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Updated: Dec 17, 2025

RNAscope for In situ Detection of Transcriptionally Active Human Papillomavirus in Head and Neck Squamous Cell Carcinoma
Published on: March 11, 2014
Non-HPV-Related Head and Neck Squamous Cell Carcinoma in a Young Patient Cohort
Michael I Dougherty1, William Dougherty1, Joshua J Kain2
1Department of Otolaryngology-Head and Neck Surgery, University of Virginia Health System, Charlottesville, VA, USA.
Objectives:
Head and neck squamous cell carcinoma (HNSCC) is rare in patients younger than 40 years. Many practitioners suspect HNSCC is a more aggressive disease in this age group, and perhaps increasing in incidence; however, there are scant and conflicting data to support this assertion. We sought to compare outcomes for young patients with non-human papillomavirus (HPV)-related HNSCC to those of older patients.
Methods:
A retrospective chart review of patients with HNSCC treated from 2004 to 2016 at 2 tertiary referral centers. Patients aged 18 to 40 with p16-negative HNSCC were included in the young patient cohort (n = 59). A randomly selected stage- and subsite-matched cohort aged 55 to 65 was analyzed for comparison (n = 114).
Results:
When considering all patients with HNSCC, patients younger than 40 were more likely to have oral tongue cancer (62.7%) compared to patients age 55 to 65 (16.9%). When an older patient cohort was stage- and subsite-matched to the young patient cohort, there were more never smokers (49.2% vs 17.5% of older patients, P < .01) and females (40.7% vs 24.6% of older patients, P = .028) in the young patient group. The young patient cohort had better average overall survival than the older group (14.4 vs 8.1 years, respectively, P = .02), but similar average disease-free survival (6.2 years vs 6.6 years, respectively, P = .67); 50.9% of young patients had tumors with adverse histologic features versus 42.0% of older patients (P = .28). The young patients demonstrated a superior average conditional survival after recurrence (9.8 years vs 3.2 years for older patients, P < .01).
Conclusions:
Despite the limitations of study design, these data suggest that young patients who develop non-HPV-related HNSCC tend to have similarly aggressive disease, but longer overall survival and better survival after recurrence. These findings may be attributable to better overall health as evidenced by fewer comorbidities.
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