Head & Neck Institute Outcomes
Head and Neck Surgery and Oncology
Recent and Emerging Therapies for Cutaneous Squamous Cell Carcinomas of the Head and Neck
Cutaneous squamous cell carcinoma (cSCC) is the second most common form of cancer after basal cell carcinoma (BCC). In fair-skinned individuals, the single most important risk factor is cumulative sun exposure. Other known risk factors are immune suppression, ionizing radiation, predisposing genetic disorders such as xeroderma pigmentosum, and chronic inflammation from scars, burns, or chronic ulcers. When these cancers are located on the trunk or extremities, they are often diagnosed at an early stage and safely managed with wide-local excision. However, cSCCs are commonly located on the head and neck and require unique therapeutic approaches, not only to optimize oncologic outcomes in high-risk subsets but also to improve cosmesis.
There are several risk stratification schemes in cSCC. Two of the most popular, the 8th edition of the American Joint Committee on Cancer (AJCC) and the Brigham and Woman’s Hospital (BWH) staging systems, provide different algorithms for risk-stratifying cSCC by primary tumor factors. A retrospective study of 459 patients with 680 cases of cSCC showed that the BWH staging system had higher specificity and positive predictive value for identifying tumors at risk for poor outcomes compared with the 8th edition AJCC staging system. Breuninger et al. proposed another staging system, classifying tumors as clinically high-risk when greater than 2 cm in gross diameter and pathologically high-risk when greater than 6 mm in histological thickness.
Comparison of Risk Stratification Schemes for Cutaneous Squamous Cell Carcinoma Between the 8th Edition AJCC Staging System and Brigham and Woman's Hospital Staging System
| Tumor Stage | 8th Edition AJCC System (Head and Neck Only) | Brigham and Woman's Hospital Staging Systemᵃ |
|---|---|---|
| T1 | Tumor diameter < 2 cm in greatest dimension | No high-risk factors |
| T2 | Tumor ≥ 2 cm, but < 4 cm in greatest dimension | T2a: 1 high-risk factor T2b: 2-3 high-risk factors |
| T3 | Tumor with gross cortical bone/marrow invasion | ≥ 4 high-risk factors or bone invasion |
| T4 | Tumor with skull base invasion and/or skull base foramen involvement | N/A |
ᵃHigh-risk factors are tumor diameter ≥ 2 cm, invasion beyond subcutaneous fat, poor differentiation, and perineural invasion > 0.1 mm
Cutaneous squamous cell carcinoma of the head and neck is often managed with Mohs micrographic surgery for cosmetic concerns as well as improved outcomes in high-risk subsets. High-risk subsets of tumors with adverse pathologic features and higher recurrence risks are also managed with adjuvant radiation therapy. For patients with advanced, unresectable cutaneous squamous cell carcinoma not amenable to surgery or definitive radiation therapy, cemiplimab is now the standard of care as first-line therapy with encouraging response rates that can be durable. Immunotherapeutic agents are now being tested in clinical trials in the neoadjuvant and adjuvant settings. Second generation trials in the locally advanced and metastatic population include novel immunotherapy agents, combinations of agents, and intratumoral agents. Most importantly, multidisciplinary care is increasingly critical in helping achieve optimal outcomes for these patients.
