Martine Froukje van der Kamp1, Gyorgy Bela Halmos2, Victor Guryev3, Peter Laszlo Horvatovich4, Ed Schuuring5, Bernardus Franciscus Augustinus Maria van der Laan6, Bert van der Vegt5, Boudewijn Evert Christiaan Plaat2, Cornelia Johanna Verhoeven2. 1. Department of Otorhinolaryngology and Head and Neck Surgery, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700RB, Groningen, The Netherlands. m.f.van.der.kamp@umcg.nl. 2. Department of Otorhinolaryngology and Head and Neck Surgery, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700RB, Groningen, The Netherlands. 3. European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. 4. Department of Pharmacy, Analytical Biochemistry, University of Groningen, Groningen, The Netherlands. 5. Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 6. Department of Otorhinolaryngology and Head and Neck Surgery, Haaglanden Medical Center, The Hague, The Netherlands.
Abstract
BACKGROUND: In recent clinical practice, an increasing number of elderly patients suffering from head and neck squamous cell carcinoma (HNSCC) of unknown pathophysiology is observed. The majority of HNSCC patients can roughly be divided into three subcategories. First, a small group of young patients who present with variants of genomic aberrations and inheritable diseases like Fanconi anaemia. Second, an increasing population of HPV-related HNSCCs that are regarded as genomic stable tumours with a more favourable prognosis. Though HPV-related tumours used to be more common among younger males, a notable rise in the elderly population is observed. The third subcategory, that of HPV-negative tumours, has been shown to be more heterogeneous with involvement of a variety of oncogenic pathways related to lifestyle factors like smoking and alcohol consumption, often seen in middle-aged males. Some of these pathways could be related to age, such as TP53 alterations, EGFR activation, apoptotic pathway alterations and field cancerization. CONCLUSIONS: In this narrative review, we provide an overview of established and newly discovered age-specific pathophysiological mechanisms underlying HNSCC. We propose a fourth subcategory of patients with a suspected different pathophysiology: elderly (HPV-negative) HNSCC patients without a history of tobacco and alcohol consumption. In this subcategory, carcinogenesis seems to be a multi-step process based on genomic instability, immunosenescence, cell cycle disruption and telomere shortening. To conclude, we discuss suggestions for future research to fill the knowledge gap about age-dependent HNSCC carcinogenesis.
BACKGROUND: In recent clinical practice, an increasing number of elderly patients suffering from head and neck squamous cell carcinoma (HNSCC) of unknown pathophysiology is observed. The majority of HNSCC patients can roughly be divided into three subcategories. First, a small group of young patients who present with variants of genomic aberrations and inheritable diseases like Fanconi anaemia. Second, an increasing population of HPV-related HNSCCs that are regarded as genomic stable tumours with a more favourable prognosis. Though HPV-related tumours used to be more common among younger males, a notable rise in the elderly population is observed. The third subcategory, that of HPV-negative tumours, has been shown to be more heterogeneous with involvement of a variety of oncogenic pathways related to lifestyle factors like smoking and alcohol consumption, often seen in middle-aged males. Some of these pathways could be related to age, such as TP53 alterations, EGFR activation, apoptotic pathway alterations and field cancerization. CONCLUSIONS: In this narrative review, we provide an overview of established and newly discovered age-specific pathophysiological mechanisms underlying HNSCC. We propose a fourth subcategory of patients with a suspected different pathophysiology: elderly (HPV-negative) HNSCC patients without a history of tobacco and alcohol consumption. In this subcategory, carcinogenesis seems to be a multi-step process based on genomic instability, immunosenescence, cell cycle disruption and telomere shortening. To conclude, we discuss suggestions for future research to fill the knowledge gap about age-dependent HNSCC carcinogenesis.
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