Haitham Mirghani1, Ludovic Lacroix2, Caroline Rossoni3, Roger Sun4, Anne Aupérin3, Odile Casiraghi5, Aude Villepelet6, Roger Lacave7, Gladwys Faucher8, Virginie Marty8, Charles Ferté4, Jean Charles Soria9, Caroline Even4. 1. Department of Head and Neck Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France. Electronic address: haitham.mirghani@gustaveroussy.fr. 2. Translational Research Laboratory and Biobank (AMMICa UMS3655 CNRS /US23 INSERM), Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France; Department of Medical Biology and Pathology, Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France. 3. Department of Biostatistics and Epidemiology, Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France. 4. Department of Head and Neck Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France. 5. Department of Medical Biology and Pathology, Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France. 6. Department of Head and Neck Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France; Tumours Genomic Unit, GHUEP, Tenon Hospital, Assistance Publique - Hôpitaux de Paris, France. 7. Tumours Genomic Unit, GHUEP, Tenon Hospital, Assistance Publique - Hôpitaux de Paris, France. 8. Translational Research Laboratory and Biobank (AMMICa UMS3655 CNRS /US23 INSERM), Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France. 9. Drug Development Department (DITEP), Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France.
Abstract
BACKGROUND: Human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) patients are characterised by a better prognosis than their HPV-negative counterparts. However, this significant survival advantage is not homogeneous and among HPV-positive patients those with a smoking history have a significantly increased risk of oncologic failure. The reason why tobacco consumption impacts negatively the prognosis is still elusive. Tobacco might induce additional genetic alterations leading to a more aggressive phenotype. The purpose of this study was to characterise the mutational profile of HPV-positive OPCs by smoking status. We hypothesise a higher frequency of mutations affecting smokers. METHODS: Targeted next-generation sequencing of 39 genes that are recurrently mutated in head and neck cancers (HNCs) caused by tobacco/alcohol consumption was performed in 62 HPV-driven OPC cases including smokers and non-smokers. RESULTS: The study population included 37 (60%) non-smokers and 25 (40%) smokers. Twenty (32%) patients had no mutation, 14 (23%) had 1 mutation and 28 (45%) had 2 or more mutations. The most commonly mutated genes regardless of tobacco consumption were PIK3CA (19%), MLL2 (19%), TP53 (8%), FAT 1 (15%), FBXW7 (16%), NOTCH1 (10%) and FGFR3 (10%). Mutation rate was not significantly different in smokers compared with non-smokers even when analyses focused on heavy smokers (>20 pack-years vs. <20 pack-years). Similarly, there was no significant difference in mutations patterns according to tobacco consumption. CONCLUSION: In HPV-positive patients, smoking does not increase the mutation rate of genes that are recurrently mutated in traditional HNC. Additional studies are warranted to further describe the molecular landscape of HPV-driven OPC according to tobacco consumption.
BACKGROUND: Human papillomavirus (HPV)-driven oropharyngeal cancer (OPC) patients are characterised by a better prognosis than their HPV-negative counterparts. However, this significant survival advantage is not homogeneous and among HPV-positive patients those with a smoking history have a significantly increased risk of oncologic failure. The reason why tobacco consumption impacts negatively the prognosis is still elusive. Tobacco might induce additional genetic alterations leading to a more aggressive phenotype. The purpose of this study was to characterise the mutational profile of HPV-positive OPCs by smoking status. We hypothesise a higher frequency of mutations affecting smokers. METHODS: Targeted next-generation sequencing of 39 genes that are recurrently mutated in head and neck cancers (HNCs) caused by tobacco/alcohol consumption was performed in 62 HPV-driven OPC cases including smokers and non-smokers. RESULTS: The study population included 37 (60%) non-smokers and 25 (40%) smokers. Twenty (32%) patients had no mutation, 14 (23%) had 1 mutation and 28 (45%) had 2 or more mutations. The most commonly mutated genes regardless of tobacco consumption were PIK3CA (19%), MLL2 (19%), TP53 (8%), FAT 1 (15%), FBXW7 (16%), NOTCH1 (10%) and FGFR3 (10%). Mutation rate was not significantly different in smokers compared with non-smokers even when analyses focused on heavy smokers (>20 pack-years vs. <20 pack-years). Similarly, there was no significant difference in mutations patterns according to tobacco consumption. CONCLUSION: In HPV-positive patients, smoking does not increase the mutation rate of genes that are recurrently mutated in traditional HNC. Additional studies are warranted to further describe the molecular landscape of HPV-driven OPC according to tobacco consumption.
Authors: Xu Qian; Duc T Nguyen; Yue Dong; Branko Sinikovic; Andreas M Kaufmann; Jeffrey N Myers; Andreas E Albers; Edward A Graviss Journal: Int J Biol Sci Date: 2019-05-12 Impact factor: 6.580
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