Journal of Head & Neck Physicians and Surgeons

EDITORIAL
Year
: 2021  |  Volume : 9  |  Issue : 1  |  Page : 1--3

Progress in head-and-neck cancer: Promise versus reality


Tejpal Gupta1, Jai Prakash Agarwal2,  
1 Department of Radiation Oncology, ACTREC, Tata Memorial Centre, HBNI, Kharghar, Navi Mumbai, India
2 Department of Radiation Oncology, Tata Memorial Centre, HBNI, Parel, Mumbai, Maharashtra, India

Correspondence Address:
Jai Prakash Agarwal
Professor, and Head, Department of Radiation Oncology, Tata Memorial Centre, HBNI, Parel, Mumbai
India




How to cite this article:
Gupta T, Agarwal JP. Progress in head-and-neck cancer: Promise versus reality.J Head Neck Physicians Surg 2021;9:1-3


How to cite this URL:
Gupta T, Agarwal JP. Progress in head-and-neck cancer: Promise versus reality. J Head Neck Physicians Surg [serial online] 2021 [cited 2021 Dec 2 ];9:1-3
Available from: https://www.jhnps.org/text.asp?2021/9/1/1/319743


Full Text



The past two decades have witnessed major scientific advances, both technological and biological, that have bolstered our diagnostic and therapeutic armamentarium against head-and-neck cancer[1] with the promise to significantly improve disease-related outcomes as well as health-related quality-of-life (QOL). However, it still needs to be ascertained both at a global level as well as national/local level whether such promise has been realized in clinical practice by the head-and-neck oncology community.[2]

Head-and-neck cancer is not a single disease but comprises a heterogeneous group of cancers associated with similar risk factors that arise in the upper aerodigestive tract, but have distinct clinicodemographic profile, symptom burden, treatment, and outcomes. As per GLOBOCAN estimates,[3] a total of 6,50,000 new cases of head-and-neck cancer were diagnosed in the year 2016, making it the 6th most common cause of cancer worldwide. Conventionally, alcohol and tobacco-induced carcinogenesis were implicated in the etiopathogenesis of vast majority of head-and-neck cancers.[3],[4] However, the landscape of head-and-neck cancer has changed substantially over time with human papillomavirus (HPV)-associated oropharyngeal squamous cell cancer emerging as a distinct new disease entity[5],[6] with ever-increasing incidence, particularly in the developed world in parallel with gradual but consistent decline in tobacco-related cancer. This epidemiological shift is somehow not reflected in many developing countries including India, which continues to have much lower yet highly variable prevalence of HPV-associated head-and-neck cancer[7],[8] with chewing-tobacco-related cancer being the predominant form. Widespread use of chewable tobacco transforms the epithelial lining of the oral mucosa (alveolo-buccal complex and tongue) making the oral cavity the most common site of primary within the head–and-neck region in India thereby providing unique challenges as well as opportunities.[9]

Surgery had been one of the cornerstones of curative-intent therapy for head-and-neck cancer that has been practiced for over 100 years.[1] There has been increasing attention to the preservation of form and function during surgical planning. Advances in microsurgery and plastic surgery with free flaps and composite tissue transfers provide the ability to our current generation of surgeons to reconstruct virtually any defect in the head-and-neck region. However, despite achieving acceptable cancer control and cure, poor functional and cosmetic outcomes attendant to such radical surgery have spurred and driven more conservative and function-sparing surgical approaches in recent times to preserve and maintain QOL. The classic example of such transformation from radical approach to conservative surgery is the transition from radical neck dissection to modified neck dissection/selective neck dissection and even sentinel lymph node biopsy in the management of the neck. The development of minmally invasive techniques has led transoral laser microsurgery, endoscopic/endonasal skull-base surgery, and transoral robotic surgery being established in well-defined indications leading to better functional and cosmetic outcomes without compromising cancer control.

In parallel, high-quality evidence[10],[11] from prospective randomized controlled trials has firmly established combined modality treatment (radiotherapy and chemotherapy) as the current standard of care in the non-surgical management of locally advanced head-and-neck cancers. Definitive radiotherapy with concurrent cisplatin-based chemotherapy[10],[11] or induction chemotherapy followed by definitive concurrent (chemo) radiotherapy[10],[12] is the backbone of contemporary organ-preservation protocols designed to provide cure while maintaining organ form and function. Conventionally, head-and-neck irradiation comprised of conventional techniques either as parallel opposed portals with or without matched low anterior neck field or wedge-pair technique based on two-dimensional fluoroscopic imaging without major emphasis on shielding normal tissues resulting in considerable acute and late morbidity.[2],[13] Acute toxicity of irradiation can sometimes lead to interruption and even premature discontinuation of therapy with potential adverse impact on outcomes, while persistent salivary gland hypofunction can lead dryness of mouth, oral discomfort, and difficulty in speech and swallowing with negative impact upon health-related QOL. Over the years, technological advances in treatment planning and delivery have resulted in progressive conformation of radiation dose to the target tissues while sparing adjacent organs-at-risk. Intensity-modulated radiation therapy-an advanced form of high-precision conformal technique that uses nonuniform beam intensities through computer-controlled optimization to achieve the desired dose distribution is currently the most preferred technique in the curative-intent radiotherapeutic management of head-and-neck cancer.[13] The advent of in-room imaging on modern linear accelerators allows daily volumetric verification and online correction of set-up errors ushering the era of image-guided radiation therapy that could potentially allow smaller margins leading to reduction in the volume of irradiation and resultant normal tissue toxicity.[2] Adaptive re-planning and the use of functional imaging for guiding selective dose-escalation might further improve outcomes during high-precision radiotherapy of head-and-neck cancers.[2],[14] Proton beam therapy with its superior depth-dose characteristics can further improve the therapeutic index of irradiation,[15] but is neither widely available nor affordable by majority of patients even in the developed world.

The development of newer systemic therapies including chemotherapy, targeted therapy, and immunotherapy continues to advance the field of head-and-neck oncology beyond methotrexate, 5-fluorouracil, and platinum compounds. The use of taxanes (paclitaxel and docetaxel) is now firmly established in the neoadjuvant/induction chemotherapy setting[12] and is being tested with irradiation in the concurrent setting[16] for locoregionally advanced head-and-neck cancer. Epidermal growth factor receptor (EGFR) plays a crucial role in cellular growth and proliferation and is markedly overexpressed in tumor cells compared to normal cells making it an attractive therapeutic target. The addition of cetuximab an EGFR-targeting monoclonal antibody to radiation was demonstrated to result in significant improvement in outcomes[17] compared to radiation alone in patients considered ineligible for high-dose cisplatin-based concurrent chemoradiotherapy. The next generation of EGFR and other tyrosine kinase inhibitors are currently being tested in several solid cancers including head-and-neck cancers. Recently, immune checkpoint inhibitors targeting the programmed death (PD)-1 (nivolumab, pembrolizumab), PD-ligand 1 (avelumab), and cytotoxic T-lymphocyte associated (CTLA)-4 (ipilimumab) have shown promise both in the palliative setting for recurrent/metastatic head and neck cancers as well as curative-intent setting for newly-diagnosed patients.[18] Despite the use of modern conformal techniques, chemo-radiotherapy has substantial treatment-related morbidity, prompting de-escalation and de-intensification of treatment in patients with low-risk and/or favorable-biology disease such as HPV-associated oropharyngeal cancer with expected long-term survival. An unplanned post hoc subgroup analysis of the Bonner trial[17] confirmed the survival benefit of adding cetuximab in HPV-positive oropharyngeal cancer, suggesting that cetuximab-based bioradiotherapy could be a potential strategy for treatment de-intensification in this favorable biology disease. However, the substitution of cisplatin with cetuximab was associated with clearly inferior locoregional control and overall survival[19],[20] rendering such treatment untenable even for such low-risk disease. Advances in allied disciplines such as imaging (radiology and nuclear medicine), pathology (histopathology and molecular diagnostics), dental sciences (oro-dental care and prosthetics), rehabilitative services (speech, swallowing, physiotherapy, and occupational therapy), supportive care (including medical care, nursing care, social services, and patient support groups) and access to information (online and internet-based resources) have kept pace with advances in therapy leading to an integrated and multi-disciplinary team approach for optimizing outcomes in head-and-neck cancer.

It is axiomatic to state that 'prevention is better than cure'. A substantial proportion of head-and-neck cancers can be prevented by simple lifestyle changes[21] such as cessation of alcohol and tobacco, avoidance of prolonged sun exposure, and nonindulgence in sexually promiscuous behavior. Progress in medicine is driven by coordinated global research in epidemiology, etiopathogenesis, biology, diagnostics, therapeutics, and survivorship in any discipline including head-and-neck oncology. Studies conducted through the International Head and Neck Cancer Epidemiology Consortium provide better understanding of the causes and mechanistic aspects of head-and-neck cancer[22] that can translate into cancer prevention programs as well as identify relevant therapeutic targets for treatment. With the increasing incidence of head-and-neck cancer, particularly in developing countries, capacity building is imperative to create a competent and trained workforce to tackle the growing menace of head-and-neck cancer. The International Federation of Head and Neck Oncologic Societies (IFHNOS)-a global organization established through co-operation of various national and regional professional associations-provides a common platform for specialists in the field of head-and-neck cancer to interact in professional matters of common interest and coordinates a global educational fellowship program in head-and-neck oncology. The Foundation for Head and Neck Oncology-a multi-specialty national society for head-and-neck cancer in India-is a constituent member of the IFHNOS and aspires to oversee the standards of care, education, and research in head and neck oncology in the country. Finally, true progress in head-and-neck cancers can be assessed through quality performance indicators and patient satisfaction surveys designed and developed for a particular healthcare setting as proxy measures for delivery of quality of care.[23]

Disclosure

This material has never been published and is not currently under evaluation in any other peer reviewed publication.

Ethical approval

Not applicable.

Informed consent

Not Applicable.

References

1Shah JP. A century of progress in head and neck cancer. J Head Neck Phys Surg 2016;4:50-58.
2Tejpal G, Jaiprakash A, Susovan B, Ghosh-Laskar S, Murthy V, Budrukkar A. IMRT and IGRT in head and neck cancer: Have we delivered what we promised? Indian J Surg Oncol 2010;1:166-85.
3Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
4Mishra A, Meherotra R. Head and neck cancer: Global burden and regional trends in India. Asian Pac J Cancer Prev 2014;15:537-50.
5Gillison ML. Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity. Semin Oncol 2004;31:744-54.
6Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 2011;29:4294-301.
7Murthy V, Swain M, Teni T, Pawar S, Kalkar P, Patil A, et al. Human papillomavirus/p16 positive head and neck cancer in India: Prevalence, clinical impact, and influence of tobacco use. Indian J Cancer 2016;53:387-93.
8Nandi S, Mandal A, Chhebbi M. The prevalence and clinico-pathological correlation of human papillomavirus in head and neck squamous cell carcinoma in India: A systematic review article. Cancer Treat Res Commun 2021;26:100301.
9Mummudi N, Agarwal JP, Chatterjee S, Mallick I, Ghosh-Laskar S. Oral cavity cancer in the Indian subcontinent-Challenges and opportunities. Clin Oncol (R Coll Radiol) 2019;31:520-8.
10Pignon JP, Bourhis J, Domenge C, Designé L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: Three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 2000;355:949-55.
11Pignon JP, le Maître A, Maillard E, Bourhis J, MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009;92:4-14.
12Vidal L, Ben Aharon I, Limon D, Cohen E, Popovtzer A. Role of induction chemotherapy prior to chemoradiation in head and neck squamous cell cancer-systematic review and meta-analysis. Cancer J 2017;23:79-83.
13Gupta T, Kannan S, Ghosh-Laskar S, Agarwal JP. Systematic review and meta-analyses of intensity-modulated radiation therapy versus conventional two-dimensional and/or or three-dimensional radiotherapy in curative-intent management of head and neck squamous cell carcinoma. PLoS One 2018;13:e0200137.
14Paterson C, Hargreaves S, Rumley CN. Functional imaging to predict treatment response in head and neck cancer: How close are we to biologically adaptive radiotherapy? Clin Oncol (R Coll Radiol) 2020;32:861-73.
15Blanchard P, Gunn GB, Lin A, Foote RL, Lee NY, Frank SJ. Proton therapy for head and neck cancers. Semin Radiat Oncol 2018;28:53-63.
16Behera M, Owonikoko TK, Kim S, Chen Z, Higgins K, Ramalingam SS, et al. Concurrent therapy with taxane versus non-taxane containing regimens in locally advanced squamous cell carcinomas of the head and neck (SCCHN): A systematic review. Oral Oncol 2014;50:888-94.
17Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006;354:567-78.
18Galvis MM, Borges GA, Oliveira TB, Toledo IP, Castilho RM, Guerra ENS, et al. Immunotherapy improves efficacy and safety of patients with HPV positive and negative head and neck cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol 2020;150:102966.
19Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): A randomised, multicentre, non-inferiority trial. Lancet 2019;393:40-50.
20Mehanna H, Robinson M, Hartley A, Kong A, Foran B, Fulton-Lieuw T, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): An open-label randomised controlled phase 3 trial. Lancet 2019;393:51-60.
21Irani S. New insights into oral cancer-risk factors and prevention: A review of literature. Int J Prev Med 2020;11:202.
22Bravi F, Lee YA, Hashibe M, Boffetta P, Conway DI, Ferraroni M, et al. Lessons learned from the INHANCE consortium: An overview of recent results on head and neck cancer. Oral Dis 2021;27:73-93.
23Verleye L, De Gendt C, Leroy R, Stordeur S, Schillemans V, Savoye I, et al. Patterns and quality of care for head and neck cancer in Belgium: A population-based study. Eur J Cancer Care (Engl) 2021;22;e13454. DOI: 10.1111/ecc.13454.