Dear Colleagues,

Happy New Year from the American Head and Neck Society (AHNS)! It continues to be tremendously challenging times navigating the Global Pandemic and its significant pressures on our professional and personal lives. Despite these challenges, our AHNS has demonstrated strength and resilience. I would like to thank my fellow leaders and members of the society who have continued to guide this great organization and further its mission to advance education, research, quality, and equity of care for head and neck oncology patients.

Throughout the ongoing pandemic, our society maintained a high level of educational offerings through virtual education for our members, for our colleagues nationally and internationally, and for our fellows. Thank you to our sections and services who dedicated their time and expertise on webinars and virtual tumor boards. These efforts and programs were critical to advancing knowledge within our field, which in turn enables us to provide the highest quality of patient care. I look forward to these learning opportunities in 2022.

As you know, we established a new Diversity, Equity, and Inclusion (DEI) Division over this past year. Congratulations to Dr. Amy Chen, who is serving as the Interim Chair, and Dr. Melonie Nance, who is the Interim Vice-Chair. In addition, Dr. Rene Leemans is serving as the new Interim International Representative to the Executive Committee and we are grateful for all of their wisdom and guidance within our leadership team.

The leadership continues to work hard on making sure the society is relevant and meets the needs of its members. The Executive Committee will be convening at the conclusion of the Multi-Disciplinary Meeting in Phoenix this February to examine key areas of desired evolution and strategic growth. I look forward to sharing what we develop and conclude after this important strategic planning leadership meeting.

In addition to working internally on strengthening the AHNS, we have continued to expand our reputation publicly through our partnership with Stand Up to Cancer. AHNS, along with the Fanconi Anemia Research Fund, the Farrah Fawcett Foundation and the Head and Neck Cancer Alliance are working with Stand Up to Cancer to help fund a research team to concentrate on new approaches to address head and neck squamous cell carcinoma, with an emphasis on cancers related to the human papillomavirus (HPV) and Fanconi anemia. Thank you to Past President Dr. Cherie-Ann Nathan on beginning this important initiative.

We are pushing forward on having our first in-person scientific meeting since the Global Pandemic began. Please save the dates for this year’s Annual Meeting during COSM, which will occur April 27-28, 2022 in Dallas, Texas. Drs. Jim Rocco and Jeff Liu are finalizing an engaging conference and I am excited to welcome all of you for two days of enlightening education, camaraderie, and the ability to connect with each other, which has been well overdue.

Thank you all for your commitment to the AHNS. It is a real privilege and honor to serve as your President. If you have any suggestions or comments for our society, please do not hesitate to reach out to me through our AHNS headquarters office ([email protected]). My very best wishes for a safe, healthy, and happy 2022!

Bert W. O’Malley, Jr, MD
President, AHNS

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Co-authored by Akshay V. Patel, DO MA & Roshansa Singh, MD

We have seen the rise of cutaneous squamous cell carcinoma (cSCC) and it is now situated as the second most common skin cancer world-wide¹. In conjunction with basal cell carcinoma (BCC), these cancers are classified as keratinocyte carcinoma, or colloquially as nonmelanoma skin cancer. While previously seen at a lower frequency as compared to BCC, the aging population and increased cumulative ultraviolet radiation exposure has led to a rise in numbers of patients diagnosed with cSCC². A majority of patients with cSCC have favorable outcomes, with low local recurrence (3-5.2%), nodal metastasis (1.5-4%), and disease specific death (1.5-2.8%) rates^2,3,4. Surgical excision of these lesions with negative margins portends a favorable prognosis. Patients with locally advanced or recurrent disease are high risk and in the setting of metastasis, prognosis is poor^4,5,6. The ability to prognosticate outcomes and thereby model treatments in these patients is an invaluable tool in our armamentarium. Having the capability to provide early estimates of prognosis affords physicians the opportunity to describe varied treatment options with expected outcomes and can alter the approach to treatment.

The key features of an ideal staging system incorporate distinctiveness, homogeneity, and monotonicity². Distinctiveness refers to the difference in disease-related outcomes based on stage. Homogeneity, on the other hand, implies that patients within the same stage have similar outcomes. Monotonicity represents worsening outcomes with increasing stage. The increasing incidence of cSCC has fostered interest in the development of an applicable, accurate staging system that can be implemented in these patients with reproducible outcomes. The systems reviewed include the American Joint Committee on Cancer (AJCC) seventh edition, AJCC eight edition, and the Brigham and Woman’s Hospital (BWH) system.

Staging Systems

Developments in our understanding of the mechanisms at play with cSCC has allowed for steady appreciation of risk factors that contribute to the progression of this disease. This has stimulated an ever-evolving slew of staging systems, with each iteration undertaking the goal to address and incorporate the key points lacking from the previous proposal. Immunosuppression surfaced early as a significant risk factor for the development of cSCC, with patients who underwent solid organ transplantation experiencing 65-250 times the risk of developing carcinoma as compared to the general population and a higher risk for metastasis^4,7.

The 7^th edition of the AJCC staging system was published in 2010, taking into account tumor diameter and high-risk factors shown to predict adverse outcomes (tumor thickness, Clark level, differentiation, perineural invasion, location) to establish a T grade⁸. Critics of this staging system cite low specificity and variable complexity as reasons for inapplicability in a clinical setting^2,6. Next on the stage was the Brigham and Women’s Hospital system, which assigned T grade based on the number of high-risk factors (tumor diameter, invasion beyond subcutaneous fat, differentiation, quantified perineural invasion). The relative ease of applicability of this staging system has often rendered it the frontrunner in the field. Studies that compared AJCC 7^th edition to BWH attribute improved distinctiveness, homogeneity, and monotonicity in the latter^3,9. BWH includes invasion beyond subcutaneous fat and perineural invasion of large-caliber nerves (>0.1 mm) as two of its risk factors, both of which have been thought to be too exhaustive for the general clinic setting⁶. The AJCC published the eighth edition in 2016, which went into effect on 2018. With regards to cSCC, a head and neck subset was designed and high-risk factors now included deep invasion, bony erosion, and perineural invasion. This system proved to have better homogeneity and monotonicity as compared to AJCC 7, however, distinctiveness continued to lag behind, proving to be a minor setback to this system^2,3,10.

Nodal Disease

A desired goal of these staging systems is the ability to predict patients at risk for nodal metastasis and provide a stratified paradigm in which to guide treatment. The overall risk of metastasis in this disease cohort is quoted at 4%^4,10,11. There is a significantly increased rate of mortality in those with nodal metastasis, with 5-year survival rates reported at 27% as compared to 98% in those without nodal metastasis^2,9. Initial studies of cSCC staging systems and their relation to nodal disease demonstrated high risks of nodal metastasis with increasing T stage, primarily with the BWH system¹¹. Most recently, Upton et al. reviewed patients with cSCC at their institution from 2006-2017 and evaluated the ability of the AJCC 7, AJCC 8, and BWH systems to predict nodal spread¹². Keeping their limited sample size in mind, BWH was demonstrably most reliable with increasing T stage corresponding to higher risk of nodal disease.

Their results were compared to the current literature in a letter to the editor by Barriera‐Silvestrini and Knackstedt, who quoted significantly lower rates of nodal spread in each T stage when incorporating studies with larger sample sizes¹³. Upton et al. depicted that many of the T2 staged tumors in AJCC 7 were upstaged to T3 when utilizing AJCC 8, with a corresponding increase in rate of nodal disease. Similarly, a change was seen between BWH stages T2a and T2b, with T2b tumors representing higher risk of nodal metastases. Their team suggests use of these thresholds to drive discussion regarding nodal management, i.e. those with AJCC 8 T3 or BWH T2b disease to consider concurrent elective neck dissection. Interestingly, Barriera‐Silvestrini and Knackstedt offer a decision point as opposed to the proposition of neck dissection in these patients. They present 3 options: further radiological evaluation, sentinel lymph node biopsy, and primary tumor risk assessment.

These studies reiterate that staging systems should not be utilized in isolation. In its entirety, evaluation of cSCC presents a challenge due to its rarity, further exacerbated by the primarily favorable outcomes in this disease process. With increasing sample sizes from a multitude of studies, the ability to test the robustness of these staging systems continues to steadily improve. Discussions with patients presenting with higher stages, regardless of system, may include consideration of management of neck disease. In addition, given patient risk factors and subsequent to histological analysis, further evaluation with radiological evaluation and genetic classification remains a viable next step. CT continues to be the most commonly used modality for detecting nodal disease, especially in the face of high costs associated with PET/CT^{2, 14}.

The inherent pathogenesis of cSCC development involves a high burden of mutations secondary to ultraviolet radiation, driven primarily by inactivation of tumor suppressor genes, and at higher rates than other tumors^7,15. Critically, the role of programmed cell death ligand (PD-L1) expression was evaluated, prompting the approval of cemiplimab in 2018, currently awaiting phase II trial results^2,16. The availability of immunotherapy and preference over chemoradiation therapy, especially with regards to treatment sequelae, posits that genetic contribution should be deliberated in the treatment planning.

Conclusion

A desire for a reliable, predictive staging system for cutaneous squamous cell carcinoma has garnered much research over the past decade. Successive recapitulations of the staging systems, with both patient and pathological factors coming to the foreground seem to place the BWH and AJCC 8^th edition as the preferred paradigms. The sensitivity and specificity of these staging systems, related not only to survival but also propensity for nodal disease, continues to evolve and may ultimately improve prognostication abilities. The importance of incorporating genetic factors in the setting of a tumor that is highly susceptible to mutation secondary to its etiology should not be undervalued. At the current point, these systems can prove to be effective with regards to patient discussions of management and promote discourse between physician and patient with regards to available options.

At our institution, we prefer to use the BWH staging system, using it as a guide during our tumor board discussions and patient care. Given the relative abundance of Mohs surgeons in our area, we commonly meet patients with large tumors favoring elective nodal dissection to facilitate complex reconstruction or patients with delayed metastatic disease to the parotid gland and neck. In patients who present with delayed metastatic disease, we review the initial pathology from prior resections and apply the BWH staging system, commonly finding that many of these patients had advanced local disease and high risk factors at their initial presentation, predictive of their risks for nodal disease.

Which staging system do you prefer and why?

References:

• Rogers HW, Weinstock MA, Feldman SR, et al. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US population, 2012. JAMA Dermatol 2015;151(10):1081–6.
• Bander TS, Nehal KS, Lee EH. Cutaneous squamous cell carcinoma: updates in staging and management. Dermatologic clinics. 2019 Jul 1;37(3):241-51.
• Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. Journal of the American Academy of Dermatology. 2013 Jun 1;68(6):957-66.
• Brantsch KD, Meisner C, Schönfisch B, Trilling B, Wehner-Caroli J, Röcken M, Breuninger H. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. The lancet oncology. 2008 Aug 1;9(8):713-20.
• Mourouzis C, Boynton A, Grant J, Umar T, Wilson A, Macpheson D, Pratt C. Cutaneous head and neck SCCs and risk of nodal metastasis–UK experience. Journal of Cranio-Maxillofacial Surgery. 2009 Dec 1;37(8):443-7.
• Roscher I, Falk RS, Vos L, Clausen OP, Helsing P, Gjersvik P, Robsahm TE. Validating 4 staging systems for cutaneous squamous cell carcinoma using population-based data: a nested case-control study. JAMA dermatology. 2018 Apr 1;154(4):428-34.
• Waldman A, Schmults C. Cutaneous squamous cell carcinoma. Hematology/Oncology Clinics. 2019 Feb 1;33(1):1-2.
• Martorell-Calatayud A, Jimenez OS, Mojarrieta JC, Barona CG. Cutaneous squamous cell carcinoma: defining the high-risk variant. Actas Dermo-Sifiliográficas (English Edition). 2013 Jun 1;104(5):367-79.
• Haisma MS, Plaat BE, Bijl HP, Roodenburg JL, Diercks GF, Romeijn TR, Terra JB. Multivariate analysis of potential risk factors for lymph node metastasis in patients with cutaneous squamous cell carcinoma of the head and neck. Journal of the American Academy of Dermatology. 2016 Oct 1;75(4):722-30.
• Alam M, Armstrong A, Baum C, Bordeaux JS, Brown M, Busam KJ, Eisen DB, Iyengar V, Lober C, Margolis DJ, Messina J. Guidelines of care for the management of cutaneous squamous cell carcinoma. Journal of the American Academy of Dermatology. 2018 Mar 1;78(3):560-78.
• Fox M, Brown M, Golda N, Goldberg D, Miller C, Pugliano-Mauro M, Schmults C, Shin T, Stasko T, Xu YG, Nehal K. Nodal staging of high-risk cutaneous squamous cell carcinoma. Journal of the American Academy of Dermatology. 2019 Aug 1;81(2):548-57.
• Upton M, Kita A, Scapa J, St. John M. Prognostic Value of Tumor Staging: Predicting Nodal Metastases in Cutaneous Squamous Cell Carcinoma. The Laryngoscope. 2021 Jan;131(1):E170-5.
• Barriera‐Silvestrini P, Knackstedt T. In Reference to Prognostic Value of Tumor Staging: Predicting Nodal Metastases in Cutaneous Squamous Cell Carcinoma. The Laryngoscope. 2021 Feb;131(2):E443-.
• Liao LJ, Lo WC, Hsu WL, Wang CT, Lai MS. Detection of cervical lymph node metastasis in head and neck cancer patients with clinically N0 neck—a meta-analysis comparing different imaging modalities. BMC cancer. 2012 Dec;12(1):1-7.
• Abraham I, Curiel-Lewandrowski C. Staging systems to predict metastatic cutaneous squamous cell carcinoma: unsatisfactory for clinical use, but some less so?. JAMA dermatology. 2018 Dec 1;154(12):1391-2.
• Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, Chung CH, Hernandez-Aya L, Lim AM, Chang AL, Rabinowits G. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. New England Journal of Medicine. 2018 Jul 26;379(4):341-51.

Roshansa Singh, MD obtained her Bachelor of Arts from Cornell University and pursued medicine at Rutgers New Jersey Medical School. She is currently in her Otolaryngology – Head and Neck Surgery residency at the University of Connecticut.

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Akshay Patel, DO MA

Dr. Akshay Patel is the co-Director of the Hartford Hospital Head and Neck Oncology Program. He is a co-founder of the Connecticut Institute for Head and Neck Surgery, a subsidiary of Connecticut Ear, Nose and Throat Associates. Dr. Patel also serves as a clinical assistant professor with the Department of Otolaryngology and Head and Neck Surgery at the University of Connecticut School of Medicine. He completed residency training in Otolaryngology/Head and Neck Surgery and Facial Plastics Surgery at NY-COM/Barnabas Medical Center and Head and Neck Surgical Oncology and Microvascular Reconstructive Surgery Fellowship at University Hospitals – Case Western School of Medicine in Cleveland, OH.

Latest posts by Akshay Patel, DO MA (see all)

• The Evolution of Staging Cutaneous Squamous Cell Carcinoma: The Role of T Grade - December 16, 2021