DANGER: what clinicians need to know about aggressive head and neck cutaneous squamous cell carcinoma

Richard Tjahjono, Hubert TH Low, Jenny Lee, Deshan F Sebaratnam, Ruta Gupta, Michael J Veness, Jonathan Clark and Carsten E Palme
Med J Aust 2023; 218 (1): . || doi: 10.5694/mja2.51786
Published online: 5 December 2022

The DANGER acronym is a simple, evidence‐based aid to identify high risk squamous cell carcinoma

Non‐melanoma skin cancer (NMSC) is the most common group of malignancies diagnosed worldwide.1 Two out of three Australians will develop at least one NMSC before the age of 70 years, with about five NMSC cases diagnosed annually per one invasive cancer of another type.2 NMSC ranges from common lesions such as basal cell carcinoma and cutaneous squamous cell carcinoma (cSCC), collectively termed as keratinocyte carcinoma, to rarer lesions such as Merkel cell carcinoma, atypical fibroxanthoma, dermatofibrosarcoma protuberans, microcystic adnexal carcinoma and angiosarcoma. The most common subtype is basal cell carcinoma, comprising 70–75% of all lesions, followed by cSCC (20–25%) and Merkel cell carcinoma (< 5%).1 Exposure to ultraviolet radiation, particularly during childhood and adolescence, is the predominant aetiological risk factor for developing keratinocyte carcinomas. Therefore, a significant proportion of these malignancies develop on sun‐exposed locations, such as the head and neck, trunk and extremities.3

  • 1 Chris O'Brien Lifehouse, Sydney, NSW
  • 2 University of Sydney, Sydney, NSW
  • 3 Liverpool Hospital, Sydney, NSW
  • 4 University of New South Wales, Sydney, NSW
  • 5 Westmead Hospital, Sydney, NSW
  • 6 Royal Prince Alfred Institute of Academic Surgery, Sydney Local Health District, Sydney, NSW

Competing interests:

No relevant disclosures.

  • 1. Kim RH, Armstrong AW. Nonmelanoma skin cancer. Dermatol Clin 2012; 30: 125–139.
  • 2. Australian Institute of Health and Welfare. Cancer in Australia: an overview. 2008 [Cancer Series no 42; Cat. No. CAN 32].‐4492‐4465‐9175‐7efb886756cb/ca08.pdf.aspx?inline=true (viewed June 2022).
  • 3. Madan V, Lear JT, Szeimies RM. Non‐melanoma skin cancer. Lancet 2010; 375: 673–685.
  • 4. Didona D, Paolino G, Bottoni U, Cantisani C. Non melanoma skin cancer pathogenesis overview. Biomedicines 2018; 6: 6.
  • 5. Brantsch KD, Meisner C, Schönfisch B, et al. Analysis of risk factors determining prognosis of cutaneous squamous‐cell carcinoma: a prospective study. Lancet Oncol 2008; 9: 713–720.
  • 6. Hasmat S, Ebrahimi A, Luk PP, et al. Positive survival trend in metastatic head and neck cutaneous squamous cell carcinoma over four decades: multicenter study. Head Neck 2019; 41: 3826–3832.
  • 7. Ramsay HM, Reece SM, Fryer AA, et al. Seven‐year prospective study of nonmelanoma skin cancer incidence in UK renal transplant recipients. Transplantation 2007; 84: 437–439.
  • 8. Long MD, Herfarth HH, Pipkin CA, et al. Increased risk for non‐melanoma skin cancer in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2010; 8: 268–274.
  • 9. Newlands C, Currie R, Memon A, et al. Non‐melanoma skin cancer: United Kingdom national multidisciplinary guidelines. J Laryngol Otol 2016; 130: S125‐S132.
  • 10. Veness MJ. High‐risk cutaneous squamous cell carcinoma of the head and neck. J Biomed Biotechnol 2007; 2007: 80572.
  • 11. Mooney CP, Clark JR, Shannon K, et al. The significance of regional metastasis location in head and neck cutaneous squamous cell carcinoma. Head Neck 2021; 43: 2705–2711.
  • 12. Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population‐based to a more “personalized” approach to cancer staging. CA Cancer J Clin 2017; 67: 93–99.
  • 13. Stoff B, Salisbury C, Parker D, O'Reilly Zwald F. Dermatopathology of skin cancer in solid organ transplant recipients. Transplant Rev (Orlando) 2010; 24: 172–189.
  • 14. Rhee JS, Matthews BA, Neuburg M, et al. Creation of a quality of life instrument for nonmelanoma skin cancer patients. Laryngoscope 2005; 115: 1178–1185.
  • 15. Rowe DE, Carroll RJ, Day CL. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol 1992; 26: 976–990.
  • 16. Thompson AK, Kelley BF, Prokop LJ, et al. Risk factors for cutaneous squamous cell carcinoma recurrence, metastasis, and disease‐specific death: a systematic review and meta‐analysis. JAMA Dermatol 2016; 152: 419–428.
  • 17. Ross AS, Whalen FM, Elenitsas R, et al. Diameter of involved nerves predicts outcomes in cutaneous squamous cell carcinoma with perineural invasion: an investigator‐blinded retrospective cohort study. Dermatol Surg 2009; 35: 1859–1866.
  • 18. Jennings L, Schmults CD. Management of high‐risk cutaneous squamous cell carcinoma. J Clin Aesthet Dermatol 2010; 3: 39.
  • 19. Gupta A, Veness M, De'Ambrosis B, et al. Management of squamous cell and basal cell carcinomas of the head and neck with perineural invasion. Australas J Dermatol 2016; 57: 3–13.
  • 20. Warner GC, Gandhi M, Panizza B. Slowly progressive cranial nerve palsies. Med J Aust 2006; 184: 641.‐progressive‐cranial‐nerve‐palsies
  • 21. McCord MW, Mendenhall WM, Parsons JT, et al. Skin cancer of the head and neck with clinical perineural invasion. Int J Radiat Oncol Biol Phys 2000; 47: 89–93.
  • 22. Mullen JT, Feng L, Xing Y, et al. Invasive squamous cell carcinoma of the skin: defining a high‐risk group. Ann Surg Oncol 2006; 13: 902–909.
  • 23. Cherpelis B, Marcusen C, Lang P. Prognostic factors for metastasis in squamous cell carcinoma of the skin. Dermatol Surg 2008; 28: 268–273.
  • 24. Thiem DGE, Scharr K, Pabst AM, et al. Facial cutaneous squamous cell carcinoma — microscopic safety margins and their impact on developing local recurrences. J Craniomaxillofac Surg 2020; 48: 49–55.
  • 25. Phillips T, Harris B, Moore M, et al. Pathological margins and advanced cutaneous squamous cell carcinoma of the head and neck. J Otolaryngol Head Neck Surg 2019; 48: 55.


remove_circle_outline Delete Author
add_circle_outline Add Author

Do you have any competing interests to declare? *

I/we agree to assign copyright to the Medical Journal of Australia and agree to the Conditions of publication *
I/we agree to the Terms of use of the Medical Journal of Australia *
Email me when people comment on this article

Online responses are no longer available. Please refer to our instructions for authors page for more information.