Age-related Differences in Tumour Characteristics and Prognostic Factors for Disease Progression in Cutaneous Squamous Cell Carcinoma of the Head and Neck


  • Alet J.G. Leus Department of Dermatology, University Medical Center Groningen, Hanzeplein 1, NL-9700 RB Groningen. The Netherlands
  • Marjolijn S. Haisma
  • Jorrit B. Terra
  • Gilles F.H. Diercks
  • Marloes S. van Kester
  • Gyorgy B. Halmos
  • Emöke Rácz
  • Boukje A.C. van Dijk
  • Boudewijn E.C. Plaat



cutaneous squamous cell carcinoma of the head and neck, aging, metastasis, recurrence, disease progression, elderly


Guidelines for cutaneous squamous cell carcinoma of the head and neck do not take the age of the patient into account, but instead assume equal tumour characteristics and prognostic factors for poor outcome in younger and elderly patients. The aim of this study was to compare tumour characteristics of younger (< 75 years) and elderly (≥ 75 years) patients and identify age-specific risk factors for progression of disease, comprising local recurrence, nodal metastasis and distant metastasis. Patient and tumour characteristics were compared using χ2 or Fisher’s exact tests. Multivariable competing risk analyses were performed to compare risk factors for progression of disease, incorporating the risk of dying before developing progression of disease. A total of 672 patients with primary cutaneous squamous cell carcinoma of the head and neck were retrospectively included. Larger tumour diameter, worse differentiation grade and deeper invasion were observed in older patients. In elderly patients, but not in younger patients, tumour diameter ≥ 40 mm, moderate differentiation grade and an invasion depth ≥ 2 mm were independent risk factors for progression of disease.


Download data is not yet available.


Hollestein LM, de Vries E, Nijsten T. Trends of cutaneous squamous cell carcinoma in the Netherlands: increased incidence rates, but stable relative survival and mortality 1989-2008. Eur J Cancer 2012; 48: 2046-2053.

Holterhues C, Vries E, Louwman MW, Koljenovic S, Nijsten T. Incidence and trends of cutaneous malignancies in the Netherlands, 1989-2005. J Invest Dermatol 2010; 130: 1807-1812.

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. J Am Acad Dermatol 2013; 68: 957-966.

Kallini JR, Hamed N, Khachemoune A. Squamous cell carcinoma of the skin: epidemiology, classification, management, and novel trends. Int J Dermatol 2015; 54: 130-140.

Fears TR, Scotto J. Estimating increases in skin cancer morbidity due to increases in ultraviolet radiation exposure. Cancer Invest 1983; 1: 119-126.

Stang A, Khil L, Kajüter H, Pandeya N, Schmults CD, Ruiz ES, et al. Incidence and mortality for cutaneous squamous cell carcinoma: comparison across three continents. J Eur Acad Dermatol Venereol 2019; 33: 6-10.

Lomas A, Leonardi-Bee J, Bath-Hextall F. A systematic review of worldwide incidence of nonmelanoma skin cancer. Br J Dermatol 2012; 166: 1069-1080.

(NVDV) NV voor D en V. Guideline squamous cell carcinoma of the skin. 2018;

Stratigos AJ, Garbe C, Dessinioti C, Lebbe C, Bataille V, Bastholt L, et al. European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention. Eur J Cancer 2020; 128: 60-82.

Alam M, Ratner D. Cutaneous squamous-cell carcinoma. N Engl J Med 2001; 344: 975-983.

Brantsch KD, Meisner C, Schonfisch B, Trilling B, Wehner-Caroli J, Rocken M, et al. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol 2008; 9: 713-720.

Moore BA, Weber RS, Prieto V, El-Naggar A, Holsinger FC, Zhou X, et al. Lymph node metastases from cutaneous squamous cell carcinoma of the head and neck. Laryngoscope 2005; 115: 1561-1567.

Schmidt C, Martin JM, Khoo E, Plank A, Grigg R. Outcomes of nodal metastatic cutaneous squamous cell carcinoma of the head and neck treated in a regional center. Head Neck 2015; 37: 1808-1815.

Haisma MS, Bras L, Aghdam MA, Terra JB, Plaat BEC, Rácz E, et al. Effect of patient characteristics on treatment decisions regarding keratinocyte carcinoma in elderly patients: a review of the current literature. Acta Derm Venereol 2020: 100: adv00189.

Leus AJG, Frie M, Haisma MS, Terra JB, Plaat BEC, Steenbakkers RJHM, et al. Treatment of keratinocyte carcinoma in elderly patients - a review of the current literature. J Eur Acad Dermatol Venereol 2020; 34: 1932-1943.

de Vries J, Heirman AN, Bras L, Plaat BEC, Rácz E, van Kester MS, et al. Geriatric assessment of patients treated for cutaneous head and neck malignancies in a tertiary referral center: predictors of postoperative complications. Eur J Surg Oncol 2020; 46: 123-130.

Website of the National Institute on Ageing. [cited 2019 Dec 19]. Available from:

Karia PS, Morgan FC, Califano JA, Schmults CD. comparison of tumor classifications for cutaneous squamous cell carcinoma of the head and neck in the 7th vs 8th Edition of the AJCC Cancer Staging Manual. JAMA Dermatol 2018; 154: 175-181.

Green AC, Olsen CM. Cutaneous squamous cell carcinoma: an epidemiological review. Br J Dermatol 2017; 177: 373-381.

Wiser I, Scope A, Azriel D, Zloczower E, Carmel NN, Shalom A. Head and neck cutaneous squamous cell carcinoma clinicopathological risk factors according to age and gender: a population-based study. Isr Med Assoc J 2016; 18: 275-278.

Kounoike N, Akimoto M, Nemoto M, Ishikawa S, Sugimoto T, Takeda A. Surgical treatment of cutaneous squamous cell carcinoma in Japanese patients aged 85 years and older compared with those below 85 years. Kitasato Med J 2015; 45: 118-123.

Lian J, Yue Y, Yu W, Zhang Y. Immunosenescence: a key player in cancer development. J Hematol Oncol 2020; 13: 151.

De Maeyer RPH, Chambers ES. The impact of ageing on monocytes and macrophages. Immunol Lett 2021; 230: 1-10.

Fane M, Weeraratna AT. How the ageing microenvironment influences tumour progression. Nat Rev Cancer 2020; 20: 89-106.

Giunco S, Petrara MR, Bergamo F, Del Bianco P, Zanchetta M, Carmona F, et al. Immune senescence and immune activation in elderly colorectal cancer patients. Aging 2019; 11: 3864-3875.

Berben L, Floris G, Kenis C, Dalmasso B, Smeets A, Vos H, et al. Age-related remodelling of the blood immunological portrait and the local tumor immune response in patients with luminal breast cancer. Clin Transl Immunol 2020; 9: e1184.

Gomes AP, Ilter D, Low V, Endress JE, Fernández-García J, Rosenzweig A, et al. Age-induced accumulation of methylmalonic acid promotes tumour progression. Nature 2020; 585: 283-287.

Serrano M, Blasco MA. Cancer and ageing: convergent and divergent mechanisms. Nat Rev Mol Cell Biol 2007; 8: 715-722.

Ma H, Zhou Z, Wei S, Liu Z, Pooley KA, Dunning AM, et al. Shortened telomere length is associated with increased risk of cancer: a meta-analysis. PLoS One 2011; 6: 1-9.

Rizvi S, Raza ST, Mahdi F. Telomere length variations in aging and age-related diseases. Curr Aging Sci 2014; 7: 161-167.

Anic GM, Sondak VK, Messina JL, Fenske NA, Zager JS, Cherpelis BS, et al. Telomere length and risk of melanoma, squamous cell carcinoma, and basal cell carcinoma. Cancer Epidemiol 2013; 37: 434-439.

Eide MJ, Weinstock MA, Dufresne Jr RG, Neelagaru S, Risica P, Burkholder GJ, et al. Relationship of treatment delay with surgical defect size from keratinocyte carcinoma (basal cell carcinoma and squamous cell carcinoma of the skin). J Invest Dermatol 2005; 124: 308-314.

Renzi C, Mastroeni S, Passarelli F, Mannooranparampil TJ, Caggiati A, Potenza C, et al. Factors associated with large cutaneous squamous cell carcinomas. J Am Acad Dermatol 2010; 63: 404-411.

Alam M, Goldberg LH, Silapunt S, Gardner ES, Strom SS, Rademaker AW, et al. Delayed treatment and continued growth of nonmelanoma skin cancer. J Am Acad Dermatol 2011; 64: 839-848.

Brougham ND, Dennett ER, Cameron R, Tan ST. The incidence of metastasis from cutaneous squamous cell carcinoma and the impact of its risk factors. J Surg Oncol 2012; 106: 811-815.

Sullivan CB, Andresen NS, Kendell N, Al-Qurayshi Z, Pagedar NA. Survival outcomes for advanced cutaneous squamous cell carcinoma of the head and neck. Ann Otol Rhinol Laryngol 2019; 128: 949-955.

Sahovaler A, Krishnan RJ, Yeh DH, Zhou Q, Palma D, Fung K, et al. Outcomes of cutaneous squamous cell carcinoma in the head and neck region with regional lymph node metastasis: a systematic review and meta-analysis. JAMA Otolaryngol Head Neck Surg 2019; 145: 352-360.

Matsuo K, Machida H, Ragab OM, Garcia-Sayre J, Yessaian AA, Roman LD. Patient compliance for postoperative radiotherapy and survival outcome of women with stage I endometrioid endometrial cancer. J Surg Oncol 2017; 116: 482-491.

Badakhshi H, Gruen A, Sehouli J, Budach V, Boehmer D. The impact of patient compliance with adjuvant radiotherapy: a comprehensive cohort study. Cancer Med 2013; 2: 712-717.

Story DA. Postoperative complications in elderly patients and their significance for long-term prognosis. Curr Opin Anaesthesiol 2008; 21: 375-379.




How to Cite

Leus, A. J., Haisma, M. S., Terra, J. B., Diercks, G. F., van Kester, M. S., Halmos, G. B., Rácz, E., van Dijk, B. A., & Plaat, B. E. (2022). Age-related Differences in Tumour Characteristics and Prognostic Factors for Disease Progression in Cutaneous Squamous Cell Carcinoma of the Head and Neck. Acta Dermato-Venereologica, 102, adv00652.