Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of diseases that includes cancers of the oral cavity, pharynx and larynx. Though overall survival differs significantly depending on the primary site of tumor and stage of disease, overall survival at five years is approximately 50%. As the majority of recurrences and mortality occur within 5 years, there is a paucity of literature examining long-term survivorship after this time period. The epidemiology of HNSCC has dramatically changed in the last twenty years with the ongoing rise of human papillomavirus (HPV)-associated oropharyngeal cancer (OPSCC). Patients with HPV+ OPSCC have significantly improved survival when compared to HPV- HNSCC despite presentation at advanced stages. We aim to analyze the long-term survivorship in a population-based cohort for patients with HNSCC with stratification by HPV status.
Methods: Patients alive 5 years post-diagnosis were identified from the Carolina Head and Neck Cancer Study (CHANCE), a population based case-control study. Age-matched controls alive 5 years post reference date were identified and matched in 5-year increments. Date of death was ascertained from the National Death Index. HPV status was ascertained by p16 immunohistochemistry. Non-HPV-associated HNSCCs, defined as all non-oropharyngeal cancers and HPV negative OPSCC, were age-matched 2:1 with controls. HPV-associated OPSCC patients were age-matched 3:1 with controls. Kaplan-Meier curves were constructed and stratified by smoking for cases and controls. Hazard ratios (HRs) were calculated with Cox proportional hazards models and adjusted for private insurance (yes/no), race, and sex.
Results: A total of 342 non-HPV-associated HNSCC patients were age-matched with 684 controls and 121 HPV-associated OPSCC patients were age-matched with 366 controls. For non-HPV-associated HNSCC patients alive 5 years post-diagnosis, ten-year survival was 63.6% (95% CI 58.0%-69.8%) for smokers and 72.1% (95% CI 57.5-90.3%) for non-smokers. Among age-matched controls, survival was 84.6% (95% CI 80.3%-89.1%) and 89.5% (95% CI 86.0%-93.2%) in smokers and non-smokers, respectively. The HR for risk of death in non-HPV-associated HNSCC patients was 2.50 (1.19-5.25) for non-smokers and 3.96 (2.65-5.91) for smokers. For HPV-associated OPSCC patients alive 5 years post-diagnosis, ten-year survival was 83.5% (95% CI 94.3%-99.5%) and 91.3% (95% CI 83.3%-100%) in smokers and non-smokers, respectively. Among age-matched controls, survival was 90.3% (95% CI 85.2%-95.8%) and 96.9% (95 CI 94.3%-99.5%) in smokers and non-smokers, respectively. The HR for death in HPV-associated OPSCCs was 2.69 (0.74-9.86) for non-smokers and 5.64 (2.00-15.89) for smokers.
Conclusions: This is among the first studies to examine long-term HNSCC survivorship with HPV stratification in a population-based setting. We note that survival continues to decline after five years in both HPV-associated and non-HPV-associated HNSCC when compared to age-matched controls. In both non-HPV-associated and HPV-associated HNSCC, smoking plays a significant role in long-term survival. While HPV-positive OPSCC survival remains excellent after five years, HPV-positive OPSCC non-smokers have a decreased survival when compared to controls that approaches that seen in smoking controls. These data provide important prognostic information for patient with HNSCC and underscore the importance of smoking cessation even after successful therapy for HNSCC.