Trial reportActa oncologica (Stockholm, Sweden)2025
Mutational profile of oropharyngeal squamous cell carcinoma in relation to HPV, tobacco smoking and prognosis with validation in the DAHANCA 19 randomized trial.
Trial report in Acta oncologica (Stockholm, Sweden), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Review
- Human papillomavirus infection and atherosclerotic cardiovascular disease: a comprehensive review of epidemiological evidence, molecular mechanisms, and vaccination-mediated protection.Frontiers in genetics · 2026Review
- BiGART 2025 - the 25th Acta Oncologica Symposium.Acta oncologica (Stockholm, Sweden) · 2025Article
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThis study investigated prognostic biomarkers in oropharyngeal squamous cell carcinoma (OPSCC), with a focus on tumors related to human papillomavirus (HPV) infection and potential molecular effects of tobacco smoking, as smokers with HPV+ OPSCC often have poorer outcomes. PATIENTS/MATERIAL AND
methodsWe first analyzed 56 previously untreated OPSCC patients (exploration cohort), assessing HPV status, gene expression related to hypoxia, tumor subtype, and radiosensitivity, together with next-generation sequencing (NGS) of cancer-related genes. A custom NGS panel was subsequently designed and validated in 162 patients from the DAHANCA 19 randomized controlled trial (RCT), all treated with curative (chemo-)radiotherapy.
resultsIn the exploration cohort (40 HPV+, 79%), the most common molecular events in HPV+ tumors were PIK3CA and ATR mutations and chromosome 3q amplification. ATR and CREBBP mutations occurred more often in heavy smokers (>10 pack-years), but these associations were not confirmed in the DAHANCA 19 cohort. No specific smoking-related mutational signature or link to TP53 mutations was observed. In the DAHANCA 19 cohort, 17 locoregional failures (LRF) occurred among 128 HPV+ patients. No unifying molecular features were identified. However, mutations in NFE2L2 and CASP8, as well as amplifications of 3q genes (BCL6, SOX2), were associated with LRF.
interpretationIn HPV+ OPSCC, only few molecular alterations appear to act as drivers or prognostic biomarkers. Importantly, no molecular features of tobacco smoking exposure were identified, and the mechanism behind the worse prognosis in smokers remains unclear.
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