certain tumours. A tumour 3 cm in size, >10 mm in depth, which was classified as T2 in the 7th edition staging system, would now be classified as T3 as per the eight edition, taking into account the depth of the tumour. A tumour that migrates to Stage III from Stage II may need to be considered for multimodality treatment which would otherwise have been subjected to a single modality treatment and observation. Probably, with this fact in mind, 90% of the respondents in our survey have opted for multimodality treatment. However, Ebrahimi et al. in their retrospective study in a cohort of 1409 patients with tumour diameter ≤4 cm concluded that there was no association between DOI and disease-specific survival in such patients. Thus, they have advised against the use of DOI as sole criteria for postsurgical radiotherapy and thus multimodality treatment in the absence of other adverse features in patients with tumour size ≤4 cm.
In the seventh edition staging system, the staging of oropharyngeal cancers represents the behavior of cancers caused due to tobacco and alcohol and does not differentiate those associated with HPVs. High risk (HR-HPV) associated Oropharyngeal Cancers (OPCs) have a different biology than their non-HPV counterparts. Subset analysis of several clinical trials has shown that HPV-positive OPCs have a better prognosis and overall survival compared to HPV-negative ones.,, This led to the introduction of separate staging system for HPV-positive OPCs in the eight edition of AJCC manual. The recent literature shows that 25% of the oropharyngeal carcinomas are associated with HR-HPV.,, A meta-analysis by Mehanna et al. has reported an incidence of HPV in OPCs as 47.7%. However, there are sparse data regarding the prevalence of HPV in nontobacco-associated OPCs in India, since the majority of the patients with Head and Neck Squamous Cell Carcinomas (HNSCCs) are tobacco users.
There are several methods available for the detection of HPV, of which detection of P16 by IHC and detection of HPV DNA by polymerase chain reaction are being more commonly done. P16 detection by IHC has been suggested by the AJCC as an acceptable tool. P16 is overexpressed in HPV-positive cases and hence is used as a surrogate marker for HPV. IHC test is less expensive and easily available than the other tools. As per the consensus recommendations provided by the Indian Cooperative Oncology Network, HPV DNA testing in addition to P16 IHC would be desirable but can be considered optional. Seventy percent of the clinicians who responded to the survey did not routinely check the HPV status of patients with oropharynx carcinoma. Majority of them claimed to be lacking the necessary infrastructure for performing the tests. Furthermore, the test deemed to add to the cost which was not acceptable to the patients, especially those from low socioeconomic class. In view of a proven favorable prognosis of HPV-positive OPC, deescalation of treatment has been suggested for these patients to decrease the toxicity and morbidity associated with the conventional treatments. The various modalities proposed for deescalation are lower dosage of radiotherapy, replacement of chemotherapy by targeted therapy, and minimally invasive therapy. However, deescalation is currently not recommended outside of a clinical trial.
In the concluding question of the survey, 30% of the respondents preferred TORS for early oropharyngeal cancers whereas 50% of them preferred a conventional chemoradiotherapy. TORS is now deemed a viable surgical option for carcinoma oropharynx due to the good oncologic, functional, and survival outcomes., HPV-positive OPC with their proven favorable prognosis could qualify for treatment with TORS. The ORATOR trial has compared radiotherapy versus TORS and neck dissection in patients with T1-T2 lesions and positive for P16. The authors have interpreted that radiotherapy had a better swallowing-related quality of life compared to the TORS group; however, the difference did not represent a clinically significant change. They suggest to inform the patients regarding both the treatment options. TORS is available only in few centers across India. Furthermore, the clinicians trained in TORS are few. This could be the reason behind clinicians still opting conventional chemoradiotherapy compared to TORS in early OPC.
| Conclusion|| |
Feasibility of applying the 8th edition of the AJCC staging for head and neck cancers has been discussed widely in the recent literature., This survey is first of its kind assessing the feasibility and ease of implementation of Eighth edition of AJCC staging in Indian scenario. The survey reflects a need for more interpretative guidelines and methods for determining the DOI. It also emphasizes the importance of determining HPV status for all oropharyngeal carcinomas.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, et al
., editors. AJCC Cancer Staging Manual. 8th
ed. New York:Springer International Publishing; 2017. Available from: https://www.springer.com/us/book/9783319406176
. [Last accessed on 2019 May 10].
Spiro RH, Huvos AG, Wong GY, Spiro JD, Gnecco CA, Strong EW. Predictive value of tumor thickness in squamous carcinoma confined to the tongue and floor of the mouth. Am J Surg 1986;152:345-50.
International Consortium for Outcome Research (ICOR) in Head and Neck Cancer, Ebrahimi A, Gil Z, Amit M, Yen TC, Liao CT, 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;140:1138-48.
Faisal M, Abu Bakar M, Sarwar A, Adeel M, Batool F, Malik KI, et al
. 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 2018;13:e0202632.
Subramaniam N, Thankappan K, Anand A, Balasubramanian D, Iyer S. Implementing American Joint Committee on Cancer 8th
edition for head-and-neck cancer in India: Context, feasibility, and practicality. Indian J Cancer 2018;55:4-8.
] [Full text]
Ellington TD, Henley SJ, Senkomago V, O'Neil ME, Wilson RJ, Singh S, et al
. Trends in incidence of cancers of the oral cavity and pharynx-United States 2007-2016. MMWR Morb Mortal Wkly Rep 2020;69:433-8.
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al
. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010;363:24-35.
Pramesh CS, Badwe RA, Borthakur BB, Chandra M, Raj EH, Kannan T, et al
. Delivery of affordable and equitable cancer care in India. Lancet Oncol 2014;15:e223-33.
Friedland PL, Bozic B, Dewar J, Kuan R, Meyer C, Phillips M. Impact of multidisciplinary team management in head and neck cancer patients. Br J Cancer 2011;104:1246-8.
Ling W, Mijiti A, Moming A. Survival pattern and prognostic factors of patients with squamous cell carcinoma of the tongue: A retrospective analysis of 210 cases. J Oral Maxillofac Surg 2013;71:775-85.
Tan WJ, Chia CS, Tan HK, Soo KC, Iyer NG. Prognostic significance of invasion depth in oral tongue squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec 2012;74:264-70.
Alsaffar HA, Goldstein DP, King EV, de Almeida JR, Brown DH, Gilbert RW, et al
. Correlation between clinical and MRI assessment of depth of invasion in oral tongue squamous cell carcinoma. Otolaryngol Head Neck Surg 2016;45:61.
Vidiri A, Panfili M, Boellis A, Cristalli G, Gangemi E, Pellini R, et al
. The role of MRI-derived depth of invasion in staging oral tongue squamous cell carcinoma: Inter-reader and radiological-pathological agreement. Acta Radiol 2020;61:344-52.
Bullock MJ. Current challenges in the staging of oral cancer. Head Neck Pathol 2019;13:440-8.
Kano S, Sakashita T, Tsushima N, Mizumachi T, Nakazono A, Suzuki T, et al
. Validation of the 8th
edition of the AJCC/UICC TNM staging system for tongue squamous cell carcinoma. Int J Clin Oncol 2018;23:844-50.
Dufour X, Beby-Defaux A, Agius G, Lacau St Guily J. HPV and head and neck cancer. Eur Ann Otorhinolaryngol Head Neck Dis 2012;129:26-31.
Ebrahimi A, Gil Z, Amit M, Yen TC, Liao CT, Chaturvedi P, et al
. Depth of invasion alone as an indication for postoperative radiotherapy in small oral squamous cell carcinomas: An International Collaborative Study. Head Neck 2019;41:1935-42.
Fakhry C, Agrawal N, Califano J, Messing B, Liu J, Saunders J, et al
. The use of ultrasound in the search for the primary site of unknown primary head and neck squamous cell cancers. Oral Oncol 2014;50:640-5.
Kane SV, Gupta M, Kakade AC, D' Cruz A. Depth of invasion is the most significant histological predictor of subclinical cervical lymph node metastasis in early squamous carcinomas of the oral cavity. Eur J Surg Oncol 2006;32:795-803.
Mehanna H, Beech T, Nicholson T, El-Hariry I, McConkey C, Paleri V, et al
. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer — Systematic review and meta-analysis of trends by time and region. Head Neck 2013;35:747-55.
Murthy V, Calcuttawala A, Chadha K, d'Cruz A, Krishnamurthy A, Mallick I, et al
. Human papillomavirus in head and neck cancer in India: Current status and consensus recommendations. South Asian J Cancer 2017;6:93-8.
] [Full text]
Wirth LJ, Burtness B, Nathan CO, Grégoire V, Richmon J. Point/Counterpoint: Do we de-escalate treatment of hpv-associated oropharynx cancer now? and how? Am Soc Clin Oncol Educ Book 2019;39:364-72.
Weinstein GS, O'Malley BW Jr., Magnuson JS, Carroll WR, Olsen KD, Daio L, et al
. Transoral robotic surgery: A multicenter study to assess feasibility, safety, and surgical margins. Laryngoscope 2012;122:1701-7.
Moore EJ, Olsen SM, Laborde RR, García JJ, Walsh FJ, Price DL, et al
. Long-term functional and oncologic results of transoral robotic surgery for oropharyngeal squamous cell carcinoma. Mayo Clin Proc 2012;87:219-25.
Nichols AC, Theurer J, Prisman E, Read N, Berthelet E, Tran E, et al
. Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): An open-label, phase 2, randomised trial. Lancet Oncol 2019;20:1349-59.